文章基本信息

标题：The Dynamic Exome: acquired variants as individuals age
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作者：Jasmin H. Bavarva ; Hongseok Tae ; Lauren McIver 等
期刊名称：Aging
出版年度：2014
卷号：6
期号：6
页码：511-521
出版社：U.S.Department of Health & Human Service
摘要：A singular genome used for inference into population-based studies is a standard method in genomics. Recent studies show that spontaneous genomic variants can propagate into new generations and these changes can contribute to individual cell aging with environmental and evolutionary elements contributing to cumulative genomic variation. However, the contribution of aging to genomic changes in tissue samples remains uncharacterized. Here, we report the impact of aging on individual human exomes and their implications. We found the human genome to be dynamic, acquiring a varying number of mutations with age (5,000 to 50,000 in 9 to 16 years). This equates to a variation rate of 9.6x10^-7 to 8.4x10^-6bp^-1 year^-1 for nonsynonymous single nucleotide variants and 2.0x10^-4 to 1.0x10^-3locus^-1 year^-1 for microsatellite loci in these individuals. These mutations span across 3,000 to 13,000 genes, which commonly showed association with Wnt signaling and Gonadotropin releasing hormone receptor pathways, and indicated for individuals a specific and significant enrichment for increased risk for diabetes, kidney failure, cancer, Rheumatoid arthritis, and Alzheimer's disease- conditions usually associated with aging. The results suggest that "age" is an important variable while analyzing an individual human genome to extract individual-specific clinically significant information necessary for personalized genomics.
关键词：Aging; dynamic exome; exome sequencing; personalized genomics; personalized medicine