Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects.
The extension locus has been identified in many mammalian species as a gene that determines the relative amounts of eumelanin and phaeomelanin pigments in hair and skin. In at least three species, this locus has been demonstrated to encode the melanocyte-stimulating hormone receptor (MC1-R), and functionally variant alleles have been demonstrated to cause a broad range of pigmentation phenotypes. To test for MC1-R allelic variation in man, genomic DNA was extracted from skin samples collected from patients with different skin types (I-VI), and eye and hair color. A PCR-based approach was used to amplify the full-length coding sequence of the MC1-R and the resulting products were sequenced. Two polymorphic alleles were identified with single point mutations in the coding sequence: a valine-to-methionine substitution at position 92 (V92M), and an aspartic acid-to-glutamic acid substitution at position 84 (D84E). RFLP analysis demonstrated the presence of the V92M allele in 4 out of 60 (6.6%) of individuals examined, predominantly those with blue eyes and blond hair. This polymorphism was found in both heterozygous and homozygous states in individuals with type I skin. The D84E allele was found in one individual with skin type I; this person also has the V92 M allele and thus is a compound heterozygote.
Koppula
S V
SV
Vollum Institute for Advanced Biomedical Research, Portland, Oregon 97201, USA.
Robbins
L S
LS
Lu
D
D
Baack
E
E
White
C R
CR
Swanson
N A
NA
Cone
R D
RD
D000595:Amino Acid Sequence; D005127:Eye Color / Q000235:genetics; D006200:Hair Color / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011979:Receptors, Pituitary Hormone / Q000235:genetics*
D011979:Receptors, Pituitary Hormone; C029446:MSH receptor