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Allele frequencies of variants in Ultra Conserved Elements identify selective pressure on transcription factor binding

Silla, Toomas; Kepp, Katrin; Tai, E. Shyong; Goh, Liang; Davila, Sonia; Catela Ivković, Tina; Calin, George A.; Voorhoeve, P. Mathijs (2014) Allele frequencies of variants in Ultra Conserved Elements identify selective pressure on transcription factor binding. PLoS ONE, 9 (11). e110692/1-e110692/9. ISSN 1932-6203

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Ultra-conserved genes or elements (UCGs/UCEs) in the human genome are extreme examples of conservation. We characterized natural variations in 2884 UCEs and UCGs in two distinct populations ; Singaporean Chinese (n=280) and Italian (n=501) by using a pooled sample, targeted capture, sequencing approach. We identify, with high confidence, in these regions the abundance of rare SNVs (MAF<0.5%) of which 75% is not present in dbSNP137. UCEs association studies for complex human traits can use this information to model expected background variation and thus necessary power for association studies. By combining our data with 1000 Genome Project data, we show in three independent datasets that prevalent UCE variants (MAF>5%) are more often found in relatively less-conserved nucleotides within UCEs, compared to rare variants. Moreover, prevalent variants are less likely to overlap transcription factor binding site. Using SNPfold we found no significant influence of RNA secondary structure on UCE conservation. All together, these results suggest UCEs are not under selective pressure as a stretch of DNA but are under differential evolutionary pressure on the single nucleotide level.

Item Type: Article
Uncontrolled Keywords: UCGs; UCEs; sequencing
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Molekularna genetika i farmakogenetika gastrointestinalnih tumora[200570] Sanja Kapitanović098-0982464-2508MZOS
Depositing User: Tina Catela Ivković
Date Deposited: 09 Jul 2015 12:29
DOI: 10.1371/journal.pone.0110692

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