Conservation of genomic segments (haplotypes): The “HapMap” n In populations, it appears the the linear order of alleles (“haplotype”) is conserved in uninterrupted blocks or “neighborhoods” that tend to be inherited together, with recombination occurring between them n Most populations share common SNP variants within conserved haplotypes n Haplotype blocks and the tag SNPs that identify them will form the HapMap

How could a HapMap be used? n Haplotypes are useful mapping “markers” - they may not contain genes of interest but may be adjacent to genes of interest n What kinds of genes are “of interest”? –Disease susceptibility –Drug metabolism enzymes, leading to sensitivity and/or efficacy

DNA testing 1: Drug sensitivity n Goal of pharmaceutical companies: use of “HapMap” to determine drug use and efficacy in individual patients n Evidence of need: G6PD deficiency and “favism”, response to anti-malarial drugs n “Pharmacogenetics” –Broadly, any genetically determined variation in response to drugs –Narrowly, genetic variations revealed by response to drugs

DNA testing 2: Genetic disease n Prenatal and pre-implantation diagnosis n Individual and population genetic testing –Methods: linkage analysis, mutation analysis (ASOs, DNA chips, direct sequencing) –Criteria: positive result leads to useful action, social and ethical responsibility, high sensitivity and specificity, benefits outweigh costs n Perils of genetic testing