SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Lamason, Rebecca L; Mohideen, Manzoor-Ali P K; Mest, Jason R; Wong, Andrew C; Norton, Heather L; Aros, Michele C; Jurynec, Michael J; Mao, Xianyun; Humphreville, Vanessa R; Humbert, Jasper E; Sinha, Soniya; Moore, Jessica L; Jagadeeswaran, Pudur; Zhao, Wei; Ning, Gang; Makalowska, Izabela; McKeigue, Paul M; O'donnell, David; Kittles, Rick; Parra, Esteban J; Mangini, Nancy J; Grunwald, David J; Shriver, Mark D; Canfield, Victor A; Cheng, Keith C
Year of Publication: 2005
Journal: Science
Volume: 310
Issue: 5755
Pagination: 1782-6
Date Published: 2005 Dec 16
Publication Language: eng
ISSN: 1095-9203
Keywords: African Americans, African Continental Ancestry Group, Alanine, Alleles, Amino Acid Sequence, Animals, Antiporters, Asian Continental Ancestry Group, Biological Evolution, Calcium, European Continental Ancestry Group, Gene Frequency, Genes, Genetic Variation, Haplotypes, Heterozygote, Humans, Ion Transport, Melanins, Melanosomes, Mice, Molecular Sequence Data, Multifactorial Inheritance, Mutation, Pigment Epithelium of Eye, Polymorphism, Single Nucleotide, Selection, Genetic, Skin Pigmentation, Threonine, Zebrafish, Zebrafish Proteins

Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved ancestral allele of a human coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation.

DOI: 10.1126/science.1116238
Alternate Journal: Science
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