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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.
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
0 1
2 3
Normal male,Turner female
Normal female,Klinefelter male
# Barr bodies=N-1 rule
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?
Inconsistencies between syndromes and X inactivation
Perhaps not complete inactivationOr inactivation does not happen immediately,Then some overexpression of X-linked genes
• 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
The Lyon Hypothesis of X Inactivation
Random inactivation early in dev.
A precursor cell to all coat color cells
Lyon-Hypothesis: X-inactivation
**Also in calico cats
Mosaicism Reveals the Random Inactivation of one X chromosome
Regions wheresweat glandsare absent.
Anhidrotic ectodermal dysplasia in a heterozygous woman
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 chromosomedetermines sex in fruit flies.
humans flies
XXY: male or female male female
XO: male or female female male
Same approach as in human sex determination
Ratio of X to autosomes determines sex in flies, as in worms.
1.0 = female0.5 = 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)
Male (XO) half:white,miniature wing
Female (XX) half:heterozygous for bothmarkers
Occurs from loss of one X (with wildtype alleles) at1st mitotic division during development, oriented bilaterally.
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
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 syndromedue to more nondisjunction in older eggs?
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 bodyformation during oogenesis, followed by fertilization.