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

Human Genetics

Volumn 123, Issue 2, 2008, Pages 177-187

  Eiberg, Hans ^a   Troelsen, Jesper ^a   Nielsen, Mette ^a   Mikkelsen, Annemette ^a   Mengel From, Jonas ^b   Kjaer, Klaus W ^a,b   Hansen, Lars ^a,b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; LUCIFERASE; OCULOCUTANEOUS ALBINISM 2 PROTEIN; PROTEIN HERC2; UNCLASSIFIED DRUG;

3' UNTRANSLATED REGION; ANIMAL CELL; ARTICLE; CELL CULTURE; CONTROLLED STUDY; DENMARK; EYE COLOR; FAMILY; FEMALE; FOUNDER EFFECT; GEL MOBILITY SHIFT ASSAY; GENE ACTIVITY; GENE EXPRESSION REGULATION; GENE LOCATION; GENE LOCUS; GENE MAPPING; GENE MUTATION; GENETIC ASSOCIATION; HAIR COLOR; HAPLOTYPE; HUMAN; HUMAN CELL; INTRON; JORDAN; LINKAGE ANALYSIS; MALE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROMOTER REGION; REGULATOR GENE; SINGLE NUCLEOTIDE POLYMORPHISM; TURKEY (REPUBLIC);

ADULT; ALLELES; CELLS, CULTURED; CHROMOSOMES, HUMAN, PAIR 15; DENMARK; EYE COLOR; FEMALE; FOUNDER EFFECT; GENE EXPRESSION REGULATION; GENOTYPE; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HAIR COLOR; HAPLOTYPES; HUMANS; LINKAGE (GENETICS); LOD SCORE; LUCIFERASES; MALE; MEMBRANE TRANSPORT PROTEINS; MUTATION; PEDIGREE; POLYMORPHISM, SINGLE NUCLEOTIDE; QUESTIONNAIRES; REGULATORY SEQUENCES, NUCLEIC ACID;

NEMOPHILA; PSEUDOMUGILIDAE;

EID: 39549097952     PISSN: 03406717     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00439-007-0460-x     Document Type: Article

References (27)

