RT Journal Article SR Electronic T1 Positive selection in Europeans and East-Asians at the ABCA12 gene JF bioRxiv FD Cold Spring Harbor Laboratory SP 392811 DO 10.1101/392811 A1 Roberto Sirica A1 Marianna Buonaiuto A1 Valeria Petrella A1 Lucia Sticco A1 Donatella Tramontano A1 Dario Antonini A1 Caterina Missero A1 Ombretta Guardiola A1 Gennaro Andolfi A1 Heerman Kumar A1 Qasim Ayub A1 Yali Xue A1 Chris Tyler-Smith A1 Marco Salvemini A1 Giovanni D’Angelo A1 Vincenza Colonna YR 2018 UL http://biorxiv.org/content/early/2018/08/16/392811.abstract AB Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation.We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site of ABCA12. We found no obvious effect of rs10180970 alleles on ABCA12 gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and frequent among non-Africans already 45,000 years ago.