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.

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

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

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 syndromedue to more nondisjunction in older eggs?

Patau Syndrome (47, +13)

• 1 / 19,000 live births

Other trisomies:

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 bodyformation during oogenesis, followed by fertilization.

Somatic Cell Hybridization

in Plants createsAllopolyploid

Hybrids

American Cotton is natural 13 + 13 hybrid