Announcements

1. 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.

2. Review of Last Lecture Extrachromosomal inheritance: mitochondria and maternal effect - think about pedigrees Sex determination - different modes 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?

3. Outline of Lecture 17 • I. Sry and sex determination • II. Dosage compensation • III. Nondisjunction • Monosomy • Trisomy • IV. Polyploidy

4. 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.

5. 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.

6. Genotypically Female Mice Transgenic for SRY are Phenotypically Male XY male XX male

7. Genotypically Female Mice Transgenic for SRY are Phenotypically Male XY male XX male

8. 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.

9. Barr Bodies are Inactivated X Chromosomes in Females Normal female, Klinefelter male Normal male, Turner female 0 1 2 3 # Barr bodies= N-1 rule

10. 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

11. 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

12. Lyon-Hypothesis: X-inactivation A precursor cell to all coat color cells Random inactivation early in dev. **Also in calico cats

13. Mosaicism Reveals the Random Inactivation of one X chromosome Anhidrotic ectodermal dysplasia in a heterozygous woman Regions where sweat glands are absent.

14. 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.

15. Same approach as in human sex determination humansflies 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

16. 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

17. 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. Female (XX) half: heterozygous for both markers Male (XO) half: white, miniature wing

18. III. Ch. 10 - chromosome “mutations” Prelude to nondisjunctionTerminology 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

19. Nondisjunction of X chromosome Nondisjunction also occurs with autosomes

20. Partial Monosomy:Cri-du-chat Syndrome (46, -5p) • Mental retardation, abnormal development of glottis and larynx • 1 / 50,000 live births

21. Trisomy:Down Syndrome (47, +21) • Characteristic facial patterning, mental retardation • 1 / 800 live births

22. 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)

23. 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?

24. Other trisomies: Patau Syndrome (47, +13) • 1 / 19,000 live births

25. Edwards Syndrome (47, +18) • 1 / 8000 live births

26. IV. Polyploidy Hybridization of closely related species; often sterile. Additional sets identical to parents.

27. Generation of Tetraploids Using Colchicine, a Microtubule Inhibitor Triploids can be created by inhibition of polar body formation during oogenesis, followed by fertilization.

28. Somatic Cell Hybridizationin Plants createsAllopolyploidHybridsAmerican Cotton is natural 13 + 13 hybrid