title: Molecular and population genetic analysis of allelic sequence diversity at the human beta-globin locus.
abstract: Allelic sequence polymorphism at the beta-globin locus was investigated in a group of 36 Melanesians. A 3-kilobase fragment containing the gene and its flanking regions was sequenced in 60 normal (beta A) and 12 thalassemic (intron 1, position 5, G-->C) chromosomes. Haplotype relationships between linked polymorphisms were derived by allele-specific PCR amplification and sequencing. Seventeen nucleotide polymorphisms and 2 length variants were identified, and these sites segregated as 17 sequence haplotypes in the normal chromosomes. This haplotype diversity is higher than that expected on the basis of the nucleotide polymorphism observed and is probably due to recombination and gene conversion. Nucleotide diversity at synonymous sites in the sample is 0.14%, suggesting an average age of sequence divergence of approximately 450,000 years, consistent with that expected for a neutrally evolving human nuclear locus.
authors.affiliation: Medical Research Council Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Headington, United Kingdom.
authors.forename: S M
authors.initials: SM
authors.lastname: Fullerton
authors.forename: R M
authors.initials: RM
authors.lastname: Harding
authors.forename: A J
authors.initials: AJ
authors.lastname: Boyce
authors.forename: J B
authors.initials: JB
authors.lastname: Clegg
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005075:Biological Evolution; D044383:Black People / Q000235:genetics; D004247:DNA / Q000235:genetics; D014644:Genetic Variation; D005828:Genetics, Population; D005914:Globins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D012150:Polymorphism, Restriction Fragment Length; D009514:Vanuatu
chemical_list: D005914:Globins; D004247:DNA