Download Ch 15: Sex Determination & Sex Linkage

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
seeds (YYRR)
Green-wrinkled
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)
F2
Generation
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
Black body,
vestigial wings
(double mutant)
Gray body,
normal wings
(F1 dihybrid)
Replication of
chromosomes
Replication of
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
with the new allele
combinations.
Recombinant
chromosomes
Sperm
Ova
Gametes
Ova
Testcross
offspring
Sperm
965
Wild type
(gray-normal)
944
Blackvestigial
Parental-type offspring
206
Grayvestigial
185
Blacknormal
Recombinant offspring
Recombination
391 recombinants
=
 100 = 17%
frequency
2,300 total 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
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
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
Chromosome
cn
vg
I
II
Y
X
IV
III
Mutant phenotypes
Short
aristae
0
Long aristae
(appendages
on head)
48.5
Gray
body
Vestigial
wings
Cinnabar
eyes
Black
body
57.5
67.0
Red
eyes
Wild-type phenotypes
Brown
eyes
104.5
Normal
wings
Red
eyes
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)
XC Xc
● 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 Xc
a) 1/4 (25%)
c
X
XC Xc Xc Xc
b) 1/4 (25%)
Y
XC Y
d) 1/2 (50%)
Xc Y
c) 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…
H
X Y
x
H
X
h
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
Y
Xh
XH XH XH Xh
XH Y Xh Y
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
Two cell populations
in adult cat:
Active X
Early embryo:
Orange
fur
X chromosomes
Cell division
Inactive X
and X
chromosome Inactive X
inactivation
Black
fur
Allele for
orange fur
Allele for
black fur
Active X
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
Number of chromosomes
Nondisjunction of homologous
chromosomes in meiosis I
Nondisjunction of sister
chromatids in meiosis I
n
● 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
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.
Deletion
Duplication
Inversion
Reciprocal
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
translocation
Translocated chromosome 9
Philadelphia
chromosome
Normal chromosome 22
Translocated chromosome 22