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- W2989717253 abstract "Abstract Background Lymphotoxin-α ( LTα ), located in the Major Histocompatibility Complex (MHC) class III region on chromosome 6, encodes a cytotoxic protein that mediates a variety of antiviral responses among other biological functions. Furthermore, several genotypes at this gene have been implicated in the onset of a number of complex diseases, including myocardial infarction, autoimmunity, and various types of cancer. However, little is known about levels of nucleotide variation and linkage disequilibrium (LD) in and near LTα , which could also influence phenotypic variance. To address this gap in knowledge, we examined sequence variation across ~ 10 kilobases (kbs), encompassing LTα and the upstream region, in 2039 individuals from the 1000 Genomes Project originating from 21 global populations. Results Here, we observed striking patterns of diversity, including an excess of intermediate-frequency alleles, the maintenance of multiple common haplotypes and a deep coalescence time for variation (dating > 1.0 million years ago), in global populations. While these results are generally consistent with a model of balancing selection, we also uncovered a signature of positive selection in the form of long-range LD on chromosomes with derived alleles primarily in Eurasian populations. To reconcile these findings, which appear to support different models of selection, we argue that selective sweeps (particularly, soft sweeps) of multiple derived alleles in and/or near LTα occurred in non-Africans after their ancestors left Africa. Furthermore, these targets of selection were predicted to alter transcription factor binding site affinity and protein stability, suggesting they play a role in gene function. Additionally, our data also showed that a subset of these functional adaptive variants are present in archaic hominin genomes. Conclusions Overall, this study identified candidate functional alleles in a biologically-relevant genomic region, and offers new insights into the evolutionary origins of these loci in modern human populations." @default.
- W2989717253 created "2019-12-05" @default.
- W2989717253 creator A5056619936 @default.
- W2989717253 creator A5062092304 @default.
- W2989717253 creator A5070626604 @default.
- W2989717253 creator A5071166177 @default.
- W2989717253 creator A5081951768 @default.
- W2989717253 date "2019-12-01" @default.
- W2989717253 modified "2023-10-13" @default.
- W2989717253 title "Multiple selective sweeps of ancient polymorphisms in and around LTα located in the MHC class III region on chromosome 6" @default.
- W2989717253 cites W1535247537 @default.
- W2989717253 cites W1548753337 @default.
- W2989717253 cites W1558580462 @default.
- W2989717253 cites W1558762228 @default.
- W2989717253 cites W1572265772 @default.
- W2989717253 cites W1577010727 @default.
- W2989717253 cites W1607246558 @default.
- W2989717253 cites W1640614960 @default.
- W2989717253 cites W1872841669 @default.
- W2989717253 cites W1900337607 @default.
- W2989717253 cites W1935056412 @default.
- W2989717253 cites W1964547306 @default.
- W2989717253 cites W1965218239 @default.
- W2989717253 cites W1967279698 @default.
- W2989717253 cites W1969866404 @default.
- W2989717253 cites W1971397968 @default.
- W2989717253 cites W1976844960 @default.
- W2989717253 cites W1977334739 @default.
- W2989717253 cites W1979363808 @default.
- W2989717253 cites W1980674207 @default.
- W2989717253 cites W1983381955 @default.
- W2989717253 cites W1986447034 @default.
- W2989717253 cites W1987306970 @default.
- W2989717253 cites W1988544363 @default.
- W2989717253 cites W1997476591 @default.
- W2989717253 cites W1999623479 @default.
- W2989717253 cites W2006142399 @default.
- W2989717253 cites W2006853093 @default.
- W2989717253 cites W2009494639 @default.
- W2989717253 cites W2009610362 @default.
- W2989717253 cites W2010366972 @default.
- W2989717253 cites W2014909541 @default.
- W2989717253 cites W2016879826 @default.
- W2989717253 cites W2023490488 @default.
- W2989717253 cites W2025253353 @default.
- W2989717253 cites W2028704045 @default.
- W2989717253 cites W2029201460 @default.
- W2989717253 cites W2031783089 @default.
- W2989717253 cites W2038473742 @default.
- W2989717253 cites W2039323256 @default.
- W2989717253 cites W2039435867 @default.
- W2989717253 cites W2045955868 @default.
- W2989717253 cites W2046630500 @default.
- W2989717253 cites W2047495447 @default.
- W2989717253 cites W2047816292 @default.
- W2989717253 cites W2047888040 @default.
- W2989717253 cites W2051864455 @default.
- W2989717253 cites W2055543630 @default.
- W2989717253 cites W2057083103 @default.
- W2989717253 cites W2058516219 @default.
- W2989717253 cites W2062544659 @default.
- W2989717253 cites W2063999310 @default.
- W2989717253 cites W2064337222 @default.
- W2989717253 cites W2069216282 @default.
- W2989717253 cites W2069769149 @default.
- W2989717253 cites W2073621589 @default.
- W2989717253 cites W2075177151 @default.
- W2989717253 cites W2090433023 @default.
- W2989717253 cites W2096420865 @default.
- W2989717253 cites W2096791516 @default.
- W2989717253 cites W2097668177 @default.
- W2989717253 cites W2097791641 @default.
- W2989717253 cites W2098237519 @default.
- W2989717253 cites W2098460741 @default.
- W2989717253 cites W2100481775 @default.
- W2989717253 cites W2109441358 @default.
- W2989717253 cites W2109580010 @default.
- W2989717253 cites W2109763190 @default.
- W2989717253 cites W2111913661 @default.
- W2989717253 cites W2116187144 @default.
- W2989717253 cites W2117553956 @default.
- W2989717253 cites W2118780696 @default.
- W2989717253 cites W2120614958 @default.
- W2989717253 cites W2124362779 @default.
- W2989717253 cites W2127757090 @default.
- W2989717253 cites W2128016314 @default.
- W2989717253 cites W2129349128 @default.
- W2989717253 cites W2131424931 @default.
- W2989717253 cites W2132499964 @default.
- W2989717253 cites W2133298050 @default.
- W2989717253 cites W2133877466 @default.
- W2989717253 cites W2134599124 @default.
- W2989717253 cites W2135370544 @default.
- W2989717253 cites W2136513422 @default.
- W2989717253 cites W2136853376 @default.
- W2989717253 cites W2137303277 @default.
- W2989717253 cites W2137886330 @default.
- W2989717253 cites W2137903841 @default.
- W2989717253 cites W2138744193 @default.
- W2989717253 cites W2139974331 @default.