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 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?

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 female, Klinefelter male Normal male, Turner female 1 2 3 # 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. Female (XX) half: heterozygous for both markers Male (XO) half: white, miniature wing

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

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