Chapter 14

Mende anthe Gee 11I+t-"rt.....,

KEY CONCEPTS

.... Figure 14.1 What principles of inheritance did GregorMendel discover by breeding garden pea plants?

14.1 Mendel used the scientific approach to identifytwo laws of inheritance

14.2 The laws of probability govern Mendelianinheritance

14.3 Inheritance patterns are often more complexthan predicted by simple Mendelian genetics

14.4 Many human traits follow Mendelian patternsof inheritance

r;;;::~~~rom the Deck of Genes

If you happened to see a woman with bright purple hairwalking down the street, you WQuld probablyconclude thatshe hadn't inherited her striking hair color from either par

ent. Consciously or not, you have transformed a lifetime of observations of hair color and other features into a list of possiblevariations that occur naturally among people. Eyes of brown,blue, green, or gray; hair of black, brown, blond, or red-theseare just a few examples of heritable variations that we may observe among individuals in a population. What are the geneticprinciples that account for the transmission ofsuch traits fromparents to offspring in humans and other organisms?

The explanation of heredity most widely in favor during thelBOOs was the 'blending" hypothesis, the idea that genetic material contributed by the two parents mixes in a manner analogousto the way blue and yellow paints blend to make green. This hypothesis predicts that over many generations, a freely matingpopulation wiU give rise to a uniform population of individuals.However, our everyday observations and the results of breedingexperiments with animals and plants contradict that prediction.The blending hypothesis also fails to explain other phenomenaofinheritance, such as traits reappearing after skippingageneration.

An alternative to the blending model is a "particulate" hypothesis of inheritance: the gene idea. According to this model,

parents pass on discrete heritable units-genes-that retaintheir separate identities in offspring. An organism's collectionof genes is more like a deck of cards than a pail of paint. Likeplaying cards, genes can be shuffled and passed along, generation after generation, in undiluted form.

Modern genetics had its genesis in an abbey garden, wherea monk named Gregor Mendel documented a particulatemechanism for inheritance. Figure 14.1 shows Mendel (backrow, holding a sprig of fuchsia) with his fellow monks. Mendeldeveloped his theory of inheritance several de<:ades beforechromosomes were observed in the microscope and the significance oftheir behavior was understood. In this chapter, we willstep into Mendel's garden to re-create his experiments and explain how he arrived at his theory of inheritance. We will alsoexplore inheritance patterns more complex than those observed by Mendel in garden peas. Finally, we will see how theMendelian model applies to the inheritance of human variations, including hereditary disorders such as sickle-cell disease.

r:'~~;:~U:~· ~he scientificapproach to identify two lawsof inheritance

Mendel discovered the basic principles of heredity by breeding garden peas in carefully planned experiments. As we retrace his work, you will recognize the key elements of thescientific process that were introduced in Chapter 1.

Mendel's Experimental,Quantitative ApproachMendel grew up on his parents' small farm in a region of Austria that is now part of the Czech Republic. In this agricultural

262

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TECHNIQUE

oExaminedoffspring:all purpleflowers

() Plantedseeds frompod

o Removed stamensfrom purple flower

6 Transferred sperm·bearing pollen fromstamens of whiteflower to eggbearing carpel ofpurple flower

First filialgenerationoffspring(F,)

Parentalgeneration{P}

Whether forcing self-pollination or executing artificial crosspollination, Mendel could always be sure of the parentage ofnew seeds.

Mendel chose to track only those characters that varied be

tween two distinctaltematives. For example, his plants had either

purple flowers or white flowers; there was nothing intermediatebetween these WiO varieties. Had Mendel focused instead oncharacters that varied in a continuum among individualsseed weight, for example-he would not have discovered theparticulate nature of inheritance. (You11learn why later.)

Mendel also made sure that he started his experimentswith varieties that, over many generations ofself-pollination,

APPLICATION By crossing (mating) two true-breeding varietiesof an organism. scientists can study patterns of inheritance In thisexample. Mendel crossed pea plants that varied in flower color,

RESULTS When pollen from awhite flower was trans-ferred to a purple flower, the first-generation hybrids all had purpleflowers, The result was the same for the reciprocal cross, which involved the transfer of pollen from purple flowers to white flowers.

• ~'4.2

Crossing Pea Plants

•

area, Mendel and the other children received agricultural training in school along with their basic education. As an adolescent, Mendel overcame financial hardship and illness to excelin high school and, later, at the Olmutz Philosophical Institute.

In 1843, at the age of21, Mendel entered an Augustinian

monastery, a reasonable choice at that time for someone whovalued the life ofthe mind. He considered becoming a teacherbut failed the necessary examination. In 1851, he left themonastery to pursue two years of study in physics and chemistry at the University of Vienna. These were very importantyears for Mendel's development as a scientist, in large part dueto the strong influence of two professors. One was the physicist Christian Doppler, who encouraged his students to learnscience through experimentation and trained Mendel to usemathematics to help explain natural phenomena. The otherwas a botanist named Franz Unger, who aroused Mendel's interest in the causes of variation in plants. The instructionMendel received from these two mentors later played a criti

cal role in his experiments with garden peas.After attending the university, Mendel returned to the

monastery and was assigned to teach at a local school, whereseveral other instructors were enthusiastic about scientific research. In addition, his fellow monks shared a long-standingfascination with the breeding of plants. The monastery therefore provided fertile soil in more ways than one for Mendel'sscientific endeavors. Around 1857, Mendel began breedinggarden peas in the abbey garden to study inheritance. Although the question of heredity had long been a focus of curiosity at the monastery, Mendel's fresh approach allowed himto deduce principles that had remained elusive to others.

One reason Mendel probably chose to work with peas is

that they are available in many varieties. For example, one variety has purple flowers, while another variety has white flowers. A heritable feature that varies among individuals, such asflower color, is called a character. Each variant for a character, such as purple or white color for flowers, is termed a trait!

Other advantages of using peas are their short generationtime and the large number ofoffspring from each mating. Furthermore, Mendel could strictly control mating betweenplants. The reproductive organs of a pea plant are in its flowers, and each pea flower has both pollen-producing organs(stamens) and an egg-bearing organ (carpel). In nature, peaplants usually self-fertilize: Pollen grains from the stamens

land on the carpel ofthe same flower, and sperm released fromthe pollen grains fertilize eggs present in the carpel. To achievecross-pollination (fertilization between different plants),

Mendel removed the immature stamens ofa plant before theyproduced pollen and then dusted pollen from another plantonto the altered flowers (Figure 14.2). Each resulting zygotethen developed into a plant embryo encased in a seed (pea).

• Some geneticists use the terms character and trair synonymously, hut in thishook we distinguish hetweenlhem,

CH"'PH~ fOU~HfN Mendel and the Gene Idea 263

224 white-floweredplants

All plants hadpurple flowers

!

705 purple-floweredplants

PGeneration ,(true-breeding

parents) Purple

jWhite

flowers flowers

F, Generation

(hybrids)

F2Generation

G Mendel, Experiments in plan] hybridizallon,Proceedings of the Nawral Hjsrory Society of Bronn 4:3--47 (1 866).

SOURCE

CONCLUSION The "heritable factor" for the recessive trait(white flowers) had not been destroyed or deleted in the F, generation, but merely masked by the presence of the factor for purple flowers, which is the dominant trait.

RESULTS Both purple-flowered and white-flowered plantsappeared in the F1 generation, in aratio of approximately 3: 1

~In uiWhen F1 hybrid pea plants are allowedto self-pollinate, which traits appearin the F2 generation?

EXPERIMENT Around 1860, in amonastery garden in Brunn,Austria, Gregor Mendel used the character of flower color in peaplants to follow traits through two generations, He crossed truebreeding purpl~flowered plants and white-flowered plants (crossesare symbolized by x), The resulting F1 hybrids were allowed to selfpollinate or were cross-pollinated with other F, hybrids, The F2generation plants were then observed for flower color.

nology, purple flower color is adominant trait and white flower

color is a recessive trait. The reappearance of white-flowered

plants in the F2 generation was evidence that the heritable fac

tor causing white flowers had not been diluted or destroyed by

coexisting with the purple-flower factor in the FI hybrids.Mendel observed the same pattern of inheritance in six

other characters, each represented by m'o distinctly different

_I,'l:fill. If you mated two purple-flowered plants from the Pgeneration, what ratio of traits would you expect to observe inthe offspring? Explain.

The law of Segregation

Ifthe blending model ofinheritancewere correct, the F] hybrids

from a cross between purple-flowered and white-flowered pea

plants would have pale purple flowers, a trait intermediate be

tween those of the P generation. Notice in Figure 14.2 that the

experiment produced a very different result: All the F] offspring

had flowers just as purple as the purple-flowered parents. What

happened to the white-flowered plants' genetic contribution to

the hybrids? Ifit were lost, then the FI plants could produce only

purple-flowered offspring in the F2 generation, But when

Mendel allowed the FI plants to self-pollinate and planted their

seeds, the white-flower trait reappeared in the F2 generation.

Mendel used very large sample sizes and kept accurate

records of his results: 705 of the F2 plants had purple flowers,

and 224 had white flowers. These data fit a ratio of approxi

mately three purple to one white (Figure 14.3). Mendel rea

soned that the heritable factor for white flowers did not

disappear in the FI plants, but was somehow hidden or masked

when the purple-flower factor was present. In Mendel's termi-

had produced only the same variety as the parent plant. Such

plants are said to be true-breeding. For example, a plant

with purple flowers is true-breeding ifthe seeds produced by

self-pollination in successive generations all give rise to

plants that also have purple flowers.

In a typical breeding experiment, Mendel cross-pollinated

m'o contrasting, true-breeding pea varieties-for example,

purple-flowered plants and white-flowered plants (see Figure

14.2). This mating, or crossing, of two true-breeding varieties

is called hybridization, The true-breeding parents are re

ferred to as the P generation (parental generation), and their

hybrid offspring are the f] generation (first filial generation,

the word filial from the Latin word for "son"). Allowing these

F] hybrids to self-pollinate produces an f 2 generation (sec

ond filial generation). Mendel usually followed traits for at

least the P, F"

and F2 generations. Had Mendel stopped his

experiments with the F I generation, the basic patterns of in

heritance would have escaped him.

Mendel was a thorough and enthusiastic researcher. In a letter dated 1867, he wrote, "In 1859 I obtained a very fertile de

scendant with large, tasty seeds from a first generation hybrid.

Since in the following year, its progeny retained the desirable

characteristics and were uniform, the variety was cultivated in

our vegetable garden, and many plants were raised every year

up to 1865:' Mendel's quantitative analysis of the F2 plants from

thousands of genetic crosses like these allowed him to deduce

ty,.·o fundamental principles of heredity, which he called the law

of segregation and the law of independent assortment. A rigor

ous experimentalist, Mendel put these principles to the test

again and again by crossing and self-fertilizing F2 and latergeneration pea plants, as well as by carrying out similar experi

ments on other plants, such as beans.

264 UNIT THREE Genetics

Flower position Axial x Terminal 651:207 3.14:1

f tSeed color Yellow x Green 6,022:2,00 1 3.01:1

The Results of Mendel's F, Crosses for SevenCharacters in Pea Plants

traits (Table 14.1). For example, whenMendel crossed a true-breeding varietythat produced smooth, round pea seedswith one that produced wrinkledseeds, all the FI hybrids produced roundseeds; this is the dominant trait for seedshape. In the F2 generation, 75% of theseeds were round and 25% were wrinkled-a 3:1 ratio, as in Figure 14.3. Nowlet's see how Mendel deduced the law ofsegregation from his experimental results. In the discussion that follows, wewill use modern terms instead of someofthe terms used by Mendel. (For exampie, we'll use "gene" instead of Mendel's"heritable factor.")

T."14.1

Character

Flower color

DominantTrait x

Purple x

RecessiveTrait

White

F2 GenerationDominantRecessive Ratio

705:224 3.15:1

... Figure 14.4 Alleles, alternative versions of a gene.Asomatic cell has two copies of each chromosome (forming ahomologous pair) and thus two alleles of each gene. which may beidentical or different. This figure depicts a homologous pair ofchromosomes in an F1 hybrid pea plant. The chromosome with anallele for purple flowers was inherited from one parent. and that withan allele for white flowers from the other parent.

