NOTES: Ch 15 - Chromosomes,

Sex Determination

& Sex Linkage

Overview: Locating Genes

on Chromosomes

● A century ago the relationship between

genes and chromosomes was not obvious

● Today we can show that genes are located

on chromosomes

● The location of a particular gene can be

seen by tagging isolated chromosomes with

a fluorescent dye that highlights the gene

● Mendelian genes have specific loci

(positions) on chromosomes

● It is the chromosomes that undergo

segregation and independent assortment!

The Chromosome Theory of

Inheritance states that:

P Generation

Gametes

Meiosis

Yellow-round

seeds (YYRR)

Fertilization

Green-wrinkled

seeds (yyrr)

All F1 plants produce

yellow-round seeds (YyRr)

Meiosis

Two equally

probable

arrangements

of chromosomes

at metaphase I

Anaphase I

LAW OF INDEPENDENT ASSORTMENT

Metaphase II

Fertilization among the F1 plantsF2 Generation

Gametes

F1 Generation

LAW OF SEGREGATION

Morgan’s Experimental

Evidence: Scientific Inquiry

● The first solid evidence associating a

specific gene with a a specific

chromosome came from Thomas Hunt

Morgan, an embryologist

Morgan’s Choice of Experimental

Organism: Fruit Flies!

● Characteristics that make

fruit flies a convenient

organism for genetic studies:

-They breed at a high rate

-A generation can be bred

every two weeks

-They have only four pairs of

chromosomes

● Morgan noted WILD TYPE, or normal,

phenotypes that were common in the fly

populations

● Traits alternative to the wild type are

called mutant phenotypes

Correlating Behavior of a Gene’s Alleles

with Behavior of a Chromosome Pair

● In one experiment, Morgan mated male flies with

white eyes (mutant) with female flies with red eyes

(wild type)

-The F1 generation all had red eyes

-The F2 generation showed the 3:1 red:white eye

ratio, but only males had white eyes

● Morgan determined that the white-eye mutant

allele must be located on the X chromosome

● Morgan’s finding supported the chromosome

theory of inheritance!

PGeneration

F1

Generation

F2

Generation

PGeneration

F1

Generation

Ova(eggs) Sperm

F2

Generation

Ova(eggs)

Sperm

The Big Question…

● It may be easy to see that genes

located on DIFFERENT chromosomes

assort independently but what about

genes located on the SAME

chromosome?

Thomas Morgan’s Research

● Morgan identified more than 50 genes

on Drosophila’s 4 chromosomes.

● He discovered that many seemed to be

“linked” together

– They are almost always inherited together

& only rarely become separated

● Grouped genes into 4 linkage groups

Morgan’s Conclusion:

● Each chromosome is actually

a group of linked genes

● BUT Mendel’s principle of

independent assortment still

holds true

● It is the chromosomes that

assort independently!!

– Mendel missed this because 6

of the 7 traits he studied were

on different chromosomes.

So…

● If 2 genes are found on the same

chromosome are they linked forever?

– NO!!

● CROSSING OVER during Meiosis can

separate linked genes

Testcross

parents

Parental-type offspring Recombinant offspring

Ova

Sperm

965

Wild type

(gray-normal)

944

Black-

vestigial

206

Gray-

vestigial

185

Black-

normal

Gray body,

normal wings

(F1 dihybrid)

Sperm

Testcross

offspring

Recombination

frequency391 recombinants

2,300 total offspring 100 = 17%=

Ova

Gametes

Replication of

chromosomes

Black body,

vestigial wings

(double mutant)

Replication of

chromosomes

Meiosis I and II:

No new allele

combinations are

produced.

Meiosis I: Crossing

over between b and vg

loci produces new allele

combinations.

Recombinant

chromosomes

Meiosis II: Separation

of chromatids produces

recombinant gametes

with the new allele

combinations.

Gene Maps

● Alfred Sturtevant was a

graduate student working in

Morgan’s lab part-time in 1911

● He hypothesized that the

farther apart 2 genes are on a

chromosome the more likely

they are to be separated by

crossing-over

● The rate of at which linked

genes are separated can be

used to produce a “map” of

distances between genes

Alfred

Sturtevant

1891-1970

Gene Maps

● This map shows the

relative locations of

each known gene

on a chromosome

● A linkage map is a genetic map of a chromosome based on recombination frequencies

● Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency

● Map units indicate relative distance and order, not precise locations of genes

Linkage Maps

Recombinationfrequencies

9% 9.5%

17%

b cn vg

Chromosome

Short

aristaeBlack

body

Cinnabar

eyes

Mutant phenotypes

Vestigial

wings

Brown

eyes

Wild-type phenotypes

Red

eyes

Normal

wings

Red

eyes

Long aristae

(appendages

on head)

Gray

body

104.567.057.548.50

III

I

IVXYII

Sex-linked genes exhibit unique

patterns of inheritance

● In humans and other animals, there is a

chromosomal basis of sex determination

● Human somatic cells

contain 23 pairs of

chromosomes

-22 pairs of autosomes

(same in males &

females)

-1 pair of sex

chromosomes (XX or

XY)

