A sequence-ready map of the Usher syndrome type III critical region on chromosome 3q.
Usher syndrome type 3 (USH3; MIM 276902) is an autosomal recessive disorder associated with progressive hearing loss and retinal degeneration. We recently refined the localization of USH3 to a 1-cM genetic interval between markers D3S1299 and D3S3625. We have now constructed a bacterial artificial chromosome contig over the region. Novel polymorphic markers were generated and physically fine-mapped, allowing further narrowing of the critical interval to a 250-kb genomic fragment. Of seven ESTs mapping to the initial critical region, WI-11588 and SHGC-133 represent the human SIAH2 gene, which was excluded as a candidate for USH3 by sequencing and subsequently, by its position. KIAA0001 and D3S3882 derive from the transcript of a putative G-protein-coupled receptor gene that was excluded as a candidate by sequencing of patient DNA. These data provide a basis for the sequencing and final characterization of the USH3 region and isolation of the disease gene.
Joensuu
T
T
Haartman Institute, University of Helsinki, Helsinki, 00014, Finland.
Hämäläinen
R
R
Lehesjoki
A E
AE
de la Chapelle
A
A
Sankila
E M
EM
D002876:Chromosomes, Bacterial; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D020224:Expressed Sequence Tags; D005387:Finland; D005808:Genes, Recessive; D005822:Genetic Vectors; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D012162:Retinal Degeneration / Q000235:genetics*; D013577:Syndrome; D015837:Vestibular Diseases / Q000235:genetics*