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A second practice problem set (with answers) is on the course website.

A second practice problem set (with answers) is on the course website. The review session for the second midterm is on Thursday evening, April 10, from 7-9pm in ROOM 141 GIANNINI HALL. determines . G enotype of mother. progeny phenotype mutant.

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A second practice problem set (with answers) is on the course website.

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  1. A second practice problem set (with answers) is on the course website. The review session for the second midterm is on Thursday evening, April 10, from 7-9pm in ROOM 141 GIANNINI HALL

  2. determines Genotype of mother progeny phenotype mutant determines (or at least influences) the m/m vs. m/+ progeny: m/m, m/+, or +/+ mother: Phenotype of the progeny progeny phenotype wildtype progeny: m/m, m/+, or +/+ Strict maternal effect (only mother can supply the needed + gene product) (for a blowfly) mentioned GSD via a Maternal Effect system

  3. influences Genotype of mother progeny phenotype mutant determines (or at least influences) the m/m vs. m/+ m/m vs. m/+ progeny: m/m, m/+, or +/+ mother: mother: Phenotype of the progeny progeny phenotype wildtype progeny phenotype wildtype progeny: m/m, m/+, or +/+ Strict maternal effect (only mother can supply the needed + gene product) progeny phenotypemutant m/m or m/+, or +/+ progeny: progeny phenotypewildtype progeny: m/m, m/+, or +/+ Rescuable maternal effect (either mother or progeny can supply + gene product) (for a blowfly) mentioned GSD via a Maternal Effect system

  4. X chromosome 2800 genes X-chromosome dosage compensation in Drosophila: Are male X-linked genes turned UP or are female X-linked genes turned DOWN? Giant Polytene Salivary-Gland Chromosomes measure rate of RNA precursor incorporation into “nascent” transcripts (during interphase) …average transcription rates (per unit DNA)

  5. average transcription rates (per unit DNA): female X = femaleautosomes = maleautosomes< male X X chromosome 2800 genes transcription rate for Male X-linked genes are turned UP relative to autosomal or female X-linked genes

  6. Female: XX Male: XY noX hyperactivation X hyperactivation Phenotypic consequences of loss by mutation: Normal gene function: What phenotype would one expect for mutations that disrupted genes that encode the machinery for X-chromosome dosage compensation? needed (only) for hyper male (X:A=0.5)-specific lethal needed (only) to preventhyper female (X:A=1)-specific lethal That is how the relevant genes are recognized (MSLs encode protein complex on male X)

  7. Fig. 18.23 (p675) Sxlnullis female-specific lethal SxlConstitutiveis male-specific lethal also dosage compensation Among the genetic pathways that control development, those controlling sexual development are perhaps the best understood. Sxl controls sex determination; dsx controls sexual dimorphism

  8. XX AA X AA hermaphrodites (females that make sperm) males What about worms? (C. elegans) (1) both hermaphrodite X’s active (like the fly) (2) male X twice as active as each hermaph. X (like the fly) (3) at the transcriptional level (like the fly) (4) hermaph.-specific lethal genes encode protein complex on hermaphrodite X’s that turns transcription down fly male-specific lethal genes encode protein complex on male X that turns it up

  9. XY AA XX AA First clue: “sex chromatin” females males Barr Body rule: One Barr Body No Barr Body #BB = #X-1 XO AA Turner females XXY AA Kleinfelter males XXXX AA (mentally retarded) females How do we mammals dosage compensate? NoBarr Body OneBarr Body ThreeBarr Bodies

  10. G6PD+/G6PD-: heterozygote Another clue: Odd behavior of an X-linked mammalian gene: Individual blood cells are phenotypically either G6PD+or G6PD- only one or the other X-linked allele seems to be active in any given blood cell not what we saw with the eye of the w+/w-fly

  11. XY AA Xx AA females males mosaic c+ expression whenc+ on X (translocation of autosomal coat color gene c to X) (1) Barr Body = inactivated X chromosome Xxxx AA x females Barr Body Geneticist Mary Lyon: #BarrBodies= #X-1 mosaic expression of G6PD+(on X) Observations: Hypothesis: (2) Dosage compensation by inactivation of all but one X chromosome

  12. X-chromosome inactivation: XmaternalXpaternal (1) initiated very early in development (at ~500 cell stage in humans) (2) generally random in embryo proper (paternal = maternal) (often paternal in extra-embryonic) (3) once initiated, stably inherited an epigenetic phenominon (4) reactivation of inactivated X occurs in germ cells during oogenesis

  13. hemizygous males (EDA-/Y) & homozygous females (EDA-/EDA-) no sweat glands (incl. breasts) missing & abnormal teeth/hair EDA+/EDA- PHENOTYPIC MOSAICS Identical twins: Patchiness signifies little skin cell mixing during development Striking human example of X inactivation in action: Anhidrotic Ectodermal Dysplasia (EDA): cell autonomous trait

  14. Need to know for gene a: how is a phenotype related to a+ gene expression? (2) perhaps cell autonomous, but deleterious early --- abnormal cells selected against (they may be outcompeted by normal cells) For X-linked genes: If a+/a-mammals are functional mosaics of a+ & a- cells …are all non-functional X-linked alleles (a-) semi-dominant? (dominance depends on how phenotype is operationally defined) NO (1) perhaps not cell autonomous (and 50% a+ function is sufficient for normal phenotype) consider hemophilias Most animals compensate well for cells lost during development

  15. X1matX1pat 50:50mat vs. pat active the genetics of the X controlling element X2matX2pat50:50 mat vs. pat active 65:35mat(1) vs. pat(2) active X1matX2pat X2matX1pat 35:65mat(2) vs. pat(1) active Mapping the source of the inactivation bias definedXce

  16. c+ almost all genes in cis shut off X Study of variations in “X inactivation strength” (in whole mice) defined the Xce (controlling element) (determines chromosomal inactivation competativeness) Study of T(X,A)s in mouse tissue-culture cells defined the Xic (inactivation center) (“source” of inactivation in cis) Xic = Xce

  17. (s) (number of) Xist X-inactivation-specific-transcript: X X X X X X Xic = Xce The source of a very odd RNA : …a non-coding RNA from the inactive X that coats the inactive X chromosome in cis one of the first examples of a regulatory RNA

  18. X X Xist RNA X Xist RNA X Consequences of deleting Xic (source of Xist): always the active X

  19. Xist transgene (inducible) on autosome will coat autsome with Xist and silence it …but only during an early window of time

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