2.95:1

2.82:1

2.84:1

2.96:1

Homologouspair ofchromosomes

Allele for white flowers

Wrinkled 5,474:1,850

Allele for purple flowers

Dwarf 787:277

Yellow 428:152

Constricted 882:299x

x

x

x

Round

Inflated

Tall

Green

Mendel's Model

Mendel developed a model to explain the Seed shape

3:1 inheritance pattern that he consis-tently observed among the F2 offspring inhis peaexperiments. We describe four re-lated concepts making up this model, the Pod shapefourth of which is the law ofsegregation.

First, alternative versions ofgenes account for variations in inherited charac-ters. The gene for flower color in pea Pod colorplants, for example, exists in two ver-sions, one for purple flowers and theother for white flowers. These alternativeversions of a gene are called alleles Stem length(Figure 14.4). Today, we can relate thisconcept to chromosomes and DNA. Asnoted in Chapter 13, each gene is a se-quence of nucleotides at a specific place,or locus, along a particular chromosome.The DNA at that locus, however, can varyslightly in its nucleotide sequence andhence in its information content. The purple-flower allele andthe white-flower allele are two DNA variations possible at theflower-color locus on one of a pea plant's chromosomes.

Se<ond,foreach character, an organism inherits two alleles,onefrom each parent. Remarkably, Mendel made this deduction without knowing about the role of chromosomes. Recall from Chapter 13 that each somatic cell in a diploidorganism has hvo sets of chromosomes, one set inheritedfrom each parent. Thus, a genetic locus is actually represented twice in a diploid cell, once on each homolog of aspecific pair of chromosomes. The two alleles at a particular locus may be identical, as in the true-breeding plants ofMendel's P generation. Or the alleles may differ, as in the FI

hybrids (see Figure 14.4).

CH"'PTE~ fOURTEEN Mendel and the Gene Idea 265

Useful Genetic Vocabulary

An organism that has a pair of identicalalleles for a character is said to be

homozygous for the gene controllingthat character. In the parental generation in Figure 14.5, the purple pea plantis homozygous for the dominant allele(PP), while the white plant is homozygous for the recessive allele (pp). Homozygous plants "breed true" becauseall of their gametes contain the same allele-either Por p in this example. If we

p

White flowerspp

/'1•

that character-then that allele is present in all gametes.But if different alleles are present, as in the F] hybrids, then50% of the gametes receive the dominant allele and 50% receive the recessive allele.

Does Mendel's segregation model account for the 3: 1 ratiohe observed in the F2 generation ofhis numerous crosses? For

the flower-color character, the model predicts that the nvodifferent alleles present in an FI individual will segregate intogametes such that half the gametes will have the purpleflower allele and halfwill have the white-flower allele. Duringself-pollination, gametes ofeach class unite randomly. An eggwith a purple-flower allele has an equal chance of being fertilized by a sperm with a purple-flower allele or one with awhite-flower allele. Since the same is true for an egg with awhite-flower allele, there are four equally likely combinationsof sperm and egg. Figure 14.5 illustrates these combinationsusing a Punnett square, a handy diagrammatic device for

predicting the allele composition of offspring from a cross bern'een individualsof known genetic makeup, Notice that

we use a capital letter to symbolize adominant allele and a lowercase letterfor a recessive allele. In our example, P isthe purple-flower allele, and p is thewhite-flower allele; the gene itself maybe referred to as the PIp gene.

In the Fz offspring, what color will theflowers be? One-fourth of the plants haveinherited two purple--flower alleles; dearly,these plants will have purple flowers. Onehalf of the F2 offspring have inherited one

purple-flower allele and one white--flowerallele; these plants will also have purpleflowers, the dominant trait. Finally, one-

fourth of the Fz plants have inherited twowhite-flower alleles and will express therecessive trait. Thus, Mendel's model accounts for the 3:1 ratio of traits that he observed in the Fzgeneration.

Sperm fromF] (Pp) plant

o 0

Purple flowersPp

••PP Pp

P

"Pp

P

Purple flQlAlersPP

Eggs fromF1(Pp) plant

p

Appearance:Genetic makeup:

Gametes:

Gametes:

Appearance'Genetic makeup:

This box, a Punnett square, showsall possible combinations of allelesin offspring that result from anF1x F, (Pp x Pp) cross. Each squarerepresents an equally probable productof fertilization. For example, the bottomleft box shows the genetic combinationresulting from a0 egg fertilized bya Q>. sperm.

Each true·breeding plant of theparental generation has identical alleles,PP or pp.

Union of parental gametes producesF1hybrids having a Pp combination.Because the purple·flower allele isdominant. all these hybrids have purpleflowers,

When the hybrid plants producegametes, the two alleles segregate.Half of the gametes receive the Palleleand the other half the p allele,

Gametes (circles) each contain onlyone allele for the flower-color gene,In this case, every gamete produced byone parent has the same allele.

Random combination of the gametesresults in the 3:1 ratio that Mendelobserved in the F1 generation.

.4 Figure 14.5 Mendel's law of segregation. This diagram shows the genetic makeup ofthe generations in Figure 14,3. It illustrates Mendel's model for inheritance of the alleles of asinglegene. Each plant has two alleles for the gene controlling flower color, one allele inherited fromeach parent. To construct a Punnett square that predicts the Fl generation offspring, we list all thepossible gametes from one parent (here, the F, female) along the left side of the square and all thepossible gametes from the other parent (here, the F, male) along the top, The boxes represent theoffspring resulting from all the possible unions of male and female gametes.

Third, if the lwo alleles at a locus differ, then one, tiledominant allele, determines the organism's appearance; tileolher, the recessive allele, has no noticeable effect on the organism's appearance. Accordingly, Mendel's F] plants had pur

ple flowers because the allele for that trait is dominant and theallele for white flowers is recessive.

The fourth and final part of Mendel's model, the law ofsegregation, states that the two alleles for a heritablecharacter segregate (separate) during gamete formationand end up in different gametes, Thus, an egg or a spermgets only one of the two alleles that are present in the somatic cells of the organism making the gamete. In termsof chromosomes, this segregation corresponds to the distribution of the two members of a homologous pair ofchromosomes to different gametes in meiosis (see Figure 13.7).Note that if an organism has identical alleles for a particular character-that is, the organism is true· breeding for


Recessive phenotype,known genotype'

pp

x

Dominant phenotype,unknown genotype:

PPor Pp?

• !'!I!!! 14.7

The Testcross

APPLICATION An organism that exhibits adominant trait.such as purple flowers in pea plants, can be either homozygousfor the dominant allele or heterozygous. To determine the organism's genotype, geneticists can perform a testcross.

TECHNIQUE In a testcross, the individual with the unknowngenotype is crossed with a homozygous Individual expressing there<:essive trait (white flowers in this example), and Punnettsquares are used to predict the possible outcomes.

•

2

l'

}Ratio 1:2: 1

Genotype

pp(homozygous)

PP(homozygous)

Pp(heterozygous)

Pp(heterozygous)

Purple

Purple

Phenotype

Purple

1{ White

Ratio 3:1

3

... Figure 14.6 Phenotype versus genotype. Grouping Floffspring from a cross for flower color according to phenotype resultsin the typical 3: 1 phenotypic ratio. In terms of genotype, however,there are actually two categories of purple-flowered plants, PP(homozygous) and Pp (heterozygous), giving a 1:2: 1 genotypic ratio,

PredictionsIf purple-floweredparent is PP

Sperm

0001

If purple-floweredparent is Pp

Sperm

00••Pp l'p

I/;. offspring purple and'h offspring white

oEggs

o••Pp Pp•Pp

All offspring purple

oEggs

oMatching the results to either prediction iden

tifies the unknown parental genotype (either PP or Pp in thisexample). In this testcross, we transferred pollen from awhiteflowered plant to the carpels of a purple-flowered plant; the opposite (reciprocal) cross would have led to the same results.

RESULTS

make only gametes with the recessive allele (p). The allele inthe gamete contributed by the mystery plant will therefore determine the appearance of the offspring (Figure 14.7). If all theoffspring of the cross have purple flowers, then the purpleflowered mystery plant must be homozygous for the dominantallele, because a PP x pp cross produces all Pp offspring. But ifboth the purple and the white phenotypes appear among the

offspring, then the purple-flowered parent must be heterozygous. The offspring of a Pp x pp cross will have a 1:1 phenotypic ratio. Breeding an organism of unknown genotype with arecessive homozygote is called a testcross because it can revealthe genotype of that organism. The testcross was devised byMendel and continues to be an important tool ofgeneticists.

Suppose we have a "mystery" pea plant that has purple flowers.We cannot tell from its flower color if this plant is homozygous(PP) or heterozygous (Pp) because both genotypes result in thesame purple phenotype. To determine the genotype, we cancross this plant with a white-flowered plant (pp), which will

cross dominant homozygotes with recessive homozygotes,every offspring will have two different alleles-Pp in the caseof the F) hybrids of our flower-color experiment (see Figure14.5). An organism that has two different alleles for a gene

is said to be heterozygous for that gene. Unlike homozygotes, heterozygotes are not true-breeding because theyproduce gametes with different alleles; for example, P- andp-containing gametes are both produced by the FI hybridsof Figure 14.5. As a result, self-pollination of those FI

hybrids produces both purple-flowered and white-floweredoffspring.

Because ofthe different effects ofdominant and recessive alleles, an organism's traits do not always reveal its genetic composition. Therefore, we distinguish between an organism'sappearance or observable traits, called its phenotype, and itsgenetic makeup, its genotype. In the case offlower color in peaplants, PP and Pp plants have the same phenotype (purple) butdifferent genotypes. Figure 14.6 reviews these terms. Notethat "phenotype" refers to physiological traits as well as traits

that relate directly to appearance. For example, there is a peavariety that lacks the normal ability to self-pollinate. This physiological variation (non-self-pollination) is a phenotypic trait.

The Testcross

(H"'PTE~ fOURTEEN Mendel and the Gene Idea 267

Phenotypic ratio 9:3:3:1

Sperm

'I.@ '1·0 '1·0 '1'(0

YJ"

Phenotypic ratio approximately 9:3:3: 1

IIYYRR

101 ~

The alternative hypothesis is that the two pairs ofalleles segre~

gate independently ofeach other. In other words, genes are packaged into gametes in all possible allelic combinations, as long aseach gamete has one allele for each gene. In our example, an FI

plant will produce four classes ofgametes in equal quantities: YR,

Gametes

Sperm

'/i@ '/i8

Phenotypic ratio 3: 1

YyRr

Hypothesis of / \ Hypothesis ofdependent assortment independent assortment

I 0' \

108 Q

'h@Eggs h;::-I--"='-I

'he

. In ui

31S

PGeneration

Predictedoffspring ofFz generation

F1Generation

Predictions

Do the alleles for one character assort into gametes dependentlyor independently of the alleles for a different character?

G. Mendel. Expenments in pI~nl hybfidi2~l[on. Prrxeed,ng5 of the N~lur~1 Hi510ry 5ocietyofBrOnn 4:3-47 (1866)

RESULTS

Suppose Mendel had transferred pollen from an F, plant to the carpel of a plantthat was homozygous recessive for both genes. Set up the cross and draw Punnell squaresthat predict the offspring for both hypotheses. Would this cross have supported the hypothesiSof independent assortment equally well?

EXPERIMENT Gregor Mendel followed the charaders of seed color and seed shapethrough the F1 generation. He crossed a true-breeding plant with yellow-round seeds with atrue-bre€ding plant with green-wrinkled seeds, producing dihybrid F1 plants, Self-pollinationof the F1 dihybrids produced the F2 generation, The two hypotheses (dependent and independent assortment) predict different phenotypic ratios.

CONCLUSION Only the hypothesis of independent assortment predicts the appearanceof two of the observed phenotypes: green-round seeds and yellow·wrinkled seeds (seethe right-hand Punnett square). The alleles for seed color and seed shape sort into gametesindependently of each other.

SOURCE

Mendel derived the law of segregation from experiments inwhich he followed only asing!echaracter, such as flower color. All

the FI progeny produced in his crosses of true-breeding parentswere monohybrids, meaning that theywere heterozygous for one character. Werefer to a cross between such heterozygotes as a monohybrid cross.