-Females have 2 matching

sex chromosomes: XX

-Males are XY

Inheritance of Sex-Linked Genes● The sex chromosomes

have genes for many

characters unrelated to

sex

● A gene located on either

sex chromosome is

called a SEX-LINKED

gene

● Sex-linked genes follow

specific patterns of

inheritance

Sperm

Ova

Sperm

Ova

Sperm

Ova

● Some disorders caused by recessive alleles

on the X chromosome in humans:

-Color blindness

-Duchenne muscular dystrophy

-Hemophilia

● When a gene is located on the X

chromosome, females receive 2 copies

of the gene, and males receive only 1

copy

– Example: Color-blindness (c) is recessive

to normal vision (C), and it is located on

the X chromosome; hemophilia

EXAMPLE PROBLEM:

● A female heterozygous for normal

vision: (we say she has normal vision,

but is a carrier of the colorblindness

allele)

● A male who is colorblind:

XC Xc

XcY

What is the probability that: a) they will have a son who is colorblind?

b) they will have a daughter who is colorblind?

c) their first son will be colorblind?

d) their first daughter will be carrier?

XC Xc

Xc

Y

XC Xc Xc Xc

XcYXCY

a) 1/4 (25%)

b) 1/4 (25%)

c) 1/2 (50%)

d) 1/2 (50%)

EXAMPLE PROBLEM:

● Hemophilia is a hereditary disease in which the

blood clotting process if defective. Classic

hemophilia results from an abnormal or missing

clotting factor VIII; it is inherited as an X-linked

recessive disorder (h).

● If a man without hemophilia and a woman who

is a carrier of the hemophilia allele have

children, what is the probability that…

XH XhXHY x

what is the probability that:

a) they will have a daughter with hemophilia?

b) they will have a son with hemophilia?

c) their first son will have hemophilia?

d) their first daughter will be a carrier?

XH Xh

XH

Y

XH XH XH Xh

XhYXHY

a) 0/4 (0%)

b) 1/4 (25%)

c) 1/2 (50%)

d) 1/2 (50%)

Pedigree Charts

Queen Victoria’s Legacy in

Royal Families of Europe

X-inactivation in Female

Mammals

● In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development

● If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character

Early embryo:

X chromosomes

Allele for

orange fur

Cell division

and X

chromosome

inactivation

Allele for

black fur

Active X

Inactive X

Inactive X

Black

fur

Orange

fur

Active X

Two cell populations

in adult cat:

Tortoise-shell cats!

(a.k.a. “Torties”)

XBXb

So, what about the Y chromosome?

Alterations of chromosome number

or structure cause some genetic

disorders

● Large-scale chromosomal alterations often

lead to spontaneous abortions

(miscarriages) or cause a variety of

developmental disorders

Abnormal Chromosome Number

● In NONDISJUNCTION, pairs of

homologous chromosomes do not

separate normally during meiosis

● As a result, one gamete receives two of

the same type of chromosome, and

another gamete receives no copy

Meiosis I

Nondisjunction

Meiosis II

Nondisjunction

Gametes

n + 1

Number of chromosomes

Nondisjunction of homologous

chromosomes in meiosis I

n + 1 n – 1 n – 1 n + 1 n – 1 n n

Nondisjunction of sister

chromatids in meiosis I

● Aneuploidy results from the fertilization

of gametes in which nondisjunction

occurred

● Offspring with this condition have an

abnormal number of a particular

chromosome

● a TRISOMIC zygote has three copies

of a particular chromosome

● a MONOSOMIC zygote has only one

copy of a particular chromosome

● Polyploidy is a condition

in which an organism has

more than two complete

sets of chromosomes

Alterations of Chromosome

Structure

● Breakage of a chromosome can lead to four

types of changes in chromosome structure:

-Deletion removes a chromosomal segment

-Duplication repeats a segment

-Inversion reverses a segment within a

chromosome

-Translocation moves a segment from one

chromosome to another

Deletion

Duplication

Inversion

Reciprocal

translocation

A deletion removes a chromosomal

segment.

A duplication repeats a segment.

An inversion reverses a segment

within a chromosome.

A translocation moves a segment

from one chromosome to another,

nonhomologous one.

Human Disorders Due to

Chromosomal Alterations

● Alterations of chromosome number and structure

are associated with some serious disorders

● Some types of aneuploidy appear to upset the

genetic balance less than others, resulting in

individuals surviving to birth and beyond

● These surviving individuals have a set of

symptoms, or syndrome, characteristic of the type

of aneuploidy

Down Syndrome:

● Down Syndrome is an aneuploid condition that results from three copies of chromosome 21

● It affects about one out of every 700 children born in the United States

● The frequency of Down Syndrome increases with the age of the mother

Aneuploidy of Sex Chromosomes

● Nondisjunction of sex chromosomes

produces a variety of aneuploid conditions

● Klinefelter syndrome is the result of an

extra chromosome in a male, producing

XXY individuals

● Monosomy X, called Turner syndrome,

produces X0 females, who are sterile; it is

the only known viable monosomy in humans

Disorders Caused by Structurally

Altered Chromosomes:

● One syndrome, cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5

● A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood

● Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes

Reciprocal

translocation

Normal chromosome 9

Normal chromosome 22

Translocated chromosome 9

Translocated chromosome 22

Philadelphiachromosome