Chapter 12

Patterns of Inheritance

Early Ideas about Heredity

• People knew that sperm and eggs transmitted information about traits

• Blending theory

• Problem:– Would expect variation to disappear– Variation in traits persists

Gregor Mendel

• 1822-1884• Central European

monk• Ideas published in

1866• Unrecognized until

1900

Mendel’s Research

• Plants

• But mechanisms of heredity are essentially the same for all complex life forms

• Also apply to people and other animals

Pisum sativum

• Common pea plant

• Flowers are either purple or white • Flower position is axil or terminal

• Seed color is yellow or green• Seed shape is round or wrinkled

• Pod shape is inflated or constricted• Pod color is yellow or green

• Stem length is long or short

Genes

• Units of information about specific traits

• Passed from parent to offspring (inherited)

• Has a specific location (locus) on a chromosome

Diploid

• 2n

• Pairs of genes

• Homologous

Mutations

• Alter gene structure

• May change the information about specific traits carried by the gene

Allele

• All the different forms of the same gene are called alleles

• Eye color– B = brown– b = blue– b/= green

True-breeding

• The same allele for a trait is passed on every generation

• Generation 1 = aa

• Generation 2 = aa

• Generation 3 = aa

• Generation 4 = aa

Genetic Hybrid

• The offspring from a cross of two different true-breeding individuals

• Individual 1 = aa

• Individual 2 = AA

• Offspring = Aa

Names of alleles

• AA = homozygous (same)

• aa = homozygous (same)

• Aa = heterozygous (different)

Precedence of alleles

• Dominant – This version of the trait masks all other

versions– Capital letter A, R, S, H, etc..

• Recessive– This version of the trait is masked by the

dominant trait– Small case letter a, r, s, h, etc…

The complete allele name

• AA - homozygous dominant

• aa – homozygous recessive

• Aa – heterozygous

Genotype

• The combination of alleles• RR• Rr• rr• AA• aa• Aa• Etc………

Phenotype

• The trait expressed by the particular combination of alleles

• Tall• Short• Blue• Brown• Curly• Straight• Etc….

Keeping track of alleles

• P = the parent generation

• F1 = the first-generation (offspring of the parents)

• F2 = the second-generation (offspring of the F1 generation)

Monohybrid Crosses

Experimental intercross between

two F1 heterozygotes

AA X aa Aa (F1 monohybrids)

Aa X Aa ?

Probability

The chance that each outcome of a given event will occur is proportional to the number of ways that event can be reached

Mendel’s Monohybrid Cross Results

787 tall 277 dwarf

651 long stem

207 at tip

705 purple 224 white

152 yellow428 green

299 wrinkled882 inflated

6,022 yellow 2,001 green

5,474 round 1,850 wrinkled

F2 plants showed dominant-to-recessive ratio that averaged 3:1

Mendel’s Theory of Segregation

• An individual inherits a unit of information (allele) about a trait from each parent

• During gamete formation, the alleles segregate from each other

Conservation of Chromosomes

• Meiosis produces cells with half the parental number of chromosomes

• Humans = 46 chromosomes

• Egg or sperm = 23 chromosomes

Test Cross

• Individual that shows dominant phenotype is crossed with individual with recessive phenotype

• Examining offspring allows you to determine the genotype of the dominant individual

Dihybrid Cross

Experimental cross between individuals that are homozygous for different

versions of two traits

Independent Assortment

• Mendel concluded that the two “units” for the first trait were to be assorted into gametes independently of the two “units” for the other trait

• Members of each pair of homologous chromosomes are sorted into gametes at random during meiosis

Random Assortment

Independent Assortment

Metaphase I:

Metaphase II:

Gametes:

Tremendous Variation

Number of genotypes possible in

offspring as a result of independent

assortment and hybrid crossing is

2n

(n is the number of gene loci

at which the parents differ)

Dominance Relations

Complete dominance

Incomplete dominance

Codominance

Complete Dominance

• This version of the trait masks all other versions

• RR = red• Rr = red• Rr’ = red• rr = white• r’r’ = sepia

Incomplete Dominance

The heterozygous phenotype is intermediate between the two homozygous phenotypes

Codominance

• Both alleles are phenotypically expressed in heterozygous individuals

Codominance: ABO Blood Types

• Gene that controls ABO type codes for enzyme that dictates structure of a glycolipid on blood cells