Mendel identified his second law ofinheritance by follOWing two charactersat the same time, such as seed color andseed shape. Seeds (peas) may be eitheryellow or green. They also may be eitherround (smooth) or wrinkled. From singlecharacter crosses, Mendel knew that theallele for yellow seeds is dominant (Y)and the allele for green seeds is recessive(y). For the seed-shape character, the al-lele for round is dominant (R), and the allele for wrinkled is recessive (r).

Imagine crossing two true-breedingpea varieties that differ in both of thesecharacters-a cross between a plant withyellow-round seeds (ITRR) and a plantwith green-wrinkled seeds (yyrr). TheFI plants will be dihybrids, individualsheterozygous for two characters (YyRr).But are these two characters transmittedfrom parents to offspring as a package?That is, will the Yand R alleles alwaysstay together, generation after generation? Or are seed color and seed shapeinherited independently? Figure 14.8illustrates how a dihybrid cross, a crossbetween F[ dihybrids, can determinewhich of these two hypotheses is correct.

The F] plants, of genotype YyRr, exhibit both dominant phenotypes, yellowseeds with round shapes, no matterwhich hypothesis is correct. The keystep in the experiment is to see what

happens when F[ plants self-pollinateand produce F2 offspring. If the hybridsmust transmit their alleles in the samecombinations in which the alleles wereinherited from the P generation, thenthe F] hybrids will produce only twoclasses of gametes: YR and yr. This "dependent assortment" hypothesis predicts that the phenotypic ratio of the F2

generation will be 3:1, just as in a monohybrid cross (Figure 14.8, left side).

The law of Independent Assortment


YI; yR, and yr. Ifsperm ofthe four classes fertilize eggs ofthe fourclasses, there will be 16 (4X 4) equally probable ways in which thealleles can combine in the F2 generation, as shown in Figure 14.8,right side. These combinations make up four phenotypic categories with a ratio of 9:3:3: I (nine yellow-round to three greenround to three yel1ow-....rtinkled to one green-wrinkled). WhenMendel did the experiment and classified the F2 offspring. his results were close to the predicted 9'3:3: I phenotypic ratio, supporting the hypothesis that the alIdes for one gene-controllingseed color or seed shape, in this example-are sorted into gametes independentlyofthe alleles ofother genes.

Mendel tested his se\'en pea characters in various dihybridcombinations and always observed a 9"3:3:1 phenotypic ratioin the F2 generation. However, notice in Figure 14.8 that thereis a 3: I phenotypic ratio for each of the two characters if youconsider them separately: three yellow to one green, and threeround to one wrinkled. As far as a single character is concerned, the alleles segregate as ifthis were a monohybrid cross.The results ofMendel's dihybrid experiments are the basis forwhat we now call the law of independent assortment, whichstates that etuh pairofalleles segregates independentlyofeachother pairofalleles duringgameteformation.

Strictly speaking, this law applies only to genes (allele pairs)located on different chromosomes-that is, on chromosomesthat are not homologous. Genes located near each other onthe same chromosome tend to be inherited together and havemore complex inheritance patterns than predicted by the lawof independent assortment (see Chapter IS). All the pea characters Mendel chose for analysis were controlled by genes ondifferent chromosomes (or behaved as though they were)j thissituation greatly simplified interpretation of his multicharac·ter pea crosses. All the examples we consider in the rest of thischapter involve genes located on different chromosomes.

r;~;~::: ~~;~obability governMendelian inheritance

Mendel's laws ofsegregation and independent assortment reflect the same rules of probability that apply to tossing coins,rolling dice, and drawing cards from a deck. The probabilityscale ranges from 0 to I. An event that is certain to occur hasa probability of I, while an event that is certain not to occurhas a probabilityofO. W'ith acoin that has heads on both sides,the probability of tossing heads is I, and the probability oftossing tails is O. \Vith a normal coin, the chance of tossingheads is ~. and the chance of tossing tails is~. The probabilityofdrawing the ace ofspades from a 52-card deck is Xl. Theprobabilities ofall possibleoutcomes for an event must add upto I. \Vith a deck ofcards, the chance of picking a card otherthan the ace ofspades is SYIl.

Tossing a coin illustrates an important lesson about probability. For every toss, the probability of heads is ~. The outcome of any particular toss is unaffected by what hashappened on previous trials. We refer to phenomena such ascoin tosses as independent events. Each toss ofacoin, whetherdone sequentially with one coin or simultaneously with many,is independent ofevery other toss. And like two separate cointosses, the alleles of one gene segregate into gametes independently ofanother gene's alleles (the law ofindependent assortment). Two basic rules of probability can help us predictthe outcome of the fusion ofsuch gametes in simple monohybrid crosses and more complicated crosses.

The Multiplication and Addition RulesApplied to Monohybrid Crosses

1. 1.I;tiW". A pea plant heterozygous for inflatedpods (Ii) is crossed with a plant homozygous for constricted pods (ii). Draw a Punnett square for thiscross. Assume pollen comes from the ii plant.

2. 1.li' WIS. Pea plants heterozygous for flowerposition and stem length (AaTt) are allowed to selfpollinate, and 400 of the resulting seeds are planted.Draw a Punnelt square for this cross. How many offspring would be predicted to have terminal flowers andbedwar~(SeeTable 14.1.)

3. _iM i1IM List the different gametes that couldbe made by a pea plant heterozygous for seed color,seed shape, and pod shape (YyRrli; see Table 14.1).How large a Pun nett square would you need topredict the offspring of a self-pollination of this-trihybrid"?

For suggested ClnswefS. see Appendlll A.

CONCEPT CHECI( 14.1 How do we determine the probability that two or more independent events will occur together in some specific combination? For example, what is the chance that tv.'o coins tossedsimultaneously wilt both land heads up? The multiplicationrule states that to determine this probability, we multiply theprobability of one event (one coin coming up heads) by theprobability of the other event (the other coin coming upheads). By the multiplication rule, then, the probability thatboth coins will land heads up is ~ x ~ = Yo.

Wecan apply the same reasoning to an F. monohybrid cross.\Vith seed shape in pea plants as the heritable character, thegenotype of F1 plants is Rr. Segregation in a heterozygous plantis like flipping a coin: Each egg produced has a ~ chance ofcarrying the dominant allele (R) and a ~ chance ofcarrying the recessive allele (r). The same odds apply to each sperm cellproduced. For a particular F2 plant to ha'-e wrinkled seeds, therecessive trait, both the egg and the sperm that come togethermust carry the r allele. The probability that two ralleles ",'ill. bepresent in gametes at fertilization is found by multiplying ~ (the

(HUnt 'OUlTUN Mmdd and the Gene Idea 269

... Figure 14.9 Segregation of alleles and fertilization aschance events. When a heterozygote (Rr) forms gametes, whether aparticular gamete ends up with an Ror an r is like the toss of a coin. Wecan determine the probability for any genotype among the offspring oftwo heterozygotes by multiplying together the individual probabilities ofan egg and sperm having aparticular allele (R or r in thiS example)

probability that the egg will have an r) x Y.- (the probability that

the sperm will have an r). Thus, the multiplication rule tells usthat the probability of an F2 plant with wrinkled seeds (rr) is Yo(Figure 14.9). Likewise, the probability ofan F2 plant carrying

both dominant alleles for seed shape (RR) is y..To figure out the probability that an F2 plant from a mono

hybrid cross will be heterozygous rather than homozygous,

we need to invoke a second rule. Notice in Figure 14.9 that the

dominant allele can come from the egg and the recessive al

lele from the sperm, or vice versa. That is, F I gametes can

combine to produce Rroffspring in two independent and mu

tually exclusive ways: For any particular heterozygous F2

plant, the dominant allele can come from the egg or the

sperm, but not from both. According to the addition rule, the

probability that anyone of two or more mutually exclusive

events will occur is calculated by adding their individual

probabilities. As we have just seen, the multiplication rule

gives us the individual probabilities that we will now add to

gether. The probability for one possible way of obtaining an

F2 heterozygote-the dominant allele from the egg and the

recessive allele from the sperm-is Y•. The probability for

the other possible way-the recessive allele from the egg and

the dominant allele from the sperm-is also Y. (see Figure 14.9).

Using the rule of addition, then, we can calculate the proba

bility of an F2 heterozygote as Y. + Y. = Y.-.

R,

Segregation ofalleles into eggs, ,

, ,-.', -,

A~ft I

'/>

'I.

Sperm

R,

Segregation ofalleles into sperm

~-, ..- ,,"-' ,I(~

t~

Solving Complex Genetics Problemswith the Rules of Probability

We can also apply the rules of probability to predict the out

come of crosses involving multiple characters. Recall that

each allelic pair segregates independently during gamete for

mation (the law of independent assortment). Thus, a dihybrid

or other multicharacter cross is equivalent to two or more in

dependent monohybrid crosses occurring simultaneously. By

applying what we have learned about monohybrid crosses, we

can determine the probability of specific genotypes occurring

in the F2 generation without having to construct unwieldy

Punnett squares.

Consider the dihybrid cross between YyRr heterozygotes

shown in Figure 14.8. We will focus first on the seed-color

character. For a monohybrid cross of Yy plants, the probabili

ties ofthe offspring genotypes are Y. for YY, Yo for Yy, and Y. for

yy. The same probabilities apply to the offspring genotypes for

seed shape: Y. RR, Yl Rr, and Y. rr. Knowing these probabilities,

we can simply use the multiplication rule to determine the

probability of each of the genotypes in the F2 generation. For

example, the probability of an F2 plant having the rYRR geno

type is Y. (YY) x Y. (RR) = YI •. This corresponds to the upper

left box in the larger Punnett square in Figure 14.8. To give an

other example, the probability of an F2 plant with the YyRRgenotype is Yl (Yy) XY. (RR) = Yr. If you look closely at the

larger Punnett square in Figure 14.8, you will see that 2 of the

16 boxes (11) correspond to the YyRR genotype.

Now let's see how we can combine the multiplication and

addition rules to solve even more complex problems in

Mendelian genetics. For instance, imagine a cross of two pea

varieties in which we track the inheritance ofthree characters.

Suppose we cross a trihybrid with purple flowers and yellow,

round seeds (heterozygous for all three genes) with a plant

with purple flowers and green, wrinkled seeds (heterozygous

for flower color but homozygous recessive for the other two

characters). Using Mendelian symbols, our cross is Pp y)'Rr xPpyyrr. What fraction of offspring from this cross would be

predicted to exhibit the recessive phenotypes for at least twoof the three characters?

To answer this question, we can start by listing all

genotypes that fulfill this condition: ppyyRr, ppYyrr,Ppyyrr, PPyyrr, and ppyyrr. (Because the condition is atleast two recessive traits, it includes the last genotype,

which produces all three recessive traits.) Next, we cal

culate the probability for each of these genotypes result

ing from our PpYyRr x Ppyyrr cross by multiplying

together the individual probabilities for the allele pairs,

just as we did in our dihybrid example. Note that in a

cross involving heterozygous and homozygous allele

pairs (for example, Yy x yy), the probability of heterozy

gous offspring is Yl and the probability of homozygous

offspring is 11. Finally, we use the addition rule to add the


probabilities for all the different genotypes that fulfill thecondition of at least two recessive traits, as shown below.

With practice, you'll be able to solve genetics problems fasterby using the rules of probability than by filling in Punnettsquares.

We cannot predict with certainty the exact numbers ofprogenyofdifferent genotypes resulting from a genetic cross. But therules ofprobabilitygive us the chance ofvarious outcomes. Usually, the larger the samplesize, the closer the results will conformto our predictions. The reason Mendel counted so many offspring from his crosses is that he understood this statistical feature of inheritance and had a keen sense ofthe rules ofchance.

Chance of at least rwo recessive traits

ppyyRrppYyrrPpyyrrPPyyrrppyyrr

'/. (probability ofPpJ x 'I> (W) x 1/, (Rr) = '/..~x~x~ =~6

~x~x~ =~6

~x~x~ =~6

~x~x~ =~6

= 6/'6 or'h

alleles, one completely dominant and the other completely recessive" But these conditions are not met by all heritable characters,and the relationship betweengenotype and phenotype is rarely sosimple. Mendel himself realized that he could not explain themore complicated patterns he observed in crosses involvingother pea characters or other plant species. This does not diminish the utility of Mendelian genetics (also called Mendelism),however, because the basic principles of segregation and independent assortment apply even to more complex patterns of inheritance. In this section, we will extend Mendelian genetics tohereditary patterns that were not reported by Mendel.

