000195458 001__ 195458
000195458 005__ 20181203023407.0
000195458 0247_ $$2doi$$a10.1101/gr.154971.113
000195458 022__ $$a1088-9051
000195458 02470 $$2ISI$$a000327946900002
000195458 037__ $$aARTICLE
000195458 245__ $$aThe influence of genomic context on mutation patterns in the human genome inferred from rare variants
000195458 269__ $$a2013
000195458 260__ $$aCold Spring Harbor$$bCold Spring Harbor Lab Press, Publications Dept$$c2013
000195458 300__ $$a11
000195458 336__ $$aJournal Articles
000195458 520__ $$aUnderstanding patterns of spontaneous mutations is of fundamental interest in studies of human genome evolution and genetic disease. Here, we used extremely rare variants in humans to model the molecular spectrum of single-nucleotide mutations. Compared to common variants in humans and human-chimpanzee fixed differences (substitutions), rare variants, on average, arose more recently in the human lineage and are less affected by the potentially confounding effects of natural selection, population demographic history, and biased gene conversion. We analyzed variants obtained from a population-based sequencing study of 202 genes in >14,000 individuals. We observed considerable variability in the per-gene mutation rate, which was correlated with local GC content, but not recombination rate. Using >20,000 variants with a derived allele frequency >= 10(-4), we examined the effect of local GC content and recombination rate on individual variant subtypes and performed comparisons with common variants and substitutions. The influence of local GC content on rare variants differed from that on common variants or substitutions, and the differences varied by variant subtype. Furthermore, recombination rate and recombination hotspots have little effect on rare variants of any subtype, yet both have a relatively strong impact on multiple variant subtypes in common variants and substitutions. This observation is consistent with the effect of biased gene conversion or selection-dependent processes. Our results highlight the distinct biases inherent in the initial mutation patterns and subsequent evolutionary processes that affect segregating variants.
000195458 700__ $$aSchaibley, Valerie M.$$uUniv Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
000195458 700__ $$aZawistowski, Matthew$$uUniv Michigan, Dept Biostat, Ann Arbor, MI 48019 USA
000195458 700__ $$aWegmann, Daniel$$uEcole Polytech Fed Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland
000195458 700__ $$aEhm, Margaret G.$$uGlaxoSmithKline GSK, Dept Quantitat Sci, Res Triangle Pk, NC 27709 USA
000195458 700__ $$aNelson, Matthew R.$$uGlaxoSmithKline GSK, Dept Quantitat Sci, Res Triangle Pk, NC 27709 USA
000195458 700__ $$aSt Jean, Pamela L.$$uGlaxoSmithKline GSK, Dept Quantitat Sci, Res Triangle Pk, NC 27709 USA
000195458 700__ $$aAbecasis, Goncalo R.$$uUniv Michigan, Dept Biostat, Ann Arbor, MI 48019 USA
000195458 700__ $$aNovembre, John$$uUniv Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA
000195458 700__ $$aZoellner, Sebastian$$uUniv Michigan, Dept Biostat, Ann Arbor, MI 48019 USA
000195458 700__ $$aLi, Jun Z.$$uUniv Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
000195458 773__ $$j23$$k12$$q1974-1984$$tGenome Research
000195458 909C0 $$0252444$$pIBI
000195458 909CO $$ooai:infoscience.tind.io:195458$$particle$$pSV$$pSTI
000195458 937__ $$aEPFL-ARTICLE-195458
000195458 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000195458 980__ $$aARTICLE