5Dominantly Inherited Disorders - Huntington’s Disease The DiseaseDegenerative disease of the nervous system - progressive neural cell death caused by build up of the protein huntingtin (mutated form).No cure. Terminal years post-diagnosis.CauseAssociated with a triplet (CAG) repeat in the gene for huntingtin.GeneticsLethal in heterozygotes.50% chance of passing the disease to progeny.
6Huntington’s Disease (Cntd.) Why does the allele persist?Late onset of disease - symptoms at 35 to 40 years old.
9Chromosomal Theory of Inheritance Walter Sutton, 1902Pre-SuttonChromosomes, centrioles, and mitochondria all divide and segregate in meiosis.Which of these structures are responsible for heredity (follow Mendel’s rules)?Sutton’s Evidence (Sutton, )1. Gametes(a) Must have equal hereditary contributions - sperm contain little cytoplasm, but do have nuclei. Hereditary material probably in the nucleus.(b) Somatic cells have 2 homologous chromosomes, but gametes have only 1. Consistent with Mendel’s model.
10Chromosomal Theory of Inheritance (Cntd.) Sutton’s evidence (Cntd.)2. Mendel’s LawsChromosomes segregate and assort independently in meiosis.Response of the Scientific CommunityThere are more genes than chromosomes!The Final EvidenceThomas Hunt Morgan, eye color in Drosophila.Read P
12Morgan’s Experiment - Sex Linkage (Cntd) Crossed the F1 females with the male parent.What ratio would you predict?Obtained a 1:1:1:1Segregation of white eyed trait had a 1:1 correspondence with segregation of the X chromosome Mendel’s observation of segregation of alternate traits reflected chromosome behavior.
13Autosomes and Sex Chromosomes Principle function - sex determination.Which sex determines progeny sex (human)?Features of the Y Chromosome (human)Carries 78 active genes, including a sex-determining gene (SRY).Sex Linked GenesAny gene (does not have to be involved with sex) that is carried on the sex chromosomes (usually on X).
15Barr Body1 X chromosome in each female somatic cell is inactivated early in development female cells produce the same amount of protein from the X as do male cells.
16Nondisjunction Nondisjunction of Autosomes The failure of homologues or sister chromatids to separate in meiosis aneuploidy.Nondisjunction of AutosomesEffects are either fatal or severe.Down Syndrome (Trisomy 21)
17Nondisjunction (Cntd.) Nondisjunction of Sex ChromosomesGenerally, the effects are not as severe as nondisjunction of autosomes.1. X Chromosome(a) Triple X SyndromeUsually taller than average females, generally “normal” and most are *fertile.(b) Klinefelter SyndromeXX + Y XXYSterile male with female characteristics and sometimes mildly impaired intelligence.
18Klinefelter SyndromeKlinefelter calico cat - evidence that Y chromosome determines maleness.
19Nondisjunction of Sex Chromosomes (Cntd.) (c) Turner Syndrome (Monosomy X)X + O XOShort females with edema (resulting in webbed neck) that are almost always sterile.
20Nondisjunction of Sex Chromosomes (Cntd.) (d) OYO (egg) + Y OYLethal - genes on the X chromosome are necessary for survival.2. Y ChromosomeX + YY (sperm) XYYTall, fertile males.Genetic CounselingRead P 274.