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Complex traits: intersection of genes and environment

Complex traits: intersection of genes and environment. “Discontinuous” (single-gene) traits vs. “continuous” (multi-genic) traits how much is due to genetic component and how much to environment? - heritability Many, perhaps most, human clinical traits of importance are complex

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Complex traits: intersection of genes and environment

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  1. Complex traits: intersection of genes and environment • “Discontinuous” (single-gene) traits vs. “continuous” (multi-genic) traits • how much is due to genetic component and how much to environment? - heritability • Many, perhaps most, human clinical traits of importance are complex • but most understanding is coming from mouse genetics

  2. Examples of human complex traits • Coronary artery disease (CAD) • a very low frequency of this can be simply explained by familial hypercholesterolemia (LDL receptor mutations) • most is multigenic with variable susceptibility • Cancers, e.g., BRCA1/BRCA2

  3. The mouse as a model for study of obesity • Cloning of the mouse ob and db genes • role of parabiosis experiments to identify circulating and non-circulating factors • ob encodes leptin • Db encodes the leptin receptor • Other influencing mouse genes, including those encoding a leptin transporter, neuropeptide Y and melanocortin 4, reveal complexity

  4. The mouse as a model for study of cancer • Murine multiple intestinal neoplasia (Min) • ENU-induced mutation in APC (important in human colon cancer) • major modifier mapped to chr. 4 - Mom (modifier of Min), encoding a secrretory phospholipase A2

  5. The mouse as a model for study of cancer - mapping modifier QTLs • The system: transgene-induced mammary tumor model • The observation: background-dependent latency, tumor growth and metastatic progression • The resource: backcross mapping panel • The result: identification of QTLs controlling latency, metastasis, etc.

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