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

Rebecca L. Lamason; Manzoor Ali P.K. Mohideen; Jason R. Mest; Andrew C. Wong; Heather L. Norton; Michele C. Aros; Michael J. Jurynec; Xianyun Mao; Vanessa R. Humphreville; Jasper E. Humbert; Soniya Sinha; Jessica L. Moore; Pudur Jagadeeswaran; Wei Zhao; Gang Ning; Izabela Makalowska; Paul M. McKeigue; David O'Donnell; Rick Kittles; Esteban J. Parra; Nancy J. Mangini; David J. Grunwald; Mark D. Shriver; Victor A. Canfield; Keith C. Cheng

doi:10.1126/science.1116238

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

Rebecca L. Lamason, Manzoor Ali P.K. Mohideen, Jason R. Mest, Andrew C. Wong, Heather L. Norton, Michele C. Aros, Michael J. Jurynec, Xianyun Mao, Vanessa R. Humphreville, Jasper E. Humbert, Soniya Sinha, Jessica L. Moore, Pudur Jagadeeswaran, Wei Zhao, Gang Ning, Izabela Makalowska, Paul M. McKeigue, David O'Donnell, Rick Kittles, Esteban J. ParraNancy J. Mangini, David J. Grunwald, Mark D. Shriver, Victor A. Canfield, Keith C. Cheng

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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.

Original language	English (US)
Pages (from-to)	1782-1786
Number of pages	5
Journal	Science
Volume	310
Issue number	5755
DOIs	https://doi.org/10.1126/science.1116238
State	Published - Dec 16 2005

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Lamason, R. L., Mohideen, M. A. P. K., 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., ... Cheng, K. C. (2005). Genetics: SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science, 310(5755), 1782-1786. https://doi.org/10.1126/science.1116238

Lamason, RL, Mohideen, MAPK, 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 2005, 'Genetics: SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans', Science, vol. 310, no. 5755, pp. 1782-1786. https://doi.org/10.1126/science.1116238

@article{2bd6c8f7eee54d759adb7c173db278d2,

title = "Genetics: 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.",

author = "Lamason, {Rebecca L.} and Mohideen, {Manzoor Ali P.K.} and Mest, {Jason R.} and Wong, {Andrew C.} and Norton, {Heather L.} and Aros, {Michele C.} and Jurynec, {Michael J.} and Xianyun Mao and Humphreville, {Vanessa R.} and Humbert, {Jasper E.} and Soniya Sinha and Moore, {Jessica L.} and Pudur Jagadeeswaran and Wei Zhao and Gang Ning and Izabela Makalowska and McKeigue, {Paul M.} and David O'Donnell and Rick Kittles and Parra, {Esteban J.} and Mangini, {Nancy J.} and Grunwald, {David J.} and Shriver, {Mark D.} and Canfield, {Victor A.} and Cheng, {Keith C.}",

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T2 - SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans

AU - Lamason, Rebecca L.

AU - Mohideen, Manzoor Ali P.K.

AU - Mest, Jason R.

AU - Wong, Andrew C.

AU - Norton, Heather L.

AU - Aros, Michele C.

AU - Jurynec, Michael J.

AU - Mao, Xianyun

AU - Humphreville, Vanessa R.

AU - Humbert, Jasper E.

AU - Sinha, Soniya

AU - Moore, Jessica L.

AU - Jagadeeswaran, Pudur

AU - Zhao, Wei

AU - Ning, Gang

AU - Makalowska, Izabela

AU - McKeigue, Paul M.

AU - O'Donnell, David

AU - Kittles, Rick

AU - Parra, Esteban J.

AU - Mangini, Nancy J.

AU - Grunwald, David J.

AU - Shriver, Mark D.

AU - Canfield, Victor A.

AU - Cheng, Keith C.

PY - 2005/12/16

Y1 - 2005/12/16

N2 - 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.

AB - 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.

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

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