title: A new polymorphism in the human factor VIII gene: implications for linkage analysis in haemophilia A and for the evolution of int22h sequences.
abstract: A new polymorphism in the human factor VIII gene has been localized and characterized. It is a biallelic, single nucleotide polymorphism located in intron 22 of the gene, within the 9.5 kb int22h-1 segment. The allelic forms are G (frequency 0.65) and A (frequency 0.35), giving a predicted rate of heterozygosity of 0.46. The polymorphism occurs within a CG dinucleotide and affects an MspI site (CCGG). Int22h-1 is duplicated twice extragenically at Xq28; both extragenic copies (int22h-2 and -3) are also polymorphic with respect to MspI. Investigation of 156 MspI [-] alleles, comprising 30 intragenic and 126 extragenic sites, indicated that all were due to A alleles and none had arisen by C to T transition within the CG dinucleotide. The intragenic MspI site (designated MspI A) is located 737 bases downstream of a previously described XbaI restriction fragment length polymorphism. Despite their close proximity, the polymorphisms are not in complete linkage disequilibrium; haplotype analysis in 85 factor VIII genes from a Caucasian population predicts an informativity of approximately 60% in linkage studies using both, compared with an informativity of approximately 47% in studies using either on its own.
authors: The Arthur Bloom Centre for Haemophilia and Haemostasis, Department of Haematology, University of Wales College of Medicine, Cardiff, South Wales, UK. bowendj1@cf.ac.uk
authors: D J
authors: DJ
authors: Bowen
authors: C D
authors: CD
authors: De Brasi
authors: I B
authors: IB
authors: Larripa
authors: P W
authors: PW
authors: Collins
mesh_terms: D002874:Chromosome Mapping; D019143:Evolution, Molecular; D005169:Factor VIII / Q000235:genetics*; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005838:Genotype; D006467:Hemophilia A / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014852:Wales
chemical_list: D005169:Factor VIII