title: New polymorphic microsatellite markers place the haemochromatosis gene telomeric to D6S105.
abstract: The haemochromatosis gene (HFE) is linked to both HLA-A and D6S105 on the short arm of chromosome 6 but these markers are separated by approximately 2 Mb of DNA. Most chromosomes carrying HFE have a common haplotype which extends from HLA-A to D6S105 and includes HLA-F. To localise the gene more precisely we have examined 10 microsatellite markers extending over a genetic distance of approximately 5 cM from D6S265 (within 100 kb of HLA-A on the centromeric side) to D6S299 (telomeric). The order of markers is D6S265, HLA-F, D6S258, D6S306, CS3, D6S105, D6S464, CS5, D6S461 and D6S299. We confirm that haemochromatosis appears to originate from a founder mutation which has multiplied in the population through successive generations. This mutation is associated with the haplotype D6S306-5, CS3-3, D6S105-8, D6S464-9 and CS5-4 which is found on approximately 70% of HFE chromosomes. We have applied a new and powerful, likelihood analysis for linkage disequilibrium. The maximum value of lambda (proportion of total possible association between a marker and disease) is 0.74 for marker CS5 (allele 4). A multipoint analysis also gives a maximum likelihood near marker CS5. We conclude that the HFE gene is likely to be located telomeric of D6S105 and close to CS5.
authors.affiliation: Department of Haematology, University of Wales College of Medicine, Cardiff, UK.
authors.forename: R
authors.initials: R
authors.lastname: Raha-Chowdhury
authors.forename: D J
authors.initials: DJ
authors.lastname: Bowen
authors.forename: C
authors.initials: C
authors.lastname: Stone
authors.forename: J J
authors.initials: JJ
authors.lastname: Pointon
authors.forename: J D
authors.initials: JD
authors.lastname: Terwilliger
authors.forename: J D
authors.initials: JD
authors.lastname: Shearman
authors.forename: K J
authors.initials: KJ
authors.lastname: Robson
authors.forename: A
authors.initials: A
authors.lastname: Bomford
authors.forename: M
authors.initials: M
authors.lastname: Worwood
mesh_terms: D000483:Alleles; D001315:Australia; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D015234:HLA-A Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D011336:Probability; D016615:Telomere; D006113:United Kingdom; D014481:United States
chemical_list: D004276:DNA, Satellite; D005819:Genetic Markers; D015234:HLA-A Antigens