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Eur J Hum Genet. 2012 Dec;20(12):1320-2. doi: 10.1038/ejhg.2012.68. Epub 2012 Apr 18.

Quantifying harmful mutations in human populations.

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  • Environmental Futures Centre and Australian Rivers Institute, School of Environment, Griffith University, Nathan, Qld, Australia. s.subramanian@griffith.edu.au


A number of previous studies suggested the presence of deleterious amino acid altering nonsynonymous single-nucleotide polymorphisms (nSNPs) in human populations. However, the proportions of deleterious nSNPs among rare and common variants are not known. To estimate these, >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.

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