Download Lecture 14 - The Chromosomal Basis of Inheritance

Lecture 14 – The
Chromosomal Basis of
Inheritance
In this lecture…
• Linking Meiosis and Punnet Squares
– Sex-linked traits
• X inactivation
• Linkage
• Altering chromosome structure
– Polyploidy and aneuploidy
• Epigenetics
Linking Meiosis and Punnet
Squares
How did we first figure out
where genes were on chromosomes?
• The first solid evidence associating a specific
gene with a specific chromosome came from
Thomas Hunt Morgan, an embryologist
• Morgan’s experiments with fruit flies provided
convincing evidence that chromosomes are
the location of Mendel’s heritable factors
• Fruit flies are great model organisms
– Only four pairs of chromosomes
Morgan’s Contributions
• Confirmed the chromosomal theory of
inheritance: genes are located on
chromosomes
• Discovered gene linkage
Wild type
• Morgan noticed certain traits were much
more common in flies
• These traits he called wild type (as in much
more likely to be found in the wild)
Wild-type
Mutant
Morgan’s experiments
• 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-eyed
mutant allele must be located on the X
chromosome
EXPERIMENT
Figure 15.4
P
Generation
F1
Generation
All offspring
had red eyes.
RESULTS
F2
Generation
CONCLUSION
P
Generation
X
X
w
X
Y
w
w
Eggs
F1
Generation
Sperm
w
w
w
w
w
Eggs
F2
Generation
w
w
Sperm
w
w
w
w
w
w
w
Sex-linked traits
• Only males had the white eyes
• Why did the males get the short end of the
stick?
• Color-blindness is a sex-linked trait
– Genes for sex-linked traits are carried on the sex
chromosomes
– More specifically, it is an X-linked trait
Sex-linked traits
• There are about 1,000 sex-linked genes
– These genes are found only on the sex chromosomes
• These genes are on the X chromosome, but not on the Y
– A female with XX will have two copies of an X-linked gene
– A male with XY will have one copy of an X-linked gene
Male
Female
Male
Why are men more susceptible to
some genetic diseases?
• If the male receives a defective
copy of a sex-linked gene/alelle,
he has no functional copy as a
backup
• Therefore, he has whatever
disease is associated with that
defective allele
Sex Chromosomes
• X chromosome have genes for many
characters unrelated to sex, whereas the Y
chromosome mainly encodes genes related to
sex determination
• Female is the default sex?
More about the sex chromosomes
• Autosomes vs. sex chromosomes
• Only the ends of the Y chromosome have regions
that are homologous with corresponding regions
of the X chromosome
• Each ovum contains an X chromosome, while a
sperm may contain either an X or a Y
chromosome
• The SRY gene on the Y chromosome codes for a
protein that directs the development of male
anatomical features
– The SRY gene is pleiotropic
Sex determination in other animals
• X and Y are not the
only way to
determine sex
Punnet Squares and X-linked
genes
• For a recessive X-linked trait to be expressed
– A female needs two copies of the allele
(homozygous)
– A male needs only one copy of the allele
(hemizygous)
Figure 15.7
Transmission of X-linked recessive traits
XNXN
Sperm
Eggs
(a)
Xn
XNXn
XnY
Sperm XN
Y
XN
XNXn XNY
XN
XNXn XNY
Eggs
(b)
XNY
XNXn
Sperm
Y
XN
XNXN XNY
Eggs XN
Xn
XNXn XnY
Xn
(c)
Xn
XnY
Y
XNXn XNY
XnXn
XnY
Punnet Squares and X-linked
genes
• A couple goes to a genetic counselor, wondering
about the possibility of their children inheriting Xlinked colorblindness. The man is colorblind, but the
woman is not, and does not have a history of it in her
family. What is the probability that:
– Their first child will be female
– Their sixth child will be female
– Their female children will be colorblind
– Their male children will be colorblind
Genetic disorders caused by
defective X-linked genes
• Some disorders caused by recessive alleles on
the X chromosome in humans
– Color blindness (mostly X-linked)
– Duchenne muscular dystrophy
– Hemophilia
• 30% of cases are spontaneous
Hemophilia and the Queen
• Britain’s Queen Victoria was a carrier for hemophilia
• She passed the allele to royal households across
Spain, Germany and Russia
• Called “the royal disease”
Aneuploidy in the sex
chromosomes
• Aneuploidy: having an unusual number of
chromosomes
• Sometimes, you can get aneuploidy involving extra
sex chromosomes
– XXY, XXX, XYY
• However, someone with an XY genotype can have a
