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Cited by 346melanin and skin pigmentationGenetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and Animals

The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.

Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression

Eiberg, Hans, Troelsen, Jesper, Nielsen, Mette, Mikkelsen, Annemette, Mengel-From, Jonas, Kjaer, Klaus W., Hansen, Lars·2008·Human Genetics
DOI 10.1007/s00439-007-0460-x
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Abstract

The human eye color is a quantitative trait displaying multifactorial inheritance. Several studies have shown that the OCA2 locus is the major contributor to the human eye color variation. By linkage analysis of a large Danish family, we finemapped the blue eye color locus to a 166 Kbp region within the HERC2 gene. By association analyses, we identified two SNPs within this region that were perfectly associated with the blue and brown eye colors: rs12913832 and rs1129038. Of these, rs12913832 is located 21.152 bp upstream from the OCA2 promoter in a highly conserved sequence in intron 86 of HERC2. The brown eye color allele of rs12913832 is highly conserved throughout a number of species. As shown by a Luciferase assays in cell cultures, the element significantly reduces the activity of the OCA2 promoter and electrophoretic mobility shift assays demonstrate that the two alleles bind different subsets of nuclear extracts. One single haplotype, represented by six polymorphic SNPs covering half of the 3' end of the HERC2 gene, was found in 155 blue-eyed individuals from Denmark, and in 5 and 2 blue-eyed individuals from Turkey and Jordan, respectively. Hence, our data suggest a common founder mutation in an OCA2 inhibiting regulatory element as the cause of blue eye color in humans. In addition, an LOD score of Z = 4.21 between hair color and D14S72 was obtained in the large family, indicating that RABGGTA is a candidate gene for hair color.

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Metadata

Authors
Eiberg, H., Troelsen, J., Nielsen, M., Mikkelsen, A., Mengel-From, J., Kjaer, K. W., & Hansen, L.
Affiliations
University of Copenhagen (DK)
Corresponding author
Eiberg, Hans
ORCID
Venue
Human Genetics
Publisher
Springer Science and Business Media LLC
Published
2008-01-03
Volume
123
Issue
2
Pages
177-187
ISSN
  • 0018-7348 (ISSN-L)
  • 0340-6717
  • 1432-1203
DOI
10.1007/s00439-007-0460-x
OpenAlex
W2103578460
Cited by
346
References
30
Citations by year
2026: 11 · 2025: 11 · 2024: 12 · 2023: 18 · 2022: 18 · 2021: 18 · 2020: 23 · 2019: 17 · 2018: 24 · 2017: 17 · 2016: 20 · 2015: 21 · 2014: 30 · 2013: 18 · 2012: 23
FWCI
9.49
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Human Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
HERC2, OCA2, founder mutation, regulatory elements, single nucleotide polymorphisms, haplotypes, eye color inheritance, hair color, conserved sequences
MeSH terms
Adult, Alleles, Cells, Cultured, Chromosomes, Human, Pair 15, Denmark, Eye Color, Female, Gene Expression Regulation, Genotype, Hair Color, Haplotypes, Humans, Genetic Linkage, Lod Score, Luciferases, Male, Mutation, Pedigree, Surveys and Questionnaires, Regulatory Sequences, Nucleic Acid, Founder Effect, Polymorphism, Single Nucleotide, Guanine Nucleotide Exchange Factors, Membrane Transport Proteins, Ubiquitin-Protein Ligases

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