Identification of Gene Variants Associated with Melanocyte Stem Cell Differentiation in Mice Predisposed for Hair Graying

Age-related hair graying is caused by malfunction in the regenerative potential of the adult pigmentation system. The retention of hair color over the life of an organism is dependent on the ability of the melanocyte stem cells and their progeny to produce pigment each time a new hair grows. Age-rel...

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Published in:G3 : genes - genomes - genetics Vol. 9; no. 3; p. 817
Main Authors: Fialkowski, Allison C, Levy, Denise J, Watkins-Chow, Dawn E, Palmer, Joseph W, Darji, Roshan, Tiwari, Hemant K, Pavan, William J, Harris, Melissa L
Format: Journal Article
Language:English
Published: England 01-03-2019
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Abstract Age-related hair graying is caused by malfunction in the regenerative potential of the adult pigmentation system. The retention of hair color over the life of an organism is dependent on the ability of the melanocyte stem cells and their progeny to produce pigment each time a new hair grows. Age-related hair graying is variable in association with genetic background suggesting that quantitative trait loci influencing this trait can be identified. Identification of these quantitative trait loci may lead to the discovery of novel and interesting genes involved in stem cell biology and/or melanogenesis. With this in mind we developed previously a sensitized, mouse modifier screen and discovered that the DBA/1J background is particularly resistant to melanocyte stem cell differentiation in comparison to the C57BL/6J background. Melanocyte stem cell differentiation generally precedes hair graying and is observed in melanocyte stem cells with age. Using quantitative trait loci analysis, we have now identified three quantitative trait loci on mouse chromosomes 7, 13, and X that are associated with DBA/1J-mediated variability in melanocyte stem cell differentiation. Taking advantage of publicly-available mouse sequence and variant data, in silico protein prediction programs, and whole genome gene expression results we describe a short list of potential candidate genes that we anticipate to be involved in melanocyte stem cell biology in mice.
AbstractList Age-related hair graying is caused by malfunction in the regenerative potential of the adult pigmentation system. The retention of hair color over the life of an organism is dependent on the ability of the melanocyte stem cells and their progeny to produce pigment each time a new hair grows. Age-related hair graying is variable in association with genetic background suggesting that quantitative trait loci influencing this trait can be identified. Identification of these quantitative trait loci may lead to the discovery of novel and interesting genes involved in stem cell biology and/or melanogenesis. With this in mind we developed previously a sensitized, mouse modifier screen and discovered that the DBA/1J background is particularly resistant to melanocyte stem cell differentiation in comparison to the C57BL/6J background. Melanocyte stem cell differentiation generally precedes hair graying and is observed in melanocyte stem cells with age. Using quantitative trait loci analysis, we have now identified three quantitative trait loci on mouse chromosomes 7, 13, and X that are associated with DBA/1J-mediated variability in melanocyte stem cell differentiation. Taking advantage of publicly-available mouse sequence and variant data, in silico protein prediction programs, and whole genome gene expression results we describe a short list of potential candidate genes that we anticipate to be involved in melanocyte stem cell biology in mice.
Author Levy, Denise J
Harris, Melissa L
Palmer, Joseph W
Tiwari, Hemant K
Watkins-Chow, Dawn E
Fialkowski, Allison C
Darji, Roshan
Pavan, William J
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  givenname: Allison C
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  organization: Department of Biostatistics
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  givenname: Denise J
  surname: Levy
  fullname: Levy, Denise J
  organization: University of Alabama at Birmingham, Birmingham, AL, and
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  givenname: Dawn E
  surname: Watkins-Chow
  fullname: Watkins-Chow, Dawn E
  organization: University of Alabama at Birmingham, Birmingham, AL, and
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  givenname: Joseph W
  surname: Palmer
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  organization: Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
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  givenname: Roshan
  surname: Darji
  fullname: Darji, Roshan
  organization: Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
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  givenname: Hemant K
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  organization: Department of Biostatistics
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  fullname: Pavan, William J
  organization: University of Alabama at Birmingham, Birmingham, AL, and
– sequence: 8
  givenname: Melissa L
  surname: Harris
  fullname: Harris, Melissa L
  organization: Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
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Keywords modifier
QTL
hair graying
melanocyte stem cell
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Snippet Age-related hair graying is caused by malfunction in the regenerative potential of the adult pigmentation system. The retention of hair color over the life of...
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Title Identification of Gene Variants Associated with Melanocyte Stem Cell Differentiation in Mice Predisposed for Hair Graying
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