PMID- 10101176
OWN - NLM
STAT- MEDLINE
DCOM- 19990512
LR  - 20220228
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 151
IP  - 4
DP  - 1999 Apr
TI  - High polymorphism at the human melanocortin 1 receptor locus.
PG  - 1547-57
AB  - Variation in human skin/hair pigmentation is due to varied amounts of eumelanin
      (brown/black melanins) and phaeomelanin (red/yellow melanins) produced by the
      melanocytes. The melanocortin 1 receptor (MC1R) is a regulator of eu- and
      phaeomelanin production in the melanocytes, and MC1R mutations causing coat color
      changes are known in many mammals. We have sequenced the MC1R gene in 121
      individuals sampled from world populations with an emphasis on Asian populations.
      We found variation at five nonsynonymous sites (resulting in the variants
      Arg67Gln, Asp84Glu, Val92Met, Arg151Cys, and Arg163Gln), but at only one
      synonymous site (A942G). Interestingly, the human consensus protein sequence is
      observed in all 25 African individuals studied, but at lower frequencies in the
      other populations examined, especially in East and Southeast Asians. The
      Arg163Gln variant is absent in the Africans studied, almost absent in Europeans, 
      and at a low frequency (7%) in Indians, but is at an exceptionally high frequency
      (70%) in East and Southeast Asians. The MC1R gene in common and pygmy
      chimpanzees, gorilla, orangutan, and baboon was sequenced to study the evolution 
      of MC1R. The ancestral human MC1R sequence is identical to the human consensus
      protein sequence, while MC1R varies considerably among higher primates. A
      comparison of the rates of substitution in genes in the melanocortin receptor
      family indicates that MC1R has evolved the fastest. In addition, the nucleotide
      diversity at the MC1R locus is shown to be several times higher than the average 
      nucleotide diversity in human populations, possibly due to diversifying
      selection.
FAU - Rana, B K
AU  - Rana BK
AD  - Human Genetics Center, School of Public Health and Graduate School of Biomedical 
      Sciences, University of Texas, Houston, Texas 77030, USA.
FAU - Hewett-Emmett, D
AU  - Hewett-Emmett D
FAU - Jin, L
AU  - Jin L
FAU - Chang, B H
AU  - Chang BH
FAU - Sambuughin, N
AU  - Sambuughin N
FAU - Lin, M
AU  - Lin M
FAU - Watkins, S
AU  - Watkins S
FAU - Bamshad, M
AU  - Bamshad M
FAU - Jorde, L B
AU  - Jorde LB
FAU - Ramsay, M
AU  - Ramsay M
FAU - Jenkins, T
AU  - Jenkins T
FAU - Li, W H
AU  - Li WH
LA  - eng
SI  - GENBANK/AF153431
SI  - GENBANK/AF153432
SI  - GENBANK/AF153433
SI  - GENBANK/AF153434
SI  - GENBANK/AF153435
SI  - GENBANK/AF153436
SI  - GENBANK/AF153437
GR  - GM30998/GM/NIGMS NIH HHS/United States
GR  - GM55759/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
RN  - 0 (DNA Primers)
RN  - 0 (Receptors, Corticotropin)
RN  - 0 (Receptors, Melanocortin)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Blacks/genetics
MH  - Consensus Sequence
MH  - DNA/genetics
MH  - DNA Primers/genetics
MH  - Evolution, Molecular
MH  - Gene Frequency
MH  - Genetic Variation
MH  - Hair Color/genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Polymorphism, Genetic
MH  - Primates
MH  - Receptors, Corticotropin/*genetics
MH  - Receptors, Melanocortin
MH  - Sequence Homology, Amino Acid
MH  - Skin Pigmentation/genetics
PMC - PMC1460552
EDAT- 1999/04/02 00:00
MHDA- 1999/04/02 00:01
CRDT- 1999/04/02 00:00
PHST- 1999/04/02 00:00 [pubmed]
PHST- 1999/04/02 00:01 [medline]
PHST- 1999/04/02 00:00 [entrez]
AID - 10.1093/genetics/151.4.1547 [doi]
PST - ppublish
SO  - Genetics. 1999 Apr;151(4):1547-57. doi: 10.1093/genetics/151.4.1547.