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Insights into human biology from patterns of genetic variation

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Advances in DNA sequencing technology have now made whole-genome sequencing of human population samples feasible. The patterns of variation that we discover in our genomes provide information about the function of different types of genomic element, and about our evolutionary past. A small part of our genome (1-2%) codes for proteins, and these sequences generally show low levels of variation; many genetic disorders result from inactivation of a protein-coding gene. But surprisingly, we all carry inactivated forms of about 100 of these genes without apparent ill-effects. Systematic large-scale surveys of the consequences of inactivating almost all of genes are now under way. A large proportion of the rest of the genome influences gene expression, and the levels of variation in different classes of non-coding elements are beginning to provide information about the functional importance of this diverse and poorly-understood section of our genome. In addition, contrasting humans with other great apes reveals how exceptional humans are in their large numbers, wide geographical distribution and low but relatively uniform levels of genetic variation. Comparisons of patterns of variation in people from different continents suggests that these human characteristics are a consequence of an evolutionarily-recent expansion of modern humans 50-100 thousand years ago from a small population in Africa, and these patterns provide information about both the demographic changes and some of the adaptations to local environments that have accompanied this massive expansion.

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