Extending Mendelian Geneticsfor a Single Gene

The inheritance ofcharacters determined by asingle gene deviates from simple Mendelian patterns when alleles are notcompletely dominant or recessive, when a particular gene hasmore than two alleles, or when a single gene produces multiple phenotypes. We will describe examples of each of thesesituations in this section.

CONCEPT CHECK 14.2I. For any gene with a dominant allele C and recessive

allele c, what proportions of the offspring from aCC x Cc cross are expected to be homozygous dominant, homozygous recessive, and heterozygous?

2, An organism with the genotype BbDD is mated toone with the genotype BBDd. Assuming independentassortment of these two genes, write the genotypes ofall possible offspring from this cross and use the rulesof probability to calculate the chance ofeach genotype occurring.

3. _MU'I. Three characters (flower color, seedcolor, and pod shape) are considered in a cross between two pea plants (Pp Yyfi x ppYyii). \Vhat fractionofoffspring would be predicted to be homozygousrecessive for at least two of the three characters?

For suggested answers, see Appendix A.

r~~"~":~;:n::~~tterns are oftenmore complex than predictedby simple Mendelian genetics

In the 20th century, geneticists extended Mendelian principlesnot only to diverse organisms, but also to patterns of inheritancemore complex than those described by Mendel. Forthework thatled to his lYlO laws of inheritance, Mendel chose pea plant characters that turn out to have a relatively simple genetic basis: Eachcharacter is determined byone gene, for which there are only two

Degrees of Dominance

Alleles can show different degrees ofdominance and recessiveness in relation to each other. In Mendel's classic pea crosses, theF} offspring always looked like one ofthe two parental varietiesbecause one allele in a pair showed complete dominance overthe other. In such situations, the phenotypesofthe heterozygoteand the dominant homozygote are indistinguishable.

For some genes, however, neither allele is completely dominant, and the F1 hybrids have a phenotype somewhere benveen those of the two parental varieties. This phenomenon,called incomplete dominance, is seen when red snapdragonsare crossed with white snapdragons: All the FI hybrids havepink flowers, as shown in Figure 14.100n the next page. Thisthird phenotype results from flowers ofthe heterozygotes having less red pigment than the red homozygotes (unlike the situation in Mendel's pea plants, where the Pp heterozygotesmake enough pigment for the flowers to be a purple color indistinguishable from that of PP plants).

At first glance, incomplete dominance of either alleleseems to provide evidence for the blending hypothesis of inheritance, which would predict that the red or white traitcould never be retrieved from the pink hybrids. In fact, interbreeding F] hybrids produces F2 offspring with a phenotypicratio of one red to two pink to one white. (Because heterozygotes have a separate phenotype, the genotypic and phenotypic ratios for the F2 generation are the same, 1:2:1.) Thesegregation of the red-flower and white-flower alleles in the

• There is one exception, Geneticists ha\'e found that Mendel's pod·shapecharacter is actually determined by two genes.

(H"'PH~ fOURTEEN Mendel and the Gene Idea 271

The Relationship Between Dominance and PhenotypeWe've now seen that the relative effects ofm'o alleles range fromcomplete dominance of one allele, through incomplete dominance ofeither allele, to codominance ofboth alleles. It is important to understand that an allele is not termed dominant becauseit somehow subdues a recessive allele. Recall that alleles are simply variations in a gene's nucleotide sequence. \VIlen a dominantallele coexists with a recessive allele in a heterozygote, they do notactually interact at all. It is in the pathway from genotype to phenotype that dominance and recessiveness come into play.

To illustrate the relationship between dominance and phenotype, we can use one of the characters Mendel studied-roundversus wrinkled pea seed shape. The dominant allele (round)codes for an enzyme that helps convert an unbranched form ofstarch to a branched form in the seed. The recessive allele (wrinkled) codes for a defective form ofthis enzyme, leading to an accumulation of unbranched starch, which causes excess water toenter the seed by osmosis. Later, when the seed dries, it wrinkles.If a dominant allele is present, no excess water enters the seedand it does not wrinkle when it dries. Onedominant allele resultsin enough of the enzyme to synthesize adequate amounts ofbranched starch, which means dominant homozygotes and heterozygotes have the same phenotype: round seeds.

A closer look at the relationship between dominance andphenotype reveals an intriguing fact: For any character, the ob~

served dominant/recessive relationship of alleles depends onthe level at which we examine phenotype. Tay-Sachs disease,an inherited disorder in humans, provides an example. Thebrain cells ofa child with Tay-Sachs disease cannot metabolizecertain lipids because a crucial enzyme does not work properly. As these lipids accumulate in brain cells, the child beginsto suffer seizures, blindness, and degeneration of motor andmental performance and dies within a few years.

Only children who inherit two copies of the Tay-Sacl1S allele(homozygotes) have the disease. Thus, at the organismal level,the Tay-Sachs allele qualifies as recessive. However, the activitylevel of the lipid-metabolizing enzyme in heterozygotes is intermediate bem'een that in individuals homozygous for the normalallele and that in individuals with Tay-Sachs disease. The intermediate phenotype observed at the biocltemicallevel is characteristic of incomplete dominance ofeither allele. Fortunately, theheterozygote condition does not lead to disease symptoms, apparently because half the normal enzyme activity is sufficient toprevent lipid accumulation in the brain. Extendingouranalysis toyet another level, we find that heterozygous individuals produceequal nwnbers of normal and dysfunctional enzyme molecules.Thus, at the molecular level, the normal allele and the Tay-Sachsallele are codominant. As you can see, whether alleles appear tobe completely dominant, incompletely dominant, or codominantdepends on the level at which the phenotype is analyzed.

dominance. Rather, both M and N phenotypes are exhibited byheterozygotes, since both molecules are present.

Sperm

'Il@'he

gametes produced by the pink-flowered plants confirms thatthe alleles for flower color are heritable factors that maintaintheir identity in the hybrids; that is, inheritance is particulate.

Another variation on dominance relationships between alleles is called codominance; in this variation, the two allelesboth affect the phenotype in separate, distinguishable ways.For example, the human MN blood group is determined bycodominant alleles for two specific molecules located on thesurface of red blood cells, the M and N molecules. A singlegene locus, at which m'o allelic variations are possible, determines the phenotype of this blood group. Individuals homozygous for theM allele (MM) have red blood cells with onlyM molecules; individuals homozygous for the N allele (NN)have red blood cells with only N molecules. But both M and Nmolecules are present on the red blood cells of individuals heterozygous for the M and N alleles (MN). Note that the MNphenotype is not intermediate between the M and N phenotypes, which distinguishes codominance from incomplete

.. Figure 14.10 Incomplete dominance in snapdragoncolor. When red snapdragons are crossed with white ones, the F,hybrids have pink flowers Segregation of alleles into gametes of the F,plants results in an Fz generation with a 1:2: 1 ratio for both genotypeand phenotype, The letter Cwith asuperscript indicates an allele forflower color: CR for red and CW for white.

D Suppose a classmate argues thaI this figure supports the blendinghypothesis for inheritance. What might your classmate say, and

how would you respond)


none

(b) Blood group genotypes and phenotypes. There are sixpossible genotypes, resulting in four different phenotypes,

... Figure 14.11 Multiple alleles for the ABO blood groups.The four blood groups result from different combinations of three alleles.n Based on the surface carbohydrate phenotype in (b), what are the.. dominance relationships among the alleles?

A

o

B

AB

Phenotype(blood group)

***•

Red blood cellappearance

ii

Genotype

cus. An example will help clarify this concept. In mice andmany other mammals, black coat color is dominant to brown.Let's designate Band b as the two alleles for this character. Fora mouse to have brown fur, its genotype must be bb. But thereis more to the story. A second gene determines whether or notpigment will be deposited in the hair. TIle dominant allele,symbolized by C (for color), results in the deposition of eitherblack or brown pigment, depending on the genotype at thefirst locus. But if the mouse is homozygous recessive for thesecond locus (ee), then the coat is white (albino), regardless ofthe genotype at the bIacklbrown locus. In this case, the genefor pigment deposition (Cle) is said to be epistatic to the genethat codes for black or brown pigment (Bib).

What happens if we mate black mice that are heterozygousfor both genes (BbCe)? Although the two genes affect thesame phenotypic character (coat color), they follow the law ofindependent assortment. Thus, our breeding experiment represents an FI dihybrid cross, like those that produced a 9:3:3:1

(a) The three alleles for the ABO blood groups and theirassociated carbohydrates. Each allele codes for an enzymethat may add aspecific carbohydrate (designated by the superscript on the allele and shown as a triangle or circle) to the redblood cell.

Allele Carbohydrate

rio AD.

/8 B a

Only two alleles exist for the pea characters that Mendel studied, but most genes exist in more than two allelic forms. TheABO blood groups in humans, for instance, are determined bythree alleles of a single gene: lA, IB, and i. A person's bloodgroup (phenotype) may be one of four types: A, B, AB, or O.

These letters refer to two carbohydrates-A and B-that maybe found on the surface ofred blood cells. A person's blood cells

may have carbohydrate A (type A blood), carbohydrate B(typeB), both (type AB), or neither (type 0), as shown schematicallyin Figure 14.11. Matching compatible blood groups is criticalfor safe blood transfusions (see Chapter 43).

Multiple Alleles

Frequency of Dominant Alleles Although you might assume that the dominant allele for a particular character would

be more common in a population than the recessive allele forthat character, this is not ne<:essarily the case. For example,

about one baby out of400 in the United States is born with extra fingers or toes, a condition known as polydactyly. Somecases of polydactyly are caused by the presence of a dominantallele. The low frequency of polydactyly indicates that the recessive allele, which results in five digits per appendage, is farmore prevalent than the dominant allele in the population. InChapter 23, you will learn how the relative frequencies ofallelesin a population are affected by natural selection.

Dominance relationships, multiple alleles, and pleiotropy allhave to do with the effects of the alleles of a single gene. We

now consider two situations in which two or more genes areinvolved in determining a particular phenotype.

Epistasis

In epistasis (from the Greek for "standing upon~), a gene at onelocus alters the phenotypic expression of a gene at a second 10-

Pleiotropy

Extending Mendelian Geneticsfor Two or More Genes

So far, we have treated Mendelian inheritance as though each

gene affects only one phenotypic character. Most genes, however, have multiple phenotypic effects, a property calledpleiotropy (from the Greekpleion, more). In humans, for example, pleiotropic alleles are responsible for the multiplesymptoms associated with certain hereditary diseases, such ascystic fibrosis and sickle-cell disease, discussed later in thischapter. In the garden pea, the gene that determines flowercolor also affects the color of the coating on the outer surfaceof the seed, which can be gray or white. Given the intricate

molecular and cellular interactions responsible for an organism's development and physiology, it isn't surprising that a sin

gle gene can affect a number ofcharacteristics in an organism.

CH"'PH~ fOURTEEN Mendel and the Gene Idea 273

'I.-

5 6••43,

~.~AaBbCc AaBbCc

y1fa V8 1/8 1faoeo 00- MOO _

Sperm

l/a Va= ..,

l/aO«J

l/aooe

"" V,MOO

V,-

VaO-l/a_

PhenotypeS: 11f~ II '/~ INumber ofdark·skln alleles: 04 .:3

She<

9

:". Figure 14.12 An example of epistasis. This Punnett squareIllustrates the genotypes and phenotypes prE'dicted for otkpring ofmaungs between two black mICe of genotype BbC(. The 0, gene,whICh IS epistatIC to the BIb gene coding for half pigment, controlswhether or not pigment of any color WIll be deposited in the half.

ratio in Mendel's experiments. Wle can use a Punnettsquare torepresent the genotypes of the F2 offspring (Figure 14.12). Asa result of epistasis, the phenotypic ratio among the F2 offspring is 9 black to 3 brown to 4 white. Other types of epistatic interactions produce different ratios, but all are modifiedversions of9:3:3: 1.

