title: Analysis of 15 primary open-angle glaucoma families from Australia identifies a founder effect for the Q368STOP mutation of myocilin.
abstract: Primary open-angle glaucoma (POAG) is a leading cause of blindness in the world. A number of mutations in the myocilin gene have been identified that predispose to glaucoma. The most frequent of these is the Glutamine368STOP (Q368STOP) mutation. It has been postulated that individuals with the Q368STOP mutation are derived from a common founder. To clarify this situation, we studied 15 unrelated POAG families who carried the Q368STOP mutation, from south eastern Australia. In one large family, nine affected and ten unaffected individuals were identified with the Q368STOP mutation. Closely linked polymorphic microsatellite markers were used to establish a disease haplotype in this family. Additional genotyping of markers in another 14 unrelated Q368STOP families revealed the presence of the same disease haplotype. These findings indicate that the Q368STOP mutation in all 15 families shared a common origin prior to the European settlement of Australia in the early 1800s.
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, 32 Gisborne Street, East Melbourne, Victoria 3002, Australia. pnb@unimelb.edu.au
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Richardson
authors.forename: Maree A
authors.initials: MA
authors.lastname: Ring
authors.forename: Pamela
authors.initials: P
authors.lastname: Sim
authors.forename: Sue
authors.initials: S
authors.lastname: Stanwix
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foote
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
mesh_terms: D000483:Alleles; D018388:Codon, Terminator / Q000235:genetics; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D005973:Glutamine / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016350:Leucine Zippers; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013021:South Australia; D000099179:Myocilin
chemical_list: D018388:Codon, Terminator; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D005136:Eye Proteins; D005973:Glutamine; D006023:Glycoproteins; D000099179:Myocilin