${session.getAttribute("locale")} 5 Temporal trails of natural selection in human mitogenomes Tue 16 Oct 2018 12:03:03 AEST ]]> Fixation of deleterious mutations at critical positions in human proteins Tue 16 Oct 2018 11:13:04 AEST ]]> High proportions of deleterious polymorphisms in constrained human genes 14,000 human-chimp nuclear genes and 1 million SNPs from four human genomes showed a significant proportion of deleterious nonsynonymous SNPs (∼15%). Importantly, this study reveals a negative correlation between the magnitude of selection pressure and the proportion of deleterious SNPs on human genes. The proportion of deleterious amino acid replacement polymorphisms is 3.5 times higher in genes under high purifying selection compared with that in less constrained genes (28% vs. 8%). These results are explained by differences in the extent of contribution of mildly deleterious mutations to diversity and substitution. © 2010 The Author.]]> Tue 16 Oct 2018 11:12:55 AEST ]]> Quantifying harmful mutations in human populations 77 000 SNPs from human protein-coding genes were analyzed. Based on two independent methods, this study reveals that up to 53% of rare nSNPs (minor allele frequency (MAF)<0.002) could be deleterious in nature. The fraction of deleterious nSNPs declines with the increase in their allele frequencies and only 12% of the common nSNPs (MAF>0.4) were found to be harmful. This shows that even at high frequencies significant fractions of deleterious polymorphisms are present in human populations. These results could be useful for genome-wide association studies in understanding the relative contributions of rare and common variants in causing human genetic diseases. © 2012 Macmillan Publishers Limited All rights reserved.]]> Tue 16 Oct 2018 11:12:22 AEST ]]>