• Figure 14.13 A simplified model for polygenicinheritance of skin color. According to thiS model. threeseparately mhented genes affect the darkness of skin. Theheterozygous IndiVIduals (AaBbCc) represented by the two rectanglesat the top of thiS figure each carry three dark-skin alleles (black cirdes.which represent A. B. or C) and three hght-skln alleles (wflite circles,which represent a, b, or C). The Punnett square shO'NS all the pOSSIblegenetIC combinations in gametes and in offspnng of a large number ofhypothetical matings between these heterozygotes. The results aresummanzed by the phenotypic ratios under the Punnett square.,.I/wlll Make abar graph of the result5, with skin color (number ofdark-skin alleles) along the x-axis and fraction ofoffspring along the y-axis.Drawa rough curve corresponding ro rhe results and discuss whar itshows abour rhe relarive proportions ofdifferent phenorypes among theoffspring.

Polygenic Inheritance

Mendel studied characters that could be classified on aneither-or basis, such as purple versus white flower color. Butfor many characters, such as human skin color and height. aneither-or classification is impossible because the charactersvary in the population along a continuum (in gradations).These are called quantitative characters. Quantitative variation usually indicates polygenic inheritance, an additive effect of two or more genes on a single phenotypic character(the converse of pleiotropy, where a single gene affects severalphenotypic characters).

There is evidence, for instance, that skin pigmentation inhumans is controlled by at least three separately inheritedgenes (probably more, but we will simplify). Let's considerthree genes, ""ith a dark-skin allele for each gene (A, B, or C)contributing one ~unit" ofdarkness to the phenotype and be-

ing incompletely dominant to the other allele (a, b, or c). AnMBBCC person would be very dark, while an aabbcc individual would be very light. An AaBbCc person would have skin ofan intermediate shade. Because the alleles have a cumulativeeffect, the genotypes AaBbCc and AABbcc would make thesame genetic contribution (three units) to skin darkness. ThePunnett square in Figure 14.13 shows all possible genotypesof offspring from a mating between individuals heterozygousfor all three genes. As indicated by the row ofsquares below thePunnell square, there are seven skin-eolor phenotypes thatcould result from this mating. Environmental factors, such asexposure to the sun, also affect the skin-color phenotype.

Nature and Nurture: The EnvironmentalImpact on Phenotype

Another departure from simple Mendelian genetics ariseswhen the phenotype for a character depends on environment

274 UNIT TUH Genetics

'.

Integrating a Mendelian Viewof Heredity and Variation

14.3CONCEPT CHECK


1. Incomplete dominance and epistasis are both termsthat define genetic relationships. What is the most

basic distinction between these terms?2. If a man with type AB blood marries a woman with

type 0 blood, what blood types would you expect intheir children?

3. -m:f.i'iA A rooster with gray feathers is matedwith a hen of the same phenotype. Among their offspring, 15 chicks are gray, 6 are black, and 8 are white.What is the simplest explanation for the inheritanceof these colors in chickens? What phenotypes wouldyou expect in the offspring of a cross between a grayrooster and a black hen?

can we integrate these refinements into a comprehensive theory of Mendelian genetics? The key is to make the transitionfrom the reductionist emphasis on single genes and phenotypic characters to the emergent properties of the organism as

a whole, one of the themes of this book.

The term phenotype can refer not only to specific characters, such as flower color and blood group, but also to anorganism in its entirety-all aspects of its physical appearance, internal anatomy, physiology, and behavior. Similarly, the term genotype can refer to an organism's entiregenetic makeup, not just its alleles for a single genetic locus. In most cases, a gene's impact on phenotype is affected by other genes and by the environment. In thisintegrated view of heredity and variation, an organism'sphenotype reflects its overall genotype and unique environmental history.

Considering all that can occur in the pathway from genotype to phenotype, it is indeed impressive that Mendel coulduncover the fundamental principles governing the transmission of individual genes from parents to offspring.Mendel's two laws, segregation and independent assortment, explain heritable variations in terms of alternativeforms of genes (hereditary "particles," now known as the alleles of genes) that are passed along, generation after generation, according to simple rules of probability. This theoryof inheritance is equally valid for peas, flies, fishes, birds,and human beings-indeed for any organism with a sexuallife cycle. Furthermore, by extending the principles of seg

regation and independent assortment to help explain suchhereditary patterns as epistasis and quantitative characters,we begin to see how broadly Mendelism applies. FromMendel's abbey garden came a theory of particulate inheritance that anchors modern genetics. In the last section ofthis chapter, we will apply Mendelian genetics to human inheritance, with emphasis on the transmission of hereditarydiseases.

•

~JI':.:~~~.~.. .:' ;::.~.···{·..~t'

'<~ ,, '" . ..,'71'".. ~ ...·.·'.l'..•.~' r,•• ,.•..,--~..;.7".••.·r .. -'~~~

......:'.

....:..,;.~:;~."" ....•••>

Over the past several pages, we have broadened our view ofMendelian inheritance by exploring degrees of dominance aswell as multiple alleles, pleiotropy, epistasis, polygenic inheritance, and the phenotypic impact of the environment. How

as well as genotype. A single tree, locked into its inheritedgenotype, has leaves that vary in size, shape, and greenness,depending on exposure to wind and sun. For humans, nutrition influences height, exercise alters build, sun-tanning darkens the skin, and experience improves performance onintelligence tests. Even identical twins, who are genetic equals,accumulate phenotypic differences as a result of their uniqueexperiences.

Whether human characteristics are more influenced bygenes or the environment-nature or nurture-is a very oldand hotly contested debate that we will not attempt to settle

here. We can say, however, that a genotype generally is not associated with a rigidly defined phenotype, but rather with arange of phenotypic possibilities due to environmental influences. This phenotypic range is called the norm of reactionfor a genotype (Figure 14.14). For some characters, such as

the ABO blood group system, the norm of reaction has nobreadth whatsoever; that is, a given genotype mandates a veryspecific phenotype. Other characteristics, such as a person'sblood count of red and white cells, vary quite a bit, dependingon such factors as the altitude, the customary level of physicalactivity, and the presence of infectious agents.

Generally, norms of reaction are broadest for polygenic

characters. Environment contributes to the quantitative nature of these characters, as we have seen in the continuous

variation of skin color. Geneticists refer to such characters asmultifactorial, meaning that many factors, both genetic andenvironmental, collectively influence phenotype.

... Figure 14.14 The effect of environment on phenotype.The outcome of dgenotype lies within its norm of readion, a phenotypicrange that depends on the environment in which the genotype isexpressed. For example. hydrangea flowers of the same genetic varietyrange in color from blue-violet to pink, with the shade and intensity ofcolor depending on the acidity and aluminum content of the soil.


~'~~;~:~~~~raits followMendelian patternsof inheritance

K.y

o Male

o Female

o Affededmale

o Affectedfemale

[}--{)

62J2JMating

DOffspring. In

birth order(first·born on left)

Free earlobe

ww

Ww

Ww

ww

ww

wwm

Ww

Ww ww

Attached earlobe

Ww ww ww Ww

3rd generation(two sisters)

2nd generation(parents, aunts,and uncles)

1st generation(grandparents)

1st generation(grandparents) Ff Ff If Ff

2nd generation(parents, aunts,and uncles) FFor Ff if If Ff Ff If

3rd generation(two sisters)

If FFmFf

(b) Is an attached earlobe a dominant or recessive trait?Tips for pedigree analysis: Notice that the first-born daughterin the third generation has attached earlobes, although both ofher parents lack that trait (they have free earlobes). Such apattern is easily explained if the attached-lobe phenotype is dueto a recessive allele If it were due to a dominant allele, then atleast one parent would also have had the trait.

Widow's peak No widow's peak

(a) Is a widow's peak a dominant or recessive trait?Tips for pedigree analysis: Notice in the third generation thatthe second-born daughter lacks a widow's peak, although bothof her parents had the trait. Such a pattern of inheritancesupports the hypothesis that the trait is due to a dominant allele.If the trait were due to a recessive allele, and both parents hadthe recessive phenotype. then all of their offspring would alsohave the recessive phenotype.

.... Figure 14.15 Pedigree analysis. Each of these pedigrees tracesa trait through three generations of the same family. The two traitshave different inheritance patterns, as seen by analysis of the pedigrees.

Pedigree Analysis

Whereas peas are convenient subjects for genetic research,

humans are not. The human generation span is about 20

years, and human parents produce relatively few offspring

compared to peas and most other species. Even more impor

tant, no one would consider it ethical to ask pairs of humans

to breed so that the phenotypes oftheir offspring could be an~

alyzed! In spite of these constraints, the study of human ge~

neties continues to advance, spurred on by the desire tounderstand our own inheritance. New techniques in molecu~

lar biology have led to many breakthrough discoveries, as wewill see in Chapter 20, but basic Mendelism endures as the

foundation of human genetics.

Unable to manipulate the mating patterns of people, geneti·cists must analyze the results of matings that have already oc·curred. They do so by collecting information about a family'shistory for a particular trait and assembling this informationinto a family tree describing the traits of parents and childrenacross the generations-the family pedigree.

Figure 14.1Sa shows a three-generation pedigree thattraces the occurrence of a pointed contour of the hairline onthe forehead. This trait, called a widow's peak, is due to adom~inant allele, W Because the widow's·peak allele is dominant,all individuals who lack a widow's peak must be homozygousrecessive (ww). The two grandparents with widow's peaksmust have the Ww genotype, since some of their offspring arehomozygous recessive. The offspring in the second generationwho do have widow's peaks must also be heterozygous, be·cause they are the products of Ww x ww matings. The thirdgeneration in this pedigree consists of two sisters. The onewho has a widow's peak could be either homozygous (\\7\\7) orheterozygous (Ww), given what we know about the genotypesof her parents (both Ww).

Figure 14.1Sb is a pedigree of the same family, but thistime we focus on a recessive trait, attached earlobes. We'll usef for the recessive allele and F for the dominant allele, whichresults in free earlobes. As you work your way through thepedigree, notice once again that you can apply what you havelearned about Mendelian inheritance to understand the geno·types shown for the family members.

An important application of a pedigree is to help us calcu·late the probability that a child will have a particular genotypeand phenotype. Suppose that the couple represented in thesecond generation of Figure 14.15 decides to have one morechild. What is the probability that the child will have a widow's


Parents

Normal NormalAa x Aa

spermY

o 0

... Figure 14.16 Albinism: a recessive trait. One of the twosisters shown here has normal coloration; the other is albino. Mostrecessive homozygotes are born to parents who are carriers of thedisorder but themselves have a normal phenotype. the case shown inthe Punnelt square.

D What is the probability that the sister with normal coloration is acarrier of the albinism allele?

dicted to be heterozygous carriers, a %chance. Recessive homozygotes could also result from Aa x aa and aa x aamatings, but if the disorder is lethal before reproductive age orresults in sterility (neither ofwhich is true for albinism), no aa

individuals will reproduce. Even if recessive homozygotes are

able to reproduce, such individuals will still account for amuch smaller percentage ofthe population than heterozygouscarriers (for reasons we will examine in Chapter 23).

In general, genetic disorders are not evenly distributedamong all groups ofpeople. For example, the incidence ofTaySachs disease, which we described earlier in this chapter, isdisproportionately high among Ashkenazic Jews, Jewish people whose ancestors lived in central Europe. In that population, Tay-Sachs disease occurs in one out of 3,600 births, anincidence about 100 times greater than that among non-Jewsor Mediterranean (Sephardic) Jews. This uneven distributionresults from the different genetic histories of the world's peoples during less technological times, when populations were

more geographically (and hence genetically) isolated.\Vhen a disease-causing recessive allele is rare, it is relatively

unlikely that two carriers ofthe same harmful allele will meet andmate. However, if the man and woman are close relatives (for ex

ample, siblings or first cousins), the probability of passing on recessive traits increases greatly. TIlese are called consanguineous("same blood") matings, and they are indicated in pedigrees bydouble lines. Because people with recent common ancestors aremore likely to carry the same recessive alleles than are unrelatedpeople, it is more likely that a mating of close relatives will produce offspring homozygous for recessive traits-includingharmful ones. Such effects can be observed in many types ofdomesticated and zoo animals that have become inbred.

