Refined Mapping of the Usher Syndrome Type III Locus on Chromosome 3, Exclusion of Candidate Genes, and Identification of the Putative Mouse Homologous Region

• Published in: Genomics (San Diego, Calif.) Vol. 38; no. 3; pp. 255 - 263
• Main Authors: Joensuu, Tarja, Blanco, Gonzalo, Pakarinen, Leenamaija, Sistonen, Pertti, Kääriäinen, Helena, Brown, Steve, Chapelle, Albert de la, Sankila, Eeva-Marja
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.12.1996; Elsevier
• Subjects: Alleles; Animals; Biological and medical sciences; Chromosome Mapping; Chromosomes, Artificial, Yeast - genetics; Chromosomes, Human, Pair 3 - genetics; Contractile Proteins; Finland - epidemiology; Founder Effect; Haplotypes - genetics; Hearing Loss, Sensorineural - classification; Hearing Loss, Sensorineural - epidemiology; Hearing Loss, Sensorineural - genetics; Humans; Linkage Disequilibrium; Lod Score; Medical sciences; Mice - genetics; Microfilament Proteins - genetics; Ophthalmology; Profilins; Retinitis Pigmentosa - classification; Retinitis Pigmentosa - epidemiology; Retinitis Pigmentosa - genetics; Retinopathies; Sequence Homology; Species Specificity; Syndrome; Vestibular Diseases - classification; Vestibular Diseases - epidemiology; Vestibular Diseases - genetics; Europe; Finland; Genetic mapping; Human; Animal model; Retinopathy; Linkage; Genetic marker; Family study; Rodentia; Nutrition disorder; Chromosome A3; Chromosome 3; Genetic disease; Eye disease; Vertebrata; Mammalia; Contig; Gene; Mouse; Usher syndrome; ENT disease
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1996.0626

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 ancestralUSH3mutation segregates. A multipoint linkage analysis assignedUSH3to a 4-cM region betweenD3S1555and a novel markerD3S3625.By analysis of linkage disequilibrium and historical recombinations in 77USH3chromosomes, the location of the Finnish USH3 mutation could be narrowed to an approximately 1-cM interval between the markersD3S1299andD3S3625.A gene for profilin-2 (PFN2) was mapped in the vicinity and excluded as a candidate for USH3 by sequencing. The putative mouse homolog ofPFN2was mapped to mouse chromosome 3, thus suggesting a localization for the mouse homolog ofUSH3.