• Two alleles (A and B) are codominant when paired

• Third allele (O) is recessive to others

ABO Blood Type:Allele Combinations

Range of genotypes:

Blood types:

AA

AO AB BO

BB

OO

or or

A AB B O

ABO and Transfusions

• Recipient’s immune system will attack blood cells that

have an unfamiliar glycoprotein on surface

• Type AB is universal recipient because it has both A and

B glycoproteins

• Type O is universal donor because it has neither type A

nor type B glycoproteins

Pleiotropy

• Alleles at a single locus may have effects on two or more traits

• Marfan syndrome - Mutation in gene for fibrillin affects skeleton, cardiovascular system, lungs, eyes, and skin

Pleiotropy

• Marfan syndrome - Mutation in gene for fibrillin affects skeleton, cardiovascular system, lungs, eyes, and skin

Epistasis

• Interaction between the products of gene pairs

• Common among genes for hair color in mammals

Coat Color in

Retrievers

Continuous Variation

• A more or less continuous range of small differences in a given trait among individuals

• The greater the number of genes and

environmental factors that affect a trait, the

more continuous the variation in versions

of that trait

Human Variation

• Some human traits occur as a few discrete types– Attached or detached earlobes – Many genetic disorders

• Other traits show continuous variation– Height– Weight– Eye color

Describing Continuous Variation

Temperature Effects on Phenotype

• Rabbit is homozygous for an allele that specifies a heat-sensitive version of an enzyme in melanin-producing pathway

• Melanin is produced in cooler areas of body

Environmental Effects on Plant Phenotype

• Hydrangea macrophylla

• Action of gene responsible for floral color is influenced by soil acidity

• Flower color ranges from pink to blue

Human Genetics

Chromosomes

• Autosomes– Pairs of homologous chromosomes are alike

• Length• Shape• Gene sequence

– 22 pairs

• Sex chromosomes– Differ physically– One is shorter than the other– Different genes– 1 pair

Sex Determination

• XX = Female : XY = Male• Y = 330 genes

– One gene (SRY) leads to formation of the primary male reproductive organs (testes)

– If it is absent then the primary female reproductive organs form (ovaries)

• X = 2,062 genes– Some determine sexual traits (body fat, hair)– Most nonsexual traits

Karyotype

• Cells cultured in vitro

• Clochicine stops cell division at metaphase

• Separated from solution

• Added to saline solution

• Stain chromosomes

• Separated / sorted by size

What Mendel Didn’t Know

• Crossovers– Physical exchange between homologous

chromosomes that takes place during meiosis I. – Re-assortment of alleles in new combinations– AKA Recombination

• Linkages– The physical association of alleles on the same

chromosome

Homologous Chromosomes

Genes

Genes

Homologous Chromosomes

Duplication

Theory of Segregation

• Diploid cells have pairs of genes, on pairs of homologous chromosomes

• The two genes of each pair are separated from each other during meiosis so they end up in different gametes

Segregation

Segregation

Crossing over

The probability that a crossover will disrupt a gene linkage is

proportional to the distance that separates the two loci

Sex Linkage

• Alleles that are carried on the X chromosome

Human Pedigree

Female

Male

Sex Undetermined

Human Pedigree

Does not have trait

Carrier of trait

Has trait

Human Pedigree

Mating

Offspring

Human Pedigrees

• Determine the probability of a gene being passed to offspring

• Abnormality– Deviations from the average condition– Rare or uncommon

• Disorder– Inherited condition that will cause mild to severe

medical problems

• Syndrome– Set of symptoms that characterize a disorder

• Disease– Illness caused by infectious, dietary, or environmental

factors but not by inheritance of mutant genes

Autosomal Recessive

• Albinism• Blue offspring• Cystic fibrosis• Ellis-van Creveld syndrome• Fanconi anemia• Galactosemia• Phenylketonuria• Sickle-cell anemia

NADH Diaphorase Activity in Blue People

• Red blood cells (RBC) from blue people are deficient in NADH diaphorase activity

• Cannot reduce the oxidized iron in methemoglobin (metHb)

• RBC from the parents of blue people (obligate heterozygotes for the blue trait - Bb) do contain some NADH diaphorase activity but not as much as homozygotes (BB) for the normal allele

Genotype metHb in blood diaphorase activity

BB 0.15% 105Bb 0.26 to 1.0% 60bb 10 to 45% 18

Autosomal Dominant

• Achondroplasia• Camptodactyly• Familial hypercholesterolemia• Huntington disease• Marfan syndrome• Polydactyly• Progeria• Neurofibromatosis

Progeria

• The name stems from the Latin and Greek words pro and geraios and means 'early old age'.