There is debate among geneticists about the extent towhich human consanguinity increases the risk of inherited

AAA,

NormalNormal(carrier)

A,Normal '"(carrier) Albino

Eggs

o

How can we account for the behavior of alleles that cause recessively inherited disorders? Recall that genes code for pro

teins of specific function. An allele that causes a geneticdisorder (let's call it allele a) codes either for a malfunctioning

protein or for no protein at all. In the case of disorders classified as recessive, heterozygotes (Aa) are normal in phenotypebecause one copyofthe normal allele (A) produces a sufficientamount of the specific protein. Thus, a recessively inheriteddisorder shows up only in the homozygous individuals (aa)

who inherit one recessive allele from each parent. Althoughphenotypically normal with regard to the disorder, heterozygotes may transmit the recessive allele to their offspring andthus are called carriers. Figure 14.16 illustrates these ideasusing albinism as an example.

Most people who have recessive disorders are born to parents who are carriers of the disorder but themselves have anormal phenotype, as is the case shown in the Punnett squarein Figure 14.16. A mating between two carriers corresponds toa Mendelian F] monohybrid cross, so the predicted genotypicratio for the offspring is 1AA ; 2 Aa; 1aa. Thus, each child has

a Yo chance of inheriting a double dose of the recessive allele;in the case of albinism, such a child will be albino. From thegenotypic ratio, we also can see that outofthree offspring withthe normal phenotype (one AA plus two Aa), two are pre-

peak? This is equivalent to a Mendelian F] monohybrid cross(Ww x Ww), and thus the probability that a child will inherit adominant allele and have a widow's peak is Y. (y. \VW +VI Ww). What is the probability that the child will have at

tached earlobes? Again, we can treat this as a monohybridcross (Ff x Ff), but this time we want to know the chance that

the offspring will be homozygous recessive (.If). That probability is Yo. Finally, what is the chance that the child will have awidow's peak and attached earlobes? Assuming that the genesfor these two characters are on different chromosomes, the

two pairs of alleles will assort independently in this dihybridcross (WwFf x WwFf). Thus, we can use the multiplicationrule: Y. (chance of widow's peak) x I;. (chance of attached ear

lobes) = ;;'6 (chance of widow's peak and attached earlobes).Pedigrees are a more serious matter when the alleles in

question cause disabling or deadly diseases instead ofinnocuous human variations such as hairline or earlobe configuration. However, for disorders inherited as simple Mendelian

traits, the same techniques of pedigree analysis apply.

The Behavior of Recessive Alleles

Thousands of genetic disorders are known to be inherited assimple recessive traits. These disorders range in severity from

relatively mild, such as albinism (lack of pigmentation, whichresults in susceptibility to skin cancers and vision problems),to life-threatening, such as cystic fibrosis.

Recessively Inherited Disorders


diseases. Many deleterious alleles have such severe effects thata homozygous embryo spontaneously aborts long beforebirth. Still, most societies and cultures have laws or taboos forbidding marriages between close relatives. These rules may

have evolved out of empirical observation that in most populations, stillbirths and birth defects are more common when

parents are closely related. Social and economic factors havealso influenced the development of customs and laws againstconsanguineous marriages.

Cystic Fibrosis

The most common lethal genetic disease in the UnitedStates is cystic fibrosis, which strikes one out ofevery 2,500

people of European descent, though it is much rarer in othergroups. Among people of European descent, one out of 25(4%) are carriers of the cystic fibrosis allele. The normal allele for this gene codes for a membrane protein that functions in the transport of chloride ions between certain cellsand the extracellular fluid. These chloride transport channels are defective or absent in the plasma membranes ofchildren who inherit two recessive alleles for cystic fibrosis.The result is an abnormally high concentration of extracellular chloride, which causes the mucus that coats certaincells to become thicker and stickier than normal. The mu

cus builds up in the pancreas, lungs, digestive tract, andother organs, leading to multiple (pleiotropic) effects, including poor absorption of nutrients from the intestines,chronic bronchitis, and recurrent bacterial infections. Re

cent research indicates that the high concentration of extracellular chloride also contributes to infection by disabling anatural antibiotic made by some body cells. When immunecells come to the rescue, their remains add to the mucus,creating a vicious cycle.

If untreated, most children with cystic fibrosis die beforetheir 5th birthday. But daily doses of antibiotics to prevent in

fection, gentle pounding on the chest to clear mucus fromclogged airways, and other preventive treatments can prolonglife. In the United States, more than half ofthose with cystic fi

brosis now survive into their late 20s or even 30s and beyond.

Sickle·Celi Disease

The most common inherited disorder among people ofAfrican descent is sickle-cell disease, which affects one outof 400 African-Americans. Sickle-cell disease is caused by the

substitution of a single amino acid in the hemoglobin proteinof red blood cells. When the oxygen content of an affected individual's blood is low (at high altitudes or under physicalstress, for instance), the sickle-cell hemoglobin molecules ag

gregate into long rods that deform the red cells into a sickleshape (see Figure 5.22). Sickled cells may clump and clog smallblood vessels, often leading to other symptoms throughoutthe body, including physical weakness, pain, organ damage,


and even paralysis. The multiple effects of a double dose ofthesickle-cell allele are another example of pleiotropy. Regularblood transfusions can ward offbrain damage in children withsickle-cell disease, and new drugs can help prevent or treat

other problems, but there is no cure.

Although two sickle-cell alleles are necessary for an individual to manifest full-blown sickle-cell disease, the presence

of one sickle-cell allele can affect the phenotype. Thus, at theorganismal level, the normal allele is incompletely dominantto the sickle-cell allele. Heterozygotes, said to have sickle-celltrait, are usually healthy, but they may suffer some sickle-cellsymptoms during prolonged periods of reduced blood oxygencontent. At the molecular level, the two alleles are codominant; both normal and abnormal (sickle-cell) hemoglobins aremade in heterozygotes.

About one out of ten African-Americans have sickle-celltrait, an unusually high frequency of heterozygotes for an allele with severe detrimental effects in homozygotes. One ex

planation for this is that a single copy of the sickle-cell allelereduces the frequency and severity of malaria attacks, especially among young children. The malaria parasite spends partof its life cycle in red blood cells (see Figure 28.10), and thepresence of even heterozygous amounts of sickle-cell hemoglobin results in lower parasite densities and hence reducedmalaria symptoms. Thus, in tropical Africa, where infectionwith the malaria parasite is common, the sickle-cell allele isboth boon and bane. The relatively high frequency of AfricanAmericans with sickle-cell trait is a vestige oftheir African roots.

Dominantly Inherited Disorders

Although many harmful alleles are recessive, a numberofhuman disorders are due to dominant alleles. One example isachondroplasia, a form of dwarfism that occurs in one ofevery 25,000 people. Heterozygous individuals have the dwarfphenotype (Figure 14.17). Therefore, all people who are notachondroplastic dwarfs-99.99% of the population-are homozygous for the recessive allele. Like the presence of extrafingers or toes mentioned earlier, achondroplasia is a trait forwhich the recessive allele is much more prevalent than thecorresponding dominant allele.

Dominant alleles that cause a lethal disease are much lesscommon than recessive alleles that do so. All lethal alleles

arise by mutations (changes to the DNA) in cells that produce sperm or eggs; presumably, such mutations occurequally often whether the mutant allele is dominant or recessive. However, if a lethal dominant allele causes the death

of offspring before they mature and can reproduce, the allelewill not be passed on to future generations. (In contrast, alethal recessive allele can be perpetuated from generation togeneration by heterozygous carriers who have normal phenotypes, since only homozygous recessive offspring will havethe lethal disease.)

Sperm

o (})

... Figure 14.17 Achondroplasia: a dominant trait. The lateactor David Rappaport had achondroplasia. a form of dwarfismcaused by a dominant allele (0). The allele might have arisen as amutation in the egg or sperm of a parent or could have beeninherited from an affected parent. as shown for an affected father inthe Punnett square

Huntington's Disease

A lethal dominant allele can escape elimination if it causesdeath only after an individual who carries the allele has reacheda relatively advanced age. By the time the symptoms becomeevident, the individual may have already transmitted thelethal allele to his or her children. For example, Huntington'sdisease, a degenerative disease of the nervous system, iscaused by a lethal dominant allele that has no obvious pheno~typic effect until the individual is about 35 to 45 years old.

Once the deterioration of the nervous system begins, it is irreversible and inevitably fatal. Any child born to a parent whohas the allele for Huntington's disease has a 50% chance of in

heriting the allele and the disorder (see the Punnett square inFigure 14.17). In the United States, this devastating disease afflicts about one in 10,000 people.

Until relatively recently, the onset of symptoms was theonly way to know if a person had inherited the Huntington'sallele. This is no longer the case. By analyzing DNA samplesfrom a large family with a high incidence of the disorder, geneticists tracked the Huntington's allele to a locus near the tipof chromosome 4, and the gene has now been sequenced.This information led to development of a test that can detectthe presence of the Huntington's allele in an individual's

genome. (The methods that make such tests possible arediscussed in Chapter 20.) The availability of this test posesan agonizing dilemma for those with a family history ofHuntington's disease, such as relatives of the folk singer

Woody Guthrie, who died of the disease. Does a person currently in good health benefit by finding out whether he or shehas inherited a fatal and not yet curable disease? Some individuals may want to be tested for the disease before planning

a family, whereas others may decide it would be too stressfulto find out. Clearly, this is a personal decision.

The hereditary diseases we have discussed so far are sometimes described as simple Mendelian disorders because theyresult from abnormality of one or both alleles at a single ge·netic locus. Many more people are susceptible to diseases thathave a multifactorial basis-a genetic component plus a sig·nificant environmental influence. Heart disease, diabetes,cancer, alcoholism, certain mental illnesses such as schizo

phrenia and bipolar disorder, and many other diseases aremultifactorial. In many cases, the hereditary component ispolygenic. For example, many genes affect cardiovascularhealth, making some of us more prone than others to heart attacks and strokes. No matter what our genotype, however, ourlifestyle has a tremendous effect on phenotype for cardiovascular health and other multifactorial characters. Exercise, ahealthful diet, abstinence from smoking, and an ability to handle stressful situations all reduce our risk of heart disease andsome types of cancer.

At present, so little is understood about the genetic con·

tributions to most multifactorial diseases that the best public health strategy is to educate people about the importanceofenvironmental factors and to promote healthful behavior.

Multifactorial Disorders

Counseling Based on Mendelian Geneticsand Probability Rules

Consider the case of a hypothetical couple, john and Carol.Both had a brother who died from the same recessively inherited lethal disease. Before conceiving their first child, John andCarol seek genetic counseling to determine the risk of havinga child with the disease. From the information about their

brothers, we know that both parents of john and both parentsof Carol must have been carriers of the recessive allele. Thus,john and Carol are both products ofAa x Aa crosses, where a

symbolizes the allele that causes this particular disease. Wealso know that John and Carol are not homozygous recessive(aa), because they do not have the disease. Therefore, their

genotypes are either AA or Aa.

Given a genotypic ratio of 1AA :2 Aa : 1aa for offspring ofan Aa x Aa cross, John and Carol each have a %chance of being carriers (Aa). According to the rule of multiplication, the

A preventive approach to simple Mendelian disorders is possible when the risk of a particular genetic disorder can be assessed before a child is conceived or during the early stages ofthe pregnancy. Many hospitals have genetic counselors whocan provide information to prospective parents concernedabout a family history for a specific disease.

Genetic Testing and Counseling

Normal, dd

Parents

DwarfDd

Dd ddDwarf Normal

OJ ddDwarf Normalo

Eggs

o


overall probability of their firstborn having the disorder is Y,

(the chance that John is a carrier) times 7l (the chance thatCarol is a carrier) times Yo (the chance of two carriers having achild with the disease), which equals v... Suppose that Carol and

John decide to have a child-after all, there is an 'h chance thattheir baby will not have the disorder. If, despite these odds, theirchild is born with the disease, then we would know that bothJohn and Carol are, in fact, carriers {Aa genotype). Ifboth Johnand Carol are carriers, there is a Yo chance that any subsequentchild this couple has will have the disease.

