title: SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans.
abstract: 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.
authors.affiliation: Jake Gittlen Cancer Research Foundation, Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Lamason
authors.forename: Manzoor-Ali P K
authors.initials: MA
authors.lastname: Mohideen
authors.forename: Jason R
authors.initials: JR
authors.lastname: Mest
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Wong
authors.forename: Heather L
authors.initials: HL
authors.lastname: Norton
authors.forename: Michele C
authors.initials: MC
authors.lastname: Aros
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jurynec
authors.forename: Xianyun
authors.initials: X
authors.lastname: Mao
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Humphreville
authors.forename: Jasper E
authors.initials: JE
authors.lastname: Humbert
authors.forename: Soniya
authors.initials: S
authors.lastname: Sinha
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Moore
authors.forename: Pudur
authors.initials: P
authors.lastname: Jagadeeswaran
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Gang
authors.initials: G
authors.lastname: Ning
authors.forename: Izabela
authors.initials: I
authors.lastname: Makalowska
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKeigue
authors.forename: David
authors.initials: D
authors.lastname: O'donnell
authors.forename: Rick
authors.initials: R
authors.lastname: Kittles
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Parra
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Mangini
authors.forename: David J
authors.initials: DJ
authors.lastname: Grunwald
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: Victor A
authors.initials: VA
authors.lastname: Canfield
authors.forename: Keith C
authors.initials: KC
authors.lastname: Cheng
mesh_terms: D001741:Black or African American / Q000235:genetics; D000409:Alanine / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D044466:Asian People / Q000235:genetics; D005075:Biological Evolution; D044383:Black People / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D005787:Gene Frequency; D005796:Genes; D014644:Genetic Variation; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D017136:Ion Transport; D008543:Melanins / Q000032:analysis; D020460:Melanosomes / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D020412:Multifactorial Inheritance; D009154:Mutation; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000648:ultrastructure; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D012880:Skin Pigmentation / Q000235:genetics*; D013912:Threonine / Q000235:genetics; D044465:White People / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: D017920:Antiporters; D008543:Melanins; C506584:SLC24A5 protein, human; C506583:SLC24A5 protein, zebrafish; D029961:Zebrafish Proteins; D013912:Threonine; D000409:Alanine; D002118:Calcium