A polymorphism study of the human Agouti gene and its association with MC1R

To determine whether the Agouti Signalling Protein (ASP) gene is associated with skin and hair coloration in humans, the complete coding region of ASP was screened for polymorphisms. Analysis of ASP in Caucasian, African-Amer ican, Spanish Basque, Hispanic, Apache and Australian Aboriginal population s revealed no amino acid substitutions. A single polymorphism in the 3' unt ranslated region occurred at a frequency of 0.2 in African-Americans. Varia nts of the Melanocortin 1 Receptor (MC1R) gene have been found to be associ ated with red hair and fair skin in humans. Red hair individuals are usuall y compound heterozygotes or homozygous for one of a number of MC1R polymorp hisms associated with red hair. Some individuals however are heterozygous f or only one of these polymorphisms and dizygotic twins can be concordant fo r MC1R variants but discordant for hair colour. A recent study has also ide ntified rare redheads carrying no MC1R variants indicating that polymorphis ms of the human MC1R gene are required but not sufficient for the red hair phenotype. To address the question of whether ASP also contributes to the r ed hair phenotype, individuals previously identified as having unexpected M C1R genotypes were screened for polymorphisms at the ASP locus. No polymorp hisms were found in any of these individuals. Results indicate that the hum an ASP gene is unlikely to function in normal human pigmentation in the sam e way as MC1R.