When we use Mendel's laws to predict possible outcomesof matings, it is important to remember that each child represents an independent event in the sense that its genotype isunaffected by the genotypes of older siblings. Suppose thatJohn and Carol have three more children, and all three havethe hypothetical hereditary disease. There is only one chancein 64 (Y. x Y. x Yo) that such an outcome will occur. Despitethis run of misfortune, the chance that still another child of

this couple will have the disease remains Yo.

Tests for Identifying Carriers

Because most children with recessive disorders are born toparents with normal phenotypes, the key to accurately as

sessing the genetic risk for a particular disease is determining whether the prospective parents are heterozygouscarriers of the recessive allele. For an increasing number ofheritable disorders, tests are available that can distinguishindividuals of normal phenotype who are dominant homozygotes from those who are heterozygotes. There arenow tests that can identify carriers of the alleles for TaySachs disease, sickle-cell disease, and the most commonform of cystic fibrosis.

These tests for identifying carriers enable people with family histories of genetic disorders to make informed decisionsabout having children. But these new methods for genetic

screening pose potential problems. If confidentiality isbreached, will carriers be stigmatized? \Vill they be deniedhealth or life insurance, even though they themselves arehealthy? \Vill misinformed employers equate ~carrier" with dis

ease? And will sufficient genetic counseling be available to helpa large number of individuals understand their test results? Advances in biotechnology offer possibilities for reducing humansuffering, but not before key ethical issues are resolved.

Fetal Testing

Suppose a couple learns that they are both carriers of theTay-Sachs allele, but they decide to have a child anyway.Tests performed in conjunction with a technique known asanmiocentesiscan determine, beginning at the 14th-16th weekof pregnancy, whether the developing fetLlS has Tay-Sachs disease {Figure 14.18a). To perform this procedure, a physician inserts a needle into the uterus and extracts about 10 mL of


amniotic fluid, the liquid that bathes the fetus. Some geneticdisorders can be detected from the presence of certain chemicalsin the amniotic fluid itself. Tests for other disorders, includingTay·Sachs disease, are performed on cells cultured in the labo·

ratory, descendants of the fetal cells sloughed off into the amniotic fluid. These cultured cells can also be used for karyotypingto identify certain chromosomal defects (see Figure 13.3).

In an alternative technique called chorionic villus sampling(CVS), a physician inserts a narrow tube through the cervixinto the uterus and suctions out a tiny sample of tissue fromthe placenta, the organ that transmits nutrients and fetalwastes between the fetus and the mother (Figure 14.18b).

The cells of the chorionic villi of the placenta, the portionsampled, are derived from the fetus and have the same genotype as the new individual. These cells are proliferating rapidly enough to allow karyotyping to be carried out

immediately. This rapid analysis is an advantage over amniocentesis, in which the cells must be cultured for several weeks

before karyotyping. Another advantage of CVS is that it canbe performed as early as the 8th-10th week of pregnancy.However, CVS is not suitable for tests requiring amnioticfluid. Recently, medical scientists have developed methodsfor isolating fetal cells that have escaped into the mother'sblood. Although very few in number, these cells can be cultured and then tested.

Imaging techniques allow a physician to examine a fetus directly for major anatomical abnormalities. In the ultrasoundtechnique, sound waves are used to produce an image of thefetus by a simple noninvasive procedure. In fetoscopy, a

needle-thin tube containing a viewing scope and fiber optics(to transmit light) is inserted into the uterus.

Ultrasound has no known risk to either mother or fetus,

while the other procedures can cause complications in a smallpercentage of cases. Previously, amniocentesis or CVS for diagnostic testing was generally offered only to women over age35, due to their increased risk of bearing a child with Downsyndrome. In 2007, however, reassessment of the risks andpossible benefits led to a change in the recommended practice, and now such testing is offered to all pregnant women. Ifthe fetal tests reveal a serious disorder, the parents face the difficult choice ofterminating the pregnancy or preparing to carefor a child with a genetic disorder.

Newborn Screening

Some genetic disorders can be detected at birth by simpletests that are now routinely performed in most hospitals inthe United States. One common screening program is forphenylketonuria (PKU), a recessively inherited disorder thatoccurs in about one out of every 10,000 to 15,000 births in

the United States. Children with this disease cannot properly metabolize the amino acid phenylalanine. This compound and its by-product, phenylpyruvate, can accumulate

I. Beth and Tom each have a sibling with cystic fibrosis,but neither Beth nor Tom nor any of their parentshave the disease. Calculate the probability that if thiscouple has a child, the child will have cystic fibrosis.What would be the probability if a test revealed thatTom is a carrier but Beth is not?

2. Joan was born with six toes on each foot, a dominanttrait called polydactyly. Two of her five siblings andher mother, but not her father, also have extra digits.What is Joan's genotype for the number-of-digitscharacter? Explain your answer. Use D and d to symbolize the alleles for this character.

3. _i,illfnl. What would you suspect if Peter was

born with polydactyly, but neither of his biologicalparents had extra digits?


to toxic levels in the blood, causing mental retardation.However, if the deficiency is detected in the newborn, a special diet low in phenylalanine will usually allow normal development and prevent retardation. Unfortunately, very fewother genetic disorders are treatable at the present time.

Screening of newborns and fetuses for serious inheriteddiseases, tests for identifying carriers, and genetic counselingall rely on the Mendelian model of inheritance. We owe the"gene idea~ -the concept of particulate heritable factorstransmitted according to simple rules of chance-to the elegant quantitative experiments ofGregor Mendel. The importance of his discoveries was overlooked by most biologistsuntil early in the 20th century, several decades after his findings were reported. In the next chapter, you will learn howMendel's laws have their physical basis in the behavior ofchromosomes during sexual life cycles and how the synthesisof Mendelism and a chromosome theory of inheritance catalyzed progress in genetics.

CONCEPT CHECK 14.4

Amnioticfluidwithdrawn

Fetus __~~y

Placenta,__'ai

GAsampleofamniotic fluid canbe taken starting atthe 14th to 16thweek of pregnancy

Centrifugation

Placenta Chorionic villi

G Asample of chorionic ~illus

tissue can be taken as early asthe 8th to 10th week ofpregnancy.

Fetus

,:---Suction tubeinserted throughcervix

e Karyotyping and biochemicaltests can be performed on thefetal cells immediately, providing results within a day or so.

'FetalcellsSe~eral

•

Biochemicaltests

hours

III_IIIIIII Se~eral

hoursKaryotyping

Se~eral

hours

•

Se~eral

weeks

lLweeks

L€) Fetal cells must be culturedfor se~eral weeks to obtainsufficient numbers forkaryotyping.

Fluid-

Fetal "\..cells "\..

e Biochemical tests can beperformed immediately onthe amniotic fluid or lateron the cultured cells

(a) Amniocentesis (b) Chorionic villus sampling (CVS)

... Figure 14.18 Testing a fetus for genetic disorders. Biochemical tests may detect substances associatedwith particular disorders. Karyotyping shows whether the chromosomes of the fetus are normal In number andappearance.

CH"'PH~ fOU~HfN Mendel and the Gene Idea 281

-w·If·• Go to the Study Area at www.masteringbio.(om for BioFlix3-D animations, MP3 Tutors. Videos, Practice Tests. an eBook, and more. Acthity Gregor's Garden

Ai 11111'-14.3

Example

• • • •• • • •• • • ••• • •• ...

ABO blood group alleles

r', /8, ;

bample

S'ckle-<.:ell disease

PP,AIr PP,f.

Deuription

Description

One gene is able to alleamultiple phenotypiccharacters

Heterozygoles: Bothphenotypes expressed

Heterozygous phenotypeInlermediale betwel!nIfle two fJomozygollSphenotypes

In the whole populallon,some genes have morethan two alleles

HeteroZ'f90US phenotypeSdme as that of homoZ'f9ous oomlr'ant

One gene alleas theexpression of another

Degree 01 dominance

Muiliple alleles

Pleiotropy

Complete dominance ofone allele

Incomplete dominance ofeither allele

Epistasos

... Extending Mendelian Genetics for Two or More Genes

Relationship amonggenes

Inheritance patterns are often more complex than

predicted by simple Mendelian genetics (pp. 271-275)

... Extending Mendelian Genetics for a Single Gene

-w·it.•MPJ TUlor Chromosomal Basisof InheritanceAcli\ity Monohybrid CrossAcli\ity Dih~'bridCrossBiology labs On-line l'edigrcelabBiology labs On-line FlyLab

SUMMARY OF KEY CONCEPTS

_'.11111'_ 14.1Mendel used the scientific approach to identify two

laws of inheritance (pp. 262-269)

... Mendel's Experimental, Quantitative Approach In the186Os, Gregor Mendel formulated a theory of inheritancebased on experiments with garden peas, proposing that parents pass on to their offspring discrete genes that retain theiridentity through generations.

... The Law of Segregation Genes have alternative forms, oralleles. In a diploid organism, the two alleles of a gene segregate (separate) during gamete formation; each sperm or eggcarries only one allele of each pair. This law explains the 3: Iratio of F2 phenotypes observed when monohybrids selfpollinate. Each organism inherits one allele for each genefrom each parent. In heterozygotes, the two alleles aredifferent, and expression of one (the dominant allele) masksthe phenotypic effect of the other (the recessive allele).Homozygotes have identical alleles of a given gene and aretrue-breeding.

... The law of Independent Assortment Each pair of alleles(for one gene) segregates into gametes independently of thepair of alleles for any other gene. In a cross between dihybrids(individuals heterozygous for two genes), the offspring havefour phenotypes in a 9:3:3: 1 ratio.

... Nature and Nurture: The Environmental Impact on Phenotype The expression of a genotype can be affected by environmental influences. The phenotypic range of a particulargenotype is called its norm of reaction. Polygenic charactersthat are also influenced by the environment are called multifactorial characters.

... Integrating a Mendelian View of Heredity and VariationAn organism's overall phenotype, including its physical ap-

_ •.11111'-14.2The laws of probability govern Mendelian inheritance

(pp.269-271)

... The Multiplication and Addition Rules Applied to Monohybrid Crosses The multiplication rule states that the probability of a compound event is equal to the product of theindividual probabilities of the independent single events. Theaddition rule states that the probability of an event that canoccur in two or more independent. mutually exclusive ways isthe sum of the individual probabilities.

... Solving Complex Genetics Problems with the Rules ofProbaliility A dihybrid or other multicharacter cross isequivalent to two or more independent monohybrid crossesoccurring simultaneously. [n calculating the chances of thevarious offspring genotypes from such crosses, each characterfirst is considered separately and then the individual probabilities are multiplied.

Polygenic inhenlance A>Ingle phenotypiccharacter i\ alleaed by\VIIo or more genes Aa8bC~~_A~:CC

- .- .- .- .- .- .- .


pearance, internal anatomy, physiology, and behavior, reflectsits overall genotype and unique environmental history. Evenin more complex inheritance patterns, Mendel's fundamentallaws of segregation and independent assortment still apply.

Acti'ity lnwmplete O<:Iminan'e

.',11""-14.4Many human traits follow Mendelian patternsof inheritance (pp. 276-281)

... Pedigree Analysis Family pedigrees can be used to deducethe possible genotypes of individuals and make predictionsabout future offspring. Predictions are usually statistical probabilities rather than certainties.

... Recessively Inherited Disorders Many genetic disordersare inherited as simple recessive traits. Most affected (ho-

mozygous recessive) individuals are children of phenotypically normal, heterozygous carriers.

... Dominantly Inherited Disorders Lethal dominant alleles areeliminated from the population if affected people die before reproducing. Nonlethal dominant alleles and lethal oneS thatstrike relatively late in life are inherited in a Mendelian way.

... Multifactorial Disorders Many human diseases have bothgenetic and environmental components and do not followsimple Mendelian inheritance patterns.

... Genetic Testing and Counseling Using family histories, genetic counselors help couples determine the odds that theirchildren will have genetic disorders. Amniocentesis andchorionic villus sampling can indicate whether a suspectedgenetic disorder is present in a fetus. Other genetic tests canbe performed after birth.

MM§,jf.MIn\'esllgallon How 0<:1 You Diagnose a Geneti' Disorder?

