Quantifying harmful mutations in human populations

View/ Open
Author(s)
Sankarasubramanian, Sankar
Griffith University Author(s)
Year published
2012
Metadata
Show full item recordAbstract
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 ...
View more >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.
View less >
View more >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.
View less >
Journal Title
European Journal of Human Genetics
Volume
20
Copyright Statement
© 2012 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
Subject
Molecular Evolution
Genetics
Clinical Sciences