Loci associated with skin pigmentation identified in African populations.
Nicholas G CrawfordDerek E KellyMatthew E B HansenMarcia Holsbach BeltrameShaohua FanShanna L BowmanEthan JewettAlessia RanciaroSimon ThompsonYancy LoSusanne P PfeiferJeffrey D JensenMichael C CampbellWilliam BeggsFarhad HormozdiariSununguko Wata MpolokaGaonyadiwe George MokoneThomas NyamboDawit Wolde MeskelGurja BelayJake Hautnull nullHarriet T RothschildLeonard I ZonYi ZhouMichael A KovacsMai XuTongwu ZhangKevin BishopJason SinclairCecilia RivasEugene ElliotJiyeon ChoiShengchao A LiBelynda D HicksJason W SinclairChristian C AbnetDawn E Watkins-ChowElena OanceaYun S SongEleazar EskinKevin K BrownMichael S MarksStacie K LoftusWilliam J PavanMeredith YeagerStephen ChanockSarah A TishkoffPublished in: Science (New York, N.Y.) (2017)
Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5, MFSD12, DDB1, TMEM138, OCA2, and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in South Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of ultraviolet response genes under selection in Eurasians.
Keyphrases
- genome wide
- copy number
- dna methylation
- soft tissue
- wound healing
- poor prognosis
- genetic diversity
- transcription factor
- gene expression
- binding protein
- genome wide association study
- type diabetes
- insulin resistance
- genome wide analysis
- long non coding rna
- genome wide association
- amino acid
- high fat diet induced
- wild type