TESTING YOUR KNOWLEDGE

TIPS FOR GENETICS PROBLEMS

I. Write down symbols for the alleles. (These may be given in theproblem.) When represented by single letters, the dominant allele is uppercase and the recessive is lowercase.

2. Write down the possible genotypes. as determined by thephenotype.a. If the phenotype is that of the dominant trait (for

example, purple flowers), then the genotype is eitherhomozygous dominant or heterozygous (PPor Pp, inthis example).

b. If the phenotype is that of the recessive trait. the genotypemust be homozygous recessive (for example, pp).

c. If the problem says "true-breeding," the genotype ishomozygous.

3. Determine what the problem is asking for. Ifasked to do across, write it out in the form [Genotype] x [Genotype1, usingthe alleles you've decided on.

4. To figure out the outcome of a cross, set up a Punnett square.a. Put the gametes of one parent at the top and those of the

other on the left. To determine the allele(s} in each gamete fora given genotype, set up a systematic way to list all thepossibilities. (Remember, each gamete has one allele ofeachgene.) Note that there are 2" possible types of gametes, wheren is the number of gene loci that are heterozygous. Forexample, an individual with genotype AaBhCc wouldproduce 23 = 8 types of gametes. Write the genotypes ofthe gametes in circles above the columns and to the left ofthe rows.

b. Fill in the Punnett square as if each possible sperm werefertilizing each possible egg, making all of the possibleoffspring. In a cross ofAaBhCc x AaBbCc, for example, thePunnett square would have 8 columns and 8 rows, sothere are 64 different offspring; you would know thegenotype of each and thus the phenotype. Countgenotypes and phenotypes to obtain the genotypic andphenotypic ratios.

5. You can use the rules of probability if the Punnett squarewould be too big. (For example, see Genetics Problem 4.) Youcan consider each gene separately (see pp. 270-271).

6. If, instead, the problem gives you the phenotypic ratios of offspring, but not the genotypes of the parents in a given cross,the phenotypes can help you deduce the parents' unknowngenotypes.a. For example, if ~ the offspring have the recessive

phenotype and Mthe dominant, you know that the crosswas between a heterozygote and a homozygous recessive.

b. If the ratio is 3: 1, the cross was between twoheterozygotes.

c. If two genes are involved and you see a 9:3:3:1 ratio in theoffspring, you know that each parent is heterozygous forboth genes. Caution: Don't assume that the reportednumbers will exactly equal the predicted ratios. Forexample, if there are 13 offspring with the dominant traitand 11 with the re<:essive, assume that the ratio is onedominant to one recessive.

7. For pedigree problems. use the tips in Figure 14.15 and belowto determine what kind of trait is involved.a. If parents without the trait have offspring with the trait,

the trait must be recessive and the parents both carriers.b. If the trait is seen in every generation. it is most likely

dominant (see the next possibility, though).c. If both parents have the trait, then in order for it to be

recessive. all offspring must show the trait.d. To determine the likely genotype of a certain individual

in a pedigree. first label the genotypes of all the familymembers you can. Even if some of the genotypes areincomplete. label what you do know. For example, if anindividual has the dominant phenotype, the genotypemust be AA or An; you can write this as A_. Try differentpossibilities to see which fits the results. Use the rules ofprobability to calculate the probability of each possiblegenotype being the correct one.

CHAPTER fOURTEEN Mendel and the Gene Idea 283

GENETICS PROBLEMS

I. Match each term on the left with a statement on the right.

explanation for this genetic situation? Write genotypes for the

parents, gametes, and offspring.

6. In sesame plants, the one-pod condition (P) is dominant to the

three-pod condition (P), and normal leaf (L) is dominant to

wrinkled leaf (f). Pod type and leaf type are inherited inde

pendently. Determine the genotypes for the two parents for all

possible matings producing the following offspring:

a. 318 one-pod, normal leaf and 98 one-pod, wrinkled leaf

b. 323 three-pod, normal leaf and 106 three-pod, wrinkled leaf

c. 401 one-pod, normal leaf

d. 150 one-pod, normal leaf, 147 one-pod, wrinkled leaf, 51three-pod, normal leaf, and 48 three-pod, wrinkled leaf

e. 223 one-pod, normal leaf, 72 one-pod, wrinkled leaf, 76

three-pod, normal leaf, and 27 three-pod, wrinkled leaf

7. A man with type A blood marries a woman with type B blood.

Their child has type 0 blood. \Vhat are the genotypes of theseindividuals? \'<'hat other genotypes, and in what frequencies,

would you expect in offspring from this marriage?

8. Phenylketonuria (PKU) is an inherited disease caused by a re

cessive allele. If a woman and her husband, who are both carri

ers, have three children, what is the probability ofeach of the

following?

a. All three children are of normal phenotype.

b. One or more of the three children have the disease.

c. All three children have the disease.

d. At least one child is phenotypically normal.

(Note: Remember that the probabilities of all possible

outcomes always add up to 1.)

9. The genotype of Fj individuals in a tetrahybrid cross is

AaBbCcDd. Assuming independent assortment of these four

genes, what are the probabilities that F2 offspring will have the

following genotypes?

a. aabbccddb. AaBbCcDdc. AABBCCDDd. AaBBccDde. AaBBCCdd

II. Karen and Steve each have a sibling with sickle-cell disease.

Neither Karen nor Steve nor any of their parents have the dis

ease. and none of them have been tested to see if they have the

sickle-cell trait. Based on this incomplete information, calculate

the probability that if this couple has a child, the child will have

sickle-cell disease.

10. What is the probability that each of the following pairs of par·

ents will produce the indicated offspring? (Assume independent

assortment of all gene pairs.)a. AABBCC x aabbcc ) AaBbCcb. AABbCc x AaBbCc • AAbbCCc. AaBbCc x AaBbCc • AaBbCcd. aaBbCC x AABbcc • AaBbCc

12. In 1981, a stnly black cat with unusual rounded, curled-back

ears was adopted by a family in California. Hundreds of de·scendants of the cat have since been born, and cat fanciers

RecessiveTerminal (a)Dwarf(t)

Wrinkled (r)

Axial (A)Tall (T)

Round (R)

Dominant

Statement

a. Has no effect on phenotype in a

heterozygote

b. A variant for a characterc. Having m-o identical alleles for a gene

d. A cross between individuals

heterozygous for a single character

e. An alternative version ofa genef. Having m-o different alleles for a gene

g. A heritable feature that variesamong individuals

h. An organism's appearance or

observable traitsi. A cross between an individual with an

unknown genotype and ahomozygous recessive individual

j. Determines phenotype in a

heterozygotek. The genetic makeup of an individual

I. A heritable unit that determines acharacter; can exist in different forms

TermGene

Allele

Character

TraitDominant allele

Recessive allele

_Genotype

_ Phenotype

_ Homozygous

_ Heterozygous

Testcross_ Monohybrid cross

2. • ,1/"""1 Two pea plants heterozygous for the characters of

pod color and pod shape are crossed. Draw a Punnett square to

determine the phenotypic nltios of the offspring.

3. In some plants. a true-breeding, red-flowered strain gives all

pink flowers when crossed with a white-flowered strain: CRCR

(red) x CWCW(white) --+ CRCW (pink). If flower position (ax

ial or terminal) is inherited as it is in peas (see Table 14.1),

what will be the ratios of genotypes and phenotypes of the

FI generation resulting from the following cross: axial-red(true-breeding) X terminal-white? What will be the ratios in

the F2 generation?

If a plant that is heterozygous for all three characters isallowed to self-fertilize, what proportion of the offspring

would you expect to be as follows? (Note: Use the rules of

probability instead of a huge Punnett square.)

a. homozygous for the three dominant traits

b. homozygous for the three recessive traits

c. heterozygous for all three characters

d. homozygous for axial and tall, heterozygous for seed shape

5. A black guinea pig crossed with an albino guinea pig produces

12 black offspring. \Vhen the albino is crossed with a secondblack one, 7 blacks and 5 albinos are obtained. \Vhat is the best

4. Flower position, stem length. and seed shape were three char

acters that Mendel studied. Each is controlled by an indepen

dently assorting gene and has dominant and recessive

expression as follows:

CharacterFlower position

Stem length

Seed shape


hope to develop the curlcat into a show breed.Suppose you owned thefirst curl cat and wantedto develop a true-breeding variety. How wouldyou determine whetherthe curl allele is dominant or recessive? How would you obtain true-breeding curlcats? How could you be sure they are true-breeding?

13. Imagine that a newly discovered, recessively inherited diseaseis expressed only in individuals with type 0 blood, althoughthe disease and blood group are independently inherited. Anormal man with type A blood and a normal woman withtype Bblood have already had one child with the disease. Thewoman is now pregnant for a second time. What is the probability that the second child will also have the disease? Assumethat both parents are heterozygous for the gene that causes thedisease.

17. A man has six fingers on each hand and six toes on each foot.His wife and their daughter have the normal number of digits.Extra digits is a dominant trait. What fnlCtion ofthis couple'schildren would be expected to have extra digits?

18. Imagine that you are a genetic counselor, and a couple planningto start a family comes to you for information. Charles wasmarried once before, and he and his first wife had a child withcystic fibrosis. The brother of his current wife, Elaine, died ofcystic fibrosis. \Vhat is the probability that Charles and Elainewill have a baby with cystic fibrosis? (Neither Charles norElaine has cystic fibrosis.)

19. In mice, black color (8) is dominant to white (b). At a differentlocus, a dominant allele (A) produces a band of yellow just below the tip of each hair in mice with black fur. This gives afrosted appearance known as agouti. Expression of the recessive allele (a) results in a solid coat color. If mice that are heterozygous at both loci are crossed, what is the expectedphenotypic ratio of their offspring?

14. In tigers, a recessive allele causes an absence of fur pigmentation (a white tiger) and a cross-eyed condition. If two phenotypically normal tigers that are heterozygous at this locus aremated, what percentage of their offspring will be cross-eyed?What percentage of cross-eyed tigers will be white?

15. In maize (corn) plants, a dominant allele [inhibits kernel color,while the recessive allele i permits color when homozygous. Ata different locus, the dominant allele Pcauses purple kernelcolor, while the homozygous recessive genotype pp causes redkernels. If plants heterozygous at both loci are crossed, whatwill be the phenotypic ratio of the offspring?

16. The pedigree below traces the inheritance of alkaptonuria,a biochemical disorder. Affected individuals, indicated hereby the colored circles and squares, are unable to metabolizea substance called alkapton. which colors the urine andstains body tissues. Does alkaptonuria appear to be causedby a dominant allele or by a recessive allele? Fill in thegenotypes of the individuals whose genotypes can be deduced. What genotypes are possible for each of the otherindividuals?

Daniel Alan Tina

Christopher

For Gm"liCJ Problem5 nmwer5, !iU Appmdix A.

-MH'·. Visit the Study Area at www.masteringbio.com for aPrilctice Test.

EVOLUTION CONNECTION

20. Over the past half century, there has been a trend in the UnitedStates and other developed cOlUltries for people to marry andstart families later in life than did their parents and grandparents.What effects might this trend have on the incidence (frequency)of late·acting dominant lethal alleles in the population?

SCIENTIFIC INQUIRY

21. You are handed a mystery pea plant with tall stems and axialflowers and asked to determine its genotype as quickly as possible. You know that the allele for tall stems (T) is dominant tothat for dwarf stems (t) and that the allele for axial flowers (A)

is dominant to that for terminal flowers (a).

a. \Vhat are all the possible genotypes for your mysteryplant?

b. Describe the one cross you would do, out in your garden.to determine the exact genotype of your mystery plant.

c. \Vhile waiting for the results of your cross, you predict theresults for each pOSSible genotype listed in part a. How doyou do this? Why is this not called "performing a cross"?

d. Explain how the results of your cross and your predictionswill help you learn the genotype of your mystery plant.

SCIENCE, TECHNOLOGY, AND SOCIETY

22. Imagine that one of your parents had Huntington's disease.What is the probability that you, too, will someday manifest thedisease? There is no cure for Huntington's. Would you want tobe tested for the Huntington's allele? Why or why not?

CH"'PTE~ fOURTEEN Mendel and the Gene Idea 285

Chapter 14

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