1. Ancans J, Tobin DJ, Hoogduijn MJ, Smit NP, Wakamatsu K, Thody AJ (2001). Melanosomal pH controls rate of melanogenesis, eumelanin/phaeomelanin ratio and melanosome maturation in melanocytes and melanoma cells. Exp Cell Res 268:26-35
2. Carter D, Chakalova L, Osborne CS, Dai Y-F, Fraser P (2002). Long-range chromatin regulatory interactions in vivo. Nat Genet 32:623-626
3. Cavalli-Sforza LL, Menozzi P, Piazza A (1994). The History and geography of Human genes. Princeton University Press, Princeton
4. Duffy DL, Box NF, Chen W, Palmer JS, Montgomery GW, James MR, Hayward NK, Nicholas G, Martin NG, Sturm RA (2007). A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet 80:241-252
5. Eiberg H, Mohr J (1996). Assignment of genes coding for brown eye colour (BEY2) and brown hair colour (HCL3) on chromosome 15q. Eur J Hum Genet 4:237-241
6. Eiberg H, Nielsen LS, Klausen J, Dahlén M, Kristensen M, Bisgaard ML, Møller N, Mohr J (1989). Linkage between serum cholinesterase 2 (CHE2) and δ-crystalline gene cluster (CRYG): Assignment to chromosome 2. Clin Genet 35:313-321
7. Frudakis T, Thomas M, Gaskin Z, Venkateswarlu K, Chandra KS, Ginjupalli S, Gunturi S, Natrajan S, Ponnuswamy VK, Ponnuswamy KN (2003). Sequences associated with Human iris pigmentation. Genetics 165:2071-2083
8. Frudakis T, Terravainen T, Thomas M (2007) Multilocus OCA2 genotypes specify human iris colors. Hum Genet 122:311-326. doi: 10.1007/ s00439-007-0401-8
9. Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel AE, Kel OV, Ignatieva EV, Ananko EA, Podkolodnaya OA, Kolpakov FA et al (1998) Databases on transcriptional regulation: TRANSFAC, TRRD, and COMPEL. Nucleic Acids Res 26:364-370
10. Lamoreux ML, Zhou BK, Rosemblat S, Orlow SJ (1995) The pinkeyed-dilution protein and the eumelanin/pheomelanin switch: In support of a unifying hypothesis. Pigment Cell Res 8:263-270
11. Lee ST, Nicholls RD, Jong MT, Fukai K, Spritz RA (1995). Organization and sequence of the human P gene and identification of a new family of transport proteins. Genomics 20:354-63
12. Lehman AL, Nakatsu Y, Ching A, Bronson RT, Oakey RJ, Keiper-Hrynko N, Finger JN, Durham-Pierre D, Horton DB (1998) A very large protein with diverse functional motifs is deficient in rjs (runty, jerky, sterile) mice. Proc Natl Acad Sci USA 95:9436-9441
13. Myant NB, Fobes SA, Day INM, Gallagher J (1997) Estimation of the age of Ancestral Argenine 3500 → Glutamine mutation in Human ApoB-100. Genomic 45:78-87
14. Novak EK, Reddington M, Zhen L, Stenberg PE, Jackson CW, McGarry MP, Swank RT (1995) Inherited thrombocytopenia caused by reduced platelet production in mice with the gunmetal pigment gene mutation. Blood 85:1781-1789
15. Posthuma D, Visscher PM, Willemsen G, Zhu G, Martin NG, Slagboom PE, de Geus EJ, Boomsma DI (2006). Replicated linkage for eye color on 15q using comparative ratings of sibling pairs. Behav Genet 36:12-17
16. Puri N, Gardner JM, Brilliant MH (2000). Aberrant pH of melanosomes in pink-eyed dilution (P) mutant melanocytes. J Invest Dermatol 115:607-613
17. Rebbeck TR, Kanetsky PA, Walker AH, Holmes R, Halpern AC, Schuchter LM, Elder DE, Guerry D (2002). P gene as an inherited biomarker of human eye color. Cancer Epidemiol Biomarkers Prev 11:782-784
18. Remenyi A, Scholer HR, Wilmanns M (2004). Combinatorial control of gene expression. Nat Struct Mol Biol 11:812-815
19. Russell LB, Montgomery CS, Casheiro NLA, Johnaso DK (1995) Complementation analysis of 45 mutations encompassing the pink-eyed dilution locus of the mouse. Genetics 141:1547-1562
20. Schäffer AA, Gupta SK, Shriram K, Cottingham RW Jr (1994). Recomputation in linkage analysis. Hum Hered 44:225-237
21. Spritz RA, Bailin T, Nicholls RD, Lee ST, Park SK, Mascari MJ, Butler MG (1997). Hypopigmentation in the Prader-Willi syndrome correlates with P gene deletion but not with haplotype of the hemizygous P allele. Am J Med Genet 71:57-62
22. Sturm RA, Teasdale RD, Box NF (2001) Human pigmentation genes; identification, structure and consequences of polymorphic variation. Gene 277:49-62
23. Toyofuku K, Valencia JC, Kushimoto T, Costin GE, Virador VM, Vieira WD, Ferrans VJ, Hearing VJ (2002). The etiology of oculocutaneous albinism (OCA) type II: The pink protein modulates the processing and transport of tyrosinase. Pigment Cell Res 5:217-224
24. Troelsen JT, Mitchelmore C, Olsen J (2003a) An enhancer activates the pig lactase phlorizin hydrolase promoter in intestinal cells. Gene 305:101-111
25. Troelsen JT, Olsen J, Møller J, Sjöström H (2003b). An upstream polymorphism associated with lactase persistence has increased enhancer activity. Gastroenterology 125:1686-1694
26. Yonggang J, Rebert NA, Joslin JM, Higgins J, Schultz RA, Nicholls RD (2000). Structure of the highly conserved HERC2 gene and of multiple partially duplicated paralogs in Human. Genome Res 10:319-329
27. Zhu G, Evans DM, Duffy DL, Montgomery GW, Medland SE, Gillespie NA, Ewen KR, Jewell M, Liew YW, Hayward NK, et al (2004). A genome scan for eye color in 502 twin families: Most variation is due to a QTL on chromosome 15q. Twin Res 7:197-210