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PMID: 16357253 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Science (New York, N.Y.) ·Vol. 310 ·No. 5755 ·2005-12-16 ·Pages 1782-6

Lamason RL, Mohideen MA, Mest JR, Wong AC, Norton HL, Aros MC, Jurynec MJ, Mao X, Humphreville VR, Humbert JE, Sinha S, Moore JL, Jagadeeswaran P, Zhao W, Ning G, Makalowska I, McKeigue PM, O'donnell D, Kittles R, Parra EJ, Mangini NJ, Grunwald DJ, Shriver MD, Canfield VA, Cheng KC

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.

MeSH Terms

African Americans/genetics Alanine/genetics Alleles Amino Acid Sequence Animals Antiporters/chemistry,genetics,physiology Asians/genetics Biological Evolution Blacks/genetics Calcium/metabolism Gene Frequency Genes Genetic Variation Haplotypes Heterozygote Humans Ion Transport Melanins/analysis Melanosomes/chemistry,ultrastructure Mice Molecular Sequence Data Multifactorial Inheritance Mutation Pigment Epithelium of Eye/chemistry,ultrastructure Polymorphism, Single Nucleotide Selection, Genetic Skin Pigmentation/genetics Threonine/genetics Whites/genetics Zebrafish/embryology,genetics,metabolism Zebrafish Proteins/chemistry,genetics,physiology

Chemicals

Antiporters Melanins SLC24A5 protein, human SLC24A5 protein, zebrafish Zebrafish Proteins Threonine Alanine Calcium

Authors & Affiliations

25 authors, click to expand affiliations / ORCID

Lamason Rebecca L

Jake Gittlen Cancer Research Foundation, Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

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

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1116238

Published

2005-12-16

Pages

1782-6

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NICHD NIH HHS · HD37572 · United States

NHGRI NIH HHS · HG002154 · United States

NCRR NIH HHS · RR017441 · United States

NICHD NIH HHS · R01 HD040179 · United States

NCI NIH HHS · CA73935 · United States

NICHD NIH HHS · HD40179 · United States

NHLBI NIH HHS · HL077910 · United States

NEI NIH HHS · EY11308 · United States

NCI NIH HHS · R01 CA131956 · United States

Corrections

CommentIn

PMID: 16357234

External Links

PubMed source DOI: 10.1126/science.1116238 View journal details

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

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