1 / 19

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.

arianna
Télécharger la présentation

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

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related