title: Novel sequence elements define ancestral haplotypes of the region encompassing complement factor H.
abstract: The genomic region encompassing complement factor H (CFH) is thought to be important in determining susceptibility to inflammatory diseases such as age-related macular degeneration, but only limited polymorphism has been described. After applying the genomic matching technique to three-generation families and an ethnically diverse reference panel we have demonstrated that the polymorphism resembles that found in the major histocompatibility complex. The different ancestral haplotypes carry either T or C at T1277C but also other more polymorphic alleles over a region of 2 Mb. Thus the association between age-related macular degeneration and T1277 or Y402 actually reflects multiple linked polymorphisms including an indel that cannot be dissected from any direct effect of Y402 and may be more important. We show for the first time that simple algorithms can identify genomic sequence elements that appear to be more useful haplospecific markers than single nucleotide polymorphism or microsatellites.
authors.affiliation: CY O'Connor ERADE Village Foundation, Canning Vale, Western Australia.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Williamson
authors.forename: Craig A
authors.initials: CA
authors.lastname: McLure
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.forename: Dean
authors.initials: D
authors.lastname: Male
authors.forename: John
authors.initials: J
authors.lastname: Millman
authors.forename: Blair
authors.initials: B
authors.lastname: Lawley
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Ashdown
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Keating
authors.forename: Roger L
authors.initials: RL
authors.lastname: Dawkins
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers; D017242:Complement Factor H