lec10 - BE.104 Spring Environetics; Cause and Effect J. L....

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BE.104 Spring Environetics; Cause and Effect J. L. Sherley Outline I. Environetics II. Cause-Effect Determination I. ENVIRONETICS Definition: Environetics is that discipline that seeks to detect and quantify cause-effect relationships between non- infectious environmental agents and human health. Environetics employs concepts from epidemiology, biostatistics, logic, and good ol’ common sense to make this determination. For perspective, consider "The Genetic Paradigm of Disease" 1 Figure 1A:
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"All diseases are genetic." Not necessarily "hereditary," but caused by defects in genes. Refinement: All diseases are genetic except for those caused by toxins and infectious agents, which may also have dependencies on genotype (e.g., susceptibility) Genetics- Currently this discipline is out of control vs. environmental mechanisms Are all diseases due to defects in genes? 3 Figure 5A:
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Genetic Pedigree Analysis The gold standard for analysis of genetic disease factors Discover genetic disease causation (i.e. gene) by: 1) Relating disease patterns to genetic rules Genotype classification a) dominant b) recessive c) x-linked d) age-dependent (e.g. childhood cancers) 2) “Quantitative relating” is called linking , a statistical method for detecting and quantifying the significance of associations between genotype and disease occurrence (e.g., genotyping across 3x10 9 bp!; mutation analyses; LOD score) 3) Establishing cause-effect: strength of association prospective analysis (genotype before disease) animal models (some limitations) 5
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Genetics Features Rules 1) gene product (protein, ribonucleic acid) function for health 2) Mendelian segregation- 1884 Confounders of the Analysis 1) Penetrance (“mutation expressivity”) 2) Imprinting- specific subset of penetrance (mechanism known) 3) Phenocopy - (phenotype for other reasons besides the gene of origin) 4) Ascertainment (e.g., determining familial relationship) 5) “Environment effects” 6) Statistical variation? Yes, spontaneous mutations (sporadic cases) Statistics requirements- n is small Key Research Tool - Old - Linkage analysis (stat. associations) New - Genomics: How genes are expressed “quantitative gene expression pedigrees” may be next Experimental Support - Mouse models-Disease synteny T r a n s g e
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Environetics 7
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persons, exposures, geographical space, time The component that genetics leave out The Environmental Health Science Study
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This note was uploaded on 11/11/2011 for the course BIO 20.010j taught by Professor Lindagriffith during the Spring '06 term at MIT.

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lec10 - BE.104 Spring Environetics; Cause and Effect J. L....

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