Linkage and association analysis of spectrophotometrically quantified hair color in Australian adolescents: the effect of OCA2 and HERC2.
Genetic studies of pigmentation have benefited from spectrophotometric measures of light-dark hair color. Here we use one of those measures, absorbance at 650 nm, to look for chromosomal regions that harbor genes affecting hair pigmentation. At 7p15.1, marker D7S1808 was suggestive of linkage to light-dark hair color (LOD approximately 2.99). Marker D1S235 at 1q42.3 was suggestive of linkage to hair color (light-dark or blonde-black continuum) (LOD approximately 2.14). However, the most consistent linkage peak was over the gene oculocutaneous albinism type II (OCA2) on chromosome 15. Linkage analysis of both spectrophotometrically quantified and ordered ratings of hair color had LOD scores about 1.2, significant because of the almost perfect concordance. A quantitative transmission disequilibrium test between light-dark hair color and 58 single nucleotide polymorphisms in OCA2 showed that the SNPs rs4778138 (also called rs11855019) and rs1375164 were associated with significantly darker hair color (P approximately 3 x 10(-4) and P approximately 0.03 after correction for multiple testing, respectively). These two SNPs explain 1.54 and 0.85% of variation in the A650t index, respectively.
Shekar
Sri N
SN
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Duffy
David L
DL
Frudakis
Tony
T
Sturm
Richard A
RA
Zhao
Zhen Z
ZZ
Montgomery
Grant W
GW
Martin
Nicholas G
NG
D000293:Adolescent; D001315:Australia; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006200:Hair Color / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D010858:Pigmentation / Q000235:genetics; D013053:Spectrophotometry / Q000379:methods*; D044767:Ubiquitin-Protein Ligases
D020662:Guanine Nucleotide Exchange Factors; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C118566:HERC2 protein, human; D044767:Ubiquitin-Protein Ligases