ZFIN ID: ZDB-PUB-051219-10
SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans
Lamason, R.L., Mohideen, M.A., Mest, J.R., Wong, A.C., Norton, H.L., Aros, M.C., Jurynec, M.J., Mao, X., Humphreville, V.R., Humbert, J.E., Sinha, S., Moore, J.L., Jagadeeswaran, P., Zhao, W., Ning, G., Makalowska, I., McKeigue, P.M., O'donnell, D., Kittles, R., Parra, E.J., Mangini, N.J., Grunwald, D.J., Shriver, M.D., Canfield, V.A., and Cheng, K.C.
Date: 2005
Source: Science (New York, N.Y.)   310(5755): 1782-1786 (Journal)
Registered Authors: Aros, Michele, Canfield, Victor, Cheng, Keith C., Grunwald, David, Humbert, Jasper, Jagadeeswaran, Pudur, Jurynec, Michael, Mest, Jason, Mohideen, Manzoor Pallithotangal, Moore, Jessica L., Sinha, Soniya, Wong, Andrew
Keywords: none
MeSH Terms:
  • African Americans/genetics
  • Alanine/genetics
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Antiporters/chemistry
  • Antiporters/genetics*
  • Antiporters/physiology
  • Asians/genetics
  • Biological Evolution
  • Blacks/genetics
  • Calcium/metabolism
  • Gene Frequency
  • Genes
  • Genetic Variation
  • Haplotypes
  • Heterozygote
  • Humans
  • Ion Transport
  • Melanins/analysis
  • Melanosomes/chemistry
  • Melanosomes/ultrastructure
  • Mice
  • Molecular Sequence Data
  • Multifactorial Inheritance
  • Mutation
  • Pigment Epithelium of Eye/chemistry
  • Pigment Epithelium of Eye/ultrastructure
  • Polymorphism, Single Nucleotide
  • Selection, Genetic
  • Skin Pigmentation/genetics*
  • Threonine/genetics
  • Whites/genetics
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology
PubMed: 16357253 Full text @ Science
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.