Announcements
1. Dr. Swanson’s powerpoint lecture is now linked to our
lecture schedule. There will be a question on exam 2
from his guest lecture.
2. Reminder: review for exam 2 will be next Wed. 10/16.
Exam 2 will cover material from 9/16 through the end of
this week (10/11).
3. Reminder: homework due and quiz in lab this week - be
prepared for lab.
4. Answers to practice problems posted - skip #19.
Review of Last Lecture
1. Extrachromosomal inheritance: mitochondria and
maternal effect - think about pedigrees
2. Sex determination - different modes
3. Sex determination in humans and the Y chromosome
- how do we know it’s the Y?
- what gene on Y affects maleness and how do we
know?
Outline of Lecture 17
I. Sry and sex determination
II. Dosage compensation
III. Nondisjunction
•
Monosomy
•
Trisomy
IV. Polyploidy
I. SRY codes for Testis-Determining Factor
• Was the object of an intense search.
• SRY gene on the Y chromosome was identified as
the gene that codes for TDF:
– SRY is translocated to X in rare XX males
– SRY is absent from Y in rare XY females
• The “home run” experiment by Koopman et al. used
transgenic mice.
The Transgenic Sry Experiment:
How It Was Done
• Reference: Nature 351:117 (1991)
• Nuclei of fertilized XX eggs were injected with Sry
gene, then the eggs were transplanted to surrogate
mothers.
• Sry gene then randomly incorporated into a
chromosome and was inherited in subsequent cell
divisions.
• Animals karyotyped after development to adult.
Genotypically Female Mice Transgenic for
SRY are Phenotypically Male
XY male
XX male
Genotypically Female Mice Transgenic for
SRY are Phenotypically Male
XY male
XX male
II. Dosage Compensation
• Shouldn’t XX females produce twice the amount of
X-linked gene products (proteins) as XY males?
• No, because XX females “compensate” by
inactivating one of their X chromosomes to make a
single “dosage” of X-linked genes.
Barr Bodies are Inactivated X
Chromosomes in Females
Normal male,
Turner female
0
1
2
3
Normal female,
Klinefelter male
# Barr bodies=
N-1 rule
Inconsistencies between syndromes and
X inactivation
If normal XX female has one X inactivated, why is a X
Turner female not normal?
Similarly, if XXY male has one X inactivated, why does he
have Klinefelter syndrome?
Perhaps not complete inactivation
Or inactivation does not happen immediately,
Then some overexpression of X-linked genes
The Lyon Hypothesis of X Inactivation
• Proposed by Mary Lyon and Liane Russell (1961)
• Which X is inactivated? Inactivation of X
chromosome occurs randomly in somatic cells during
embryogenesis
• Progeny of cells all have same inactivated X
chromosome as original, creating mosaic individual
Lyon-Hypothesis: X-inactivation
A precursor cell to all coat color cells
Random inactivation early in dev.
**Also in calico cats
Mosaicism Reveals the Random
Inactivation of one X chromosome
Anhidrotic ectodermal
dysplasia in a
heterozygous woman
Regions where
sweat glands
are absent.
Sex determination in Drosophila
Female fruit flies are XX; male fruit flies are XY.
Does Y chromosome determine male-ness as it does in humans?
Learning check
Explain how you could determine whether the Y chromosome
determines sex in fruit flies.
Same approach as in human sex determination
humans
flies
XXY: male or female
male
female
XO: male or female
female
male
Ratio of X to autosomes determines sex in flies, as in worms.
1.0 = female
0.5 = male
Dosage compensation in flies
No X- inactivation, but similar gene dosage problem:
females have 2 X chromsomes; males have 1 X.
Solution in flies: X-linked genes in males are transcribed at
twice the level of that in females
A mosaic fruit fly- Bilateral Gyandromorph
(both Male and Female Genotypes)
Occurs from loss of one X (with wildtype alleles) at
1st mitotic division during development, oriented bilaterally.
Male (XO) half:
white,
miniature wing
Female (XX) half:
heterozygous for both
markers
III. Ch. 10 - chromosome “mutations”
Prelude to nondisjunction
Terminology to describe variations in
chromosome number
• Aneuploidy: 2n + or - chromosomes
– Monosomy: 2n - 1
– Trisomy: 2n + 1
• Euploidy: multiples of n
– Diploidy: 2n
– Triploidy: 3n
– Tetraploidy: 4n
Nondisjunction of X chromosome
Nondisjunction also occurs with autosomes
Partial Monosomy:
Cri-du-chat Syndrome (46, -5p)
• Mental retardation, abnormal development of glottis and larynx
• 1 / 50,000 live births
Trisomy:
Down Syndrome (47, +21)
• Characteristic facial patterning, mental retardation
• 1 / 800 live births
Down Syndrome Characteristics
• Most often occurs by nondisjunction of chr. 21 during
meiosis; in theory could occur in either mom or dad, but
95% of these trisomies have defective egg as source
• Prone to respiratory diseases, etc.
• About 30% of all cases of mental retardation in U.S.
• 1/25 can read; 1/50 can write
• Detectable by amniocentesis or chorionic villus sampling
(CVS)
Incidence of Down Syndrome Increases
with Maternal Age
All eggs are
formed by birth
and arrested in
meiosis; is the
correlation of
increased age and
the syndrome
due to more
nondisjunction in
older eggs?
Other trisomies:
Patau Syndrome (47, +13)
• 1 / 19,000 live births
Edwards Syndrome (47, +18)
• 1 / 8000 live births
IV. Polyploidy
Additional sets identical to
parents.
Hybridization of closely
related species; often
sterile.
Generation of Tetraploids Using Colchicine,
a Microtubule Inhibitor
Triploids can be created by inhibition of polar body
formation during oogenesis, followed by fertilization.
Somatic Cell
Hybridization
in Plants creates
Allopolyploid
Hybrids
American Cotton is natural 13 + 13
hybrid