lecture 2

lecture 2 - BICD 100 Genetics Winter 2008 Andrew Chisholm...

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Unformatted text preview: BICD 100 Genetics Winter 2008 Andrew Chisholm Lecture 2 10/1/08 Mendelian Genetics in animals and humans Finish discussion of Mendelian dihybrid crosses Rediscovery of Mendel’s work: Bateson, Cuenot. Chi Squared test. Mendelian genetics in humans Archibald Garrod 1902 studies patients with Alkaptonuria. Analyze family history (pedigree) and find they tend to arise from first-cousin marriages. With Bateson figures out how consanguineous matings lead to homozygosity for recessive trait. Garrod’s 1909 book ‘Inborn Errors of Metabolism’ is first to propose genes affect specific enzymes/proteins, and is comprehensively ignored. Complications of human genetics Matings and environment are not controlled; most families are small, so Mendelian ratios not easy to detect or prove. Use retrospective analysis of pedigree to form hypothesis about how disease (or other trait) is inherited. Know the most important pedigree symbols. Use probability rules to calculate chances of particular allele combinations. Calculate probability of homozygosity by descent. Probability of multiple events. Modes of inheritance 1. Autosomal recessive Appear in multiple offspring of unaffected parents. Parents consanguineous (first cousins or small isolated population). Alkaptonuria (black urine), not to be confused with Phenylketonuria (PKU; musty smelling urine and mental retardation) 2. Autosomal dominant e.g. Huntingdon’s disease; hypercholesteremia (LDL receptor deficiency) ‘Vertical’ inheritance. Both sexes affected. Affected transmit to ~50% offspring. 3. X-linked recessive Only (or predominantly) males affected, females are carriers and transmit to ~50% offspring. No father-son transmission. Transmission of hemophilia in descendants of Queen Victoria and the downfall of the Tsars of Russia. 4. X-linked dominant (very rare). Will resemble autosomal dominant except that cannot be transmitted father-son 5. Y-linked (theoretically possible but unclear if ever observed). Exclusive male-male transmission of Y allows male line paternity testing. Autosomes versus sex chromosomes. More complicating factors Many diseases exhibit partial penetrance (not all individuals of same genotype are affected) and incomplete expressivity (severity of disease can vary). Some but not all of this may be due to other interacting genes (multiple loci) or environment. Reading for Lecture 2 Probability: Chapter 3 pp 53-58. Human genetics: Chapter 6 pages 132-140. Integrative case study of PKU Part I on p 156 BICD 100 Genetics Winter 2008 Andrew Chisholm References for Lecture 2 These are not required reading but are provided for anyone interested in ‘the real data’. All the citations are online: use PubMed for recent literature, JSTOR or ESP for older papers. PubMed: http://www.ncbi.nlm.nih.gov/sites/entrez/ JSTOR http://www.jstor.org/ Classic genetics papers: http://www.esp.org/ Garrod, Archibald E. 1902. The Incidence of Alkaptonuria: A Study in Chemical Individuality. Lancet, vol. ii, pp. 1616-1620. Y chromosomes, Thomas Jefferson and Sally Hemings Foster, E.A. et al. 1998. Jefferson fathered slave’s last child. Nature 396: 27-28. See also the Nature letters section on 7 January 1999, where Foster et al admit the title to their letter was “misleading”. Marshall, E. 1999. Which Jefferson was the father? Science 283: 153-155. The controversy goes on and on, at least among Jefferson historians: http://www.monticello.org/plantation/hemingscontro/hemings_resource.html ...
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