title: Human allelic variation: perspective from protein function, structure, and evolution.
abstract: It is widely anticipated that the coming year will be marked by the complete characterization of DNA sequence of protein-coding regions of thousands of human individuals. A number of existing computational methods use comparative protein sequence analysis and analysis of protein structure to predict the functional effect of coding human alleles. Functional and structural analysis of coding allelic variants can inform various aspects of research on human genetic variation. In population and evolutionary genetics it helps estimate the strength of purifying selection against deleterious missense mutations and study the imprint of demographic history on deleterious genetic variation. In medical genetics it may assist in the interpretation of uncharacterized mutations in genes involved in monogenic and oligogenic diseases. It has a potential to facilitate medical sequencing studies searching for genes underlying Mendelian diseases or harboring rare alleles involved in complex traits.
authors.affiliation: Division of Genetics, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Jordan
authors.forename: Vasily E
authors.initials: VE
authors.lastname: Ramensky
authors.forename: Shamil R
authors.initials: SR
authors.lastname: Sunyaev
mesh_terms: D000483:Alleles; D000818:Animals; D001185:Artificial Intelligence; D019143:Evolution, Molecular; D006801:Humans; D008511:Medicine; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins
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