Announcements 1. We have decided to halt our efforts with the yw crosses, due to uncooperative yw females, frustration, and lack of motivation (we KNOW the expected results). There will be no assignment due for this lab activity. You are responsible for understanding the expected results and how to calculate recombination frequencies and map distance (ie. flylab 6). 2. You should continue your X-linked crosses. 3. Vote on when to review for exam 2 (10/17, 10/18) - Mon. evening or in class Wednesday. If we review in class Wed, then class meets Fri. If we
review Mon., then class meets Wed. 4. Is there a serious problem taking the exam on Thurs. or Fri.??? 5. Reminder that homework is due next Tues., Wed. 6. Quiz in lab next week; be prepared - pick up lab7 overview and read it. 7. Practice problems for Ch.8: 1,3,9,11; Ch.9: 4,8,10 Review of Last Lecture 1.Quick review of conjugation: F-, F+, Hfr 2. Transformation: a different process of recombination,
can be used to map genes 3. Bacteriophages are viruses that use bacteria as hosts; they can mediate bacterial DNA transfer - transduction 4. Extrachromosomal inheritance: Phenotype of maternal parent is solely responsible for phenotype of offspring example of maternal inheritance of chloroplasts Outline of Lecture 16 I. Two more examples of extrachromosomal inheritance: mitochondria and maternal effect
II. Modes of sex determination III. Humans and sex determination IV. Dosage compensation I. Mitochondrial Heredity About 30,000 genes on 23 human chromosomes (3.3 billion base pairs/haploid cell) Mitochondrial Genome contains 37 genes: 13 code for some of the proteins involved in
oxidative respiration 22 tRNA genes 2 rRNA genes some proteins involved in mt protein synthesis 16,569 base pairs, circular Human Mitochondrial Diseases Are maternally inherited: only offspring of affected mothers are affected
Show deficiency in mitochondrial function Are caused by a mutation in a mitochondrial gene Example: myoclonic epilepsy and ragged red fiber disease (MERRF) Deafness, dementia, seizures Point Mutation in a mitochondrial tRNA Other Human Mitochondrial Diseases
Lebers Hereditary Optic Neuropathy (LHON) Sudden bilateral blindness Point mutation in small subunit of NADH dehydrogenase Kearns-Sayre Syndrome (KSS) Symptoms in eyes, muscles, heart, brain Deletion mutation in mtDNA Maternal Effect: Snail Coiling
Pattern of offspring determined by genotype of mother, regardless of phenotype dextral DD dd D egg, d sperm
dextral Dd sinistral D sperm, d egg Dd
sinistral Maternal Effect Genes in Drosophila Development Discovered by Edward Lewis, Christiane NussleinVolhard and Eric Weischaus (Nobel Prize in Physiology or Medicine, 1995) Gene products deposited in egg by cells of mothers ovary.
These genes set up the first embryonic axes: dorsalventral and anterior-posterior and control later zygotic genes. II. Sex Determination Gene Map of the Y Chromosome
Modes of Sex Determination XX/XO (Protenor) absence of second X chromosome determines maleness as in Caenorhabditis elegans XX/XY (Lygaeus) presence of Y chromosome determines maleness in mammals sometimes females are heterogametic sex
Female Male XX/XO (Protenor) Mode 1:1 SEX RATIO
C. elegans Sex Determination XX X/Autosome Sets = 1 XO X/Autosome
Sets = 0.5 III. Normal Human Karyotypes Female Male Klinefelter Syndrome (47, XXY)
Some male dev. but no sperm, and some female dev. too. 2 in 1000 male births Turner Syndrome (45, X)
Female dev. but no eggs. 1 in 3000 female births The Odyssey of the Germ Cells Primordial Germ Cells are set aside early in embryonic development PMGs migrate to embryonic kidney ridges:
If cells are XY, medulla develops into testes under direction of male hormones around week 7 If cells lack a Y, cortex develops into ovary, also under active hormonal control Active gene expression required in either case Duct differentiation: If XY, Wolffian ducts > epididymis and vas deferens If no Y, Mullerian ducts > oviduct
The Human Y Chromosome NRY is non-recombining region of Y 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 IV. Dosage Compensation Shouldnt XX females produce twice the amount of Xlinked gene products 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 The Lyon Hypothesis of X Inactivation Proposed by Mary Lyon and Liane Russell (1961) 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 Mosaicism Reveals the Random Inactivation of one X chromosome Regions where
sweat glands are absent. 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
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