female phenotype if the SRY gene is damaged
• Similarly, someone with XX genotype can be
phenotypically male if the SRY gene is translocated
onto the X
– In 1996, a test based on a molecular probe for SRY was
used to ensure that potential competitors for the
women's Olympic events in Atlanta had no SRY gene
X aneuploidies
• Monosomy X, called Turner syndrome, is the
absence of an X in females (XO)
–
–
–
–
The only known viable monosomy in humans
Incomplete development at puberty
Short height
Infertility
• Kleinfelter Syndrome is the presence of an extra
X in males (XXY)
– Gynecomastia
– Abnormal body proportions
– Infertility
• Male XYY Syndrome
X inactivation in female mammals
• One of the two X chromosomes in each cell is
randomly inactivated during embryonic
development
• The inactive X condenses into a Barr body
• If a female is heterozygous for a particular gene
located on the X chromosome, she will be a mosaic
for that character
Barr Bodies in Calico Cats
Are there male
calico cats?
Linked Genes
• Linked genes are genes that tend to be
inherited together
– They are located very close to each other on a
chromosome
– They are unlikely to be separated during
homologous recombination and independent
assortment
Homologous recombination during meiosis “can cause alleles previously on
the same chromosome to be separated and end up in different daughter
cells. The farther the two alleles are apart, the greater the chance that a
recombination event may occur between them, and the greater the chance
that the alleles are separated.”
Linkage maps
• The first chromosome maps were linkage
maps
• A linkage map shows the positions of known
genes relative to each other in terms of
recombination frequency
– The greater the frequency of recombination
between two genes, the farther apart they are
• Genes that are far apart on the same
chromosome can have a recombination
frequency near 50%
Calculating recombination frequencies
• Recombination frequency is the frequency with
which a single chromosomal crossover will take
place between two genes during meiosis
A miniature linkage map
A cow linkage map
Uses of linkage maps
• 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 won’t tell you exactly where a
gene is located on a chromosome
Damaging chromosomes
• Damaging or altering chromosome structure
can lead to genetic disorders
– Removing or adding a chromosome
– Deleting part of a chromosome
– Translocating part of a chromosome
• Alteration of chromosome structure is the
main culprit behind spontaneous abortions in
humans
• Plants can withstand largescale chromosome
alteration better than animals
Aneuploidy (again)
• Aneuploidy is a result of nondisjunction
– Chromosomes fail to separate during meiosis
• As a result, one gamete receives two of the
same type of chromosome, and another
gamete receives no copy
Aneuploidy in humans
• Aneuploidy occurs in 1 in 160 live births
• Most aneuploidies result in spontaneous
abortion
• Most common error is trisomy 16 – not
possible to survive
• Risk of aneuploidy increases with the age of
the mother
Aneuploidy in humans
• Trisomy 21
– Down syndrome
– Small chin, round face, almond-shaped
eyes, shorter limbs, high risk for
heart defects
• Trisomy 18
– Edwards syndrome
– Small head, small jaw, cleft palate, clenched hands, heart
defects
• Trisomy 13
– Patau syndrome
– Heart defects, kidney defects mental
retardation, polydactylyl, cyclopia,
abnormal cranial development
Polyploidy vs. Aneuploidy
• Polyploidy is a condition in which an organism has
more than two complete sets of chromosomes
– Triploidy (3n) is three sets of chromosomes
– Tetraploidy (4n) is four sets of chromosomes
• Polyploids are
more normal in
appearance than
aneuploids
• ‘Odd’ polyploids
are usually sterile
Polyploidy in plants
• Polyploidy is common in ferns and flowering
plants
– 30-70% of plants are polyploid
• Polyploidy gives an opportunity for greater
heterozygosity
– Instead of two alleles with diploids, polyploids can
have n number of alleles
– Some polyploid plants have
larger fruit
Seedless fruit
• Some varieties of seedless fruit are triploid
• Odd-numbered polyploids are usually sterile,
and produce no seeds
Triploid
Tetraploid
Hexaploid
Octaploid
Apple, banana,
oranges,
watermelon
Apple, cotton,
potato, cabbage,
peanut
Wheat, oats,
kiwi,
chrysanthemum
Strawberry,
sugarcane
Seedless…animals?
