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
The Chromosome Theory of
Inheritance states that:
● Mendelian genes have specific loci
(positions) on chromosomes
● It is the chromosomes that undergo
segregation and independent assortment!
P Generation Yellow-round Green-wrinkled
seeds (YYRR) seeds (yyrr)

Meiosis

Fertilization
Gametes

All F1 plants produce

yellow-round seeds (YyRr)

F1 Generation

Meiosis
LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT
Two equally
probable
arrangements
of chromosomes
at metaphase I

Anaphase I

Metaphase II

Gametes

F2 Generation
Fertilization among the F1 plants
 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!
 P
Generation

F1
Generation

F2
Generation

P
Generation

Ova
(eggs) Sperm

F1
Generation

Ova
(eggs) Sperm

F2
Generation
 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 Gray body, Black body,
parents normal wings vestigial wings
(F1 dihybrid) (double mutant)

Replication of Replication of
chromosomes chromosomes

Meiosis I: Crossing
over between b and vg
loci produces new allele
combinations.

Meiosis I and II:

No new allele
combinations are
produced.

Meiosis II: Separation

of chromatids produces
recombinant gametes Recombinant
with the new allele chromosomes
combinations.
Ova Sperm

Gametes

Ova

Testcross 965 944 206 185

offspring Wild type Black- Gray- Black-
Sperm (gray-normal) vestigial vestigial normal Recombination 391 recombinants
=  100 = 17%
frequency 2,300 total offspring

Parental-type offspring Recombinant offspring

 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 Alfred
crossing-over Sturtevant
● The rate of at which linked 1891-1970
genes are separated can be
used to produce a “map” of
distances between genes
 Gene Maps
● This map shows the
relative locations of
each known gene
on a chromosome
 Linkage Maps
● 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
 Recombination
frequencies

9% 9.5%

17%

b cn vg
Chromosome
 I

X IV
II Y
III

Mutant phenotypes

Short Black Cinnabar Vestigial Brown

aristae body eyes wings eyes

0 48.5 57.5 67.0 104.5

Long aristae Gray Red Normal Red

(appendages body eyes wings eyes
on head)

Wild-type phenotypes
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 Sperm

Ova Ova 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)
X X C c

● A male who is colorblind:

Xc Y
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 X c a) 1/4 (25%)
b) 1/4 (25%)
X c XC Xc Xc Xc
c) 1/2 (50%)

Y X Y X Y
C c
d) 1/2 (50%)
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 X c a) 1/4 (25%)
b) 1/4 (25%)
X c XC Xc Xc Xc
c) 1/2 (50%)

Y X Y X Y
C c
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 Y x
XH X h
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?

X X H h a) 0/4 (0%)
b) 1/4 (25%)
X H XH XH XH Xh
c) 1/2 (50%)
d) 1/2 (50%)
Y XH Y Xh Y
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?

X X H h a) 0/4 (0%)
b) 1/4 (25%)
X H XH XH XH Xh
c) 1/2 (50%)
d) 1/2 (50%)
Y XH Y Xh Y
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
 Two cell populations
in adult cat:

Active X

Early embryo: Orange

X chromosomes fur
Cell division
Inactive X
and X
chromosome Inactive X
inactivation
Allele for Black
orange fur fur

Allele for Active X

black fur
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 n+1 n–1 n–1 n+1 n–1 n n

Number of chromosomes

Nondisjunction of homologous Nondisjunction of sister

chromosomes in meiosis I 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
A deletion removes a chromosomal
segment.

Duplication
A duplication repeats a segment.

An inversion reverses a segment Inversion

within a chromosome.

A translocation moves a segment

from one chromosome to another,
Reciprocal
nonhomologous one.
translocation
 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
Normal chromosome 9 Reciprocal Translocated chromosome 9
translocation

Philadelphia
chromosome

Normal chromosome 22 Translocated chromosome 22