• AKA Hutchinson-Gilford syndrome

• Children with progeria age about ten times faster than normal

• These children develop the symptoms of other diseases, which normally occur only in elderly people, at the age of ten or twelve years.

• Children look perfectly normal during their first year of life

• Then symptoms unfold rapidly– Hair loss

– Disappearance of cheek fat with sharpening of facial features

– Diminished growth

– Subcutaneous fat rapidly disappears completely and the skin becomes thin and brownish with the underlying blood vessels clearly visible

– Dental development is also abnormal with delayed shedding of deciduous teeth and early loss of permanent teeth

– A severe and painful arthrosis develops, with thickening of the joints leading to impaired mobility

• Likely cause is a single-letter "misspelling" in the genetic code on a single chromosome

• The gene makes a protein called lamin A, which forms the inner layer of the membrane around a cell's all-important nucleus

• This mutation leaves progeria patients with misshapen nuclear membranes in 50% of their cells, compared with less than 1% of cells from unaffected children

X-linked Recessive

• Androgen insensitivity syndrome

• Color blindness

• Fragile X syndrome

• Hemophilia

• Muscular dystrophies

• X-linked anhidrotic dysplasia

Fragile-X Syndrome

• The most commonly inherited form of mental retardation.

• Called “fragile-X” because there exists a fragile site or gap at the end of the long arm of the X-chromosome in lymphocytes of affected patients when grown in a folate deficient medium

Signs of Fragile-XLong narrow face Prominent ears, jaw, and forehead High arched palate Flat feet Hyperextensible joints Enlarged testicles Mental impairment, ranging from learning disabilities to mental retardation Attention deficit and hyperactivity Unusual speech pattern (fast, fluctuating rate and repetition of sounds) Anxiety and unstable mood Obsessive-compulsive tendencies Autistic-like behaviors or socially engaging and friendly Hand-flapping, hand-biting Aversion to be held or touched Motor delays Seizures Heart murmur

 

Changes in Chromosome Number

• Down syndrome

• Turner syndrome

• Klinefelter syndrome

• XXX syndrome

• XYY syndrome

Klinefelter’s Syndrome• 1 of 1000 men • Lack some male characteristics

– Less hair growth– Lack of frontal baldness

• Have some female characteristics– Breast development– Wider hips– Narrower shoulders

• Reduced sperm development• Delayed motor function• Delayed speech• Delayed maturation development• Muscle development• Increased lethargy

Turner Syndrome• 1 in 2500 females• XO• Female appearance diminished• 98% of all fetuses with Turner syndrome spontaneously abort• Cardiovascular malformations• Short arms and legs• Increased osteoporosis• Kidney abnormalities• Thyroid disorders• Diabetes• Infertility• Cognitive difficulties – particularly with spatial or mathematics

Changes in Chromosome Structure

• Chronic myelogenous leukemia

• Cri-du-chat syndrome

Cri du chat

• 1 in 50,000 live births

• Caused by a deletion on the short arm of chromosome 5

• The name of this syndrome is French for "cry of the cat," referring to the distinctive cry of children with this disorder

• Some people with this disorder have a shortened lifespan, but most have a normal life expectancy

• In 80 percent of the cases, the chromosome carrying the deletion comes from the father's sperm

Symptoms

• High pitched, cat-like cry or weak cry• Low birth weight• Small head• Rounded face• Broad, flattened bridge of the nose• Eyes spaced wide apart• Folds of skin over the eyelids• Abnormalities of the palate, such as an unusually narrow

and high palate• Receding, small chin• Malformations of the ears

Other Problems

• Difficulties with suckling and swallowing• Gastric reflux• Constipation• High rate of infections, such as ear and upper respiratory

tract infections• Poor muscle tone• Eye problems, such as a squint (strabismus)• Hearing loss• Deformities of the skeleton, such as curvature of the

spine (scoliosis)• Hernias• Heart and kidney problems