Identification of 127 amino acid substitution variants in screening 37 DNA repair genes in humans.

摘要: The repair of damaged DNA requires the function multiple proteins in generally damage-specific, nonredundant pathways. relationship to cancer susceptibility is obvious "cancer families," which low frequency, high penetrance, loss-of-function variant alleles genes with roles have been associated a risk disease. More important for incidence general population, many individuals exhibit reduced (60-75% normal) capacity phenotypes that several-fold increases individual risk. In program identify molecular basis variation and elevated susceptibility, we identified 127 amino acid substitution variants resequencing 37 36-164 unrelated individuals. Over 50% substitutions are exchanges residues dissimilar physical or chemical properties, at sites common residue identical human mouse proteins. Five additional sequence changes resulting altered termination translation one insertion were detected. allele frequencies average 0.047, ranging from <0.01 0.43. Homozygous gene observed. Most exhibited pathway. Ten accounted 52% genetic among individuals, but striking 23% total 108 less than 5%. Screening healthy generates catalogue resource epidemiology studies endeavoring use genotype phenotype paradigm estimate role disease environmental lifestyle exposures population United States.