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10_Human_Genetic_Disease - HumanGeneticDisease...

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H man Genetic Disease Human Genetic Disease Today’s questions: How do patterns of inheritance and natural selection affect human genetic disease? I. Transmission genetics of human disease II Selection dynamics of CF II. III. Selection on late onset illnesses IV G i t i t ti i it d IV. Gene x environment interactions revisited
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I.Transmission genetics of human disease A. Selection against recessive alleles M ( t) i ll l h l f f ti Many (or most) recessive alleles have loss of function or knock out mutations—they do not Why do heterozygotes have a
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II. Selection dynamics of CF alleles Observation 1: CF alleles are at a frequency of about 2% in populations of Northern European ancestry. Given the strength of selection against individuals with the disease phenotype, this is very high–even though Observation 2: Salmonella typhi enters gut cells through the CF gene product. This event starts an infection and may lead to
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Hypothesis: Individuals who are heterozygous for the CF disease allele areprotected against typhoid fever.
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