title: Refined mapping of the Usher syndrome type III locus on chromosome 3, exclusion of candidate genes, and identification of the putative mouse homologous region.
abstract: A locus for Usher syndrome type III (USH3; MIM No. 276902) was recently assigned to a 5-cM region on chromosome 3q. We constructed a yeast artificial chromosome contig that allowed us to position novel polymorphisms in the region. These were typed in a total of 32 pedigrees from a geographically isolated Finnish founder population in which a putative single ancestral USH3 mutation segregates. A multipoint linkage analysis assigned USH3 to a 4-cM region between D3S1555 and a novel marker D3S3625. By analysis of linkage disequilibrium and historical recombinations in 77 USH3 chromosomes, the location of the Finnish USH3 mutation could be narrowed to an approximately 1-cM interval between the markers D3S1299 and D3S3625. A gene for profilin-2 (PFN2) was mapped in the vicinity and excluded as a candidate for USH3 by sequencing. The putative mouse homolog of PFN2 was mapped to mouse chromosome 3, thus suggesting a localization for the mouse homolog of USH3.
authors.affiliation: Department of Medical Genetics, University of Helsinki, Finland. sankila@helsinki.fi
authors.forename: T
authors.initials: T
authors.lastname: Joensuu
authors.forename: G
authors.initials: G
authors.lastname: Blanco
authors.forename: L
authors.initials: L
authors.lastname: Pakarinen
authors.forename: P
authors.initials: P
authors.lastname: Sistonen
authors.forename: H
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Chapelle
authors.forename: E M
authors.initials: EM
authors.lastname: Sankila
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003285:Contractile Proteins; D005387:Finland / Q000453:epidemiology; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D051379:Mice / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics; D051304:Profilins; D012174:Retinitis Pigmentosa / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D017385:Sequence Homology; D013045:Species Specificity; D013577:Syndrome; D015837:Vestibular Diseases / Q000145:classification / Q000453:epidemiology / Q000235:genetics*
chemical_list: D003285:Contractile Proteins; D008840:Microfilament Proteins; C495738:PFN1 protein, human; C495741:PFN2 protein, human; C495739:Pfn1 protein, mouse; C495742:Pfn2 protein, mouse; D051304:Profilins