Polyploidy in yeast
• Some years ago, yeast underwent genome
duplication
• They received an extra copy of their genome
and became polyploid
• The extra genome had no evolutionary
selective pressure on it, and could evolve in
any random direction
• Yeast evolved alcohol fermentation in that
extra genome copy
Alteration 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 orientation of a segment
within a chromosome
– Translocation moves a segment from one
chromosome to another
Diseases due to chromosome
alterations
• The 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
Figure 15.16
Normal chromosome 9
Normal chromosome 22
Reciprocal translocation
Translocated chromosome 9
Translocated chromosome 22
(Philadelphia chromosome)
Genomic Imprinting
• For a few mammalian traits, the phenotype
depends on which parent passed along the
alleles for those traits
• Such variation in phenotype is called genomic
imprinting
• Genomic imprinting involves the silencing of
certain genes that are “stamped” with an
imprint during gamete production
Hold on…
• Genomic imprinting is a bit of an archaic term
• Most genes have some sort of imprinting
• Today, genomic imprinting is called
epigenetics
How epigenetics works
• One of the main determinants of whether a
gene is expressed is where it is physically
located in the genome
– Euchromatin is DNA bound loosely with protein,
and is often expressed
– Heterochromatin is DNA bound up tightly with
protein, and is rarely expressed
• Parental experiences can compress or unwind
DNA
How epigenetics works
• What determines how the tightly the DNA is wound?
– Methylation (addition of –CH3 to nucleotides)
produces euchromatin
• Studying methylation patterns it the basis of a new field
of biology called epigenomics
Angelman’s syndrome and PraderWilli Syndrome
• Caused by improper epigenetic regulation on chromosome 15
• Normally, one chromosome is expressed while the
homologous chromosome is silenced through demethylation
• In Angelman’s syndrome, the maternal copy is lost through
chromosomal deletion while the paternal copy is silenced
– Symptoms: developmental delay, speech impediment, seizures, very
happy personality
• In Prader-Willi syndrome, the paternal copy is lost through
chromosomal deletion while the maternal
copy is silenced
– Symptoms: developmental delay, short
stature, weak muscles, excessive and
unsatisfied hunger
Inheritance of cell
organelles
• Mitochondria, chloroplasts, and plastids are
inherited from the mother
– The sperm is not big enough to hold all the organelles
• You can trace your maternal line through your
mitochondrial genome
• Some defects in mitochondrial genes prevent
cells from making enough ATP and result in
diseases that affect the muscular and nervous
systems
Vocabulary
•
•
•
•
•
•
•
Wild-type
SRY gene
Hemophilia
Sex-linked trait
Barr body
Linkage maps
Aneuploidy
– Down syndrome,
Edwards syndrome,
Patau syndrome
– Turner syndrome,
Kleinfelter syndrome
• Polyploidy
– In yeast and plants
• Chromosomal alterations
– Deletion, duplication,
inversion, translocation
•
•
•
•
Methylation
Euchromatin
Heterochromatin
Epigenetics
– Angelman’s syndrome
and Prader-Willi
syndrome