EHJ352H1 Lecture Notes - Lecture 11: Whole Genome Sequencing, Exome Sequencing, Copy-Number Variation

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Massive amounts of genomic diversity in humans. Purifying selection will lead to low divergence as well as low rate of mutation and short coalescence time. High rate of positive selection would increase diversity. Most changes have no effect on fitness and increase diversity. Most changes strongly deleterious cause decreased diversity. High mutation rate, increased diversity; low mutation rate, decreased diversity. Population genomics: polymorphism and divergence allows more understanding of evolutionary forces: evolution, practical (disease frequency, genetic basis of human variation) Factors that influence patterns in genetic variation: mutation, natural selection. Random genetic drift (leads to loss of variation) Recombination: negative, positive (can reduce genetic variation, balancing selection (maintains diversity, migration and population history (influences spatial diversity) Approaches to the study of human genomic variation: snp typing. Problems: not a random sample, limited set of populations/individuals, ascertainment bias: pcr and resequencing. Less biased view but cannot be done on a large scale (impact on gene choice: whole genome sequencing.

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