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

doi:10.1006/geno.1996.0626

Genomics

Volume 38, Issue 3, 15 December 1996, Pages 255-263

https://doi.org/10.1006/geno.1996.0626 Get rights and content

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 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.

References (0)

Cited by (29)

Founder variations in isolated populations
2020, Genome Plasticity in Health and Disease
Isolated populations, also called population isolates and genetic isolates, present several characteristic features that make them useful in the study of the genetic basis of both Mendelian and complex disorders. The consensus regarding population isolates is that they have been founded by a small number of individuals, followed by a period of genetic isolation and growth. In modern times characterized by widespread mobility of people around the world, few human populations can be considered genetic isolates. In this chapter we outline the reasons for their usefulness in genetic studies and describe the role they have played and continue to play in gene-mapping efforts. Specific examples of gene identification are provided.
Retinitis Pigmentosa and Allied Disorders
2005, Retina: Fourth Edition
Disease associated balanced chromosome rearrangements (DBCR): Report of two new cases
2003, Annales de Genetique
Citation Excerpt :
The proband in case 2 has profound hearing loss and partial blindness, features similar to Usher syndrome type III (USH3, OMIM # 276902) [20,21]. The USH3 locus was mapped to chromosome region 3q25 and the disease gene was recently cloned [22–24]. Though the USH3 gene is mapped proximal to our breakpoint at 3q27, it is noteworthy that our patient did present with the cardinal features of this syndrome.
Disease associated balanced chromosome rearrangements (DBCR) causing truncation, deletion, inactivation or over-expression of specific genes are instrumental in identifying and cloning several disease genes and are estimated to be much more common than anticipated. In one survey, the minimal frequency of combined balanced de novo reciprocal translocations and inversions causing abnormal phenotype is estimated to be 0.17%, a sixfold increase compared to the general population suggesting a causative linkage between the abnormality and the observed phenotypic traits. Here, we report two new cases of apparently balanced de novo translocations resulting in developmental delay and dysmorphic features.
Usher syndrome type III: Revised genomic structure of the USH3 gene and identification of novel mutations
2002, American Journal of Human Genetics
Usher syndrome type III is an autosomal recessive disorder characterized by progressive sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa. The disease gene was localized to 3q25 and recently was identified by positional cloning. In the present study, we have revised the structure of the USH3 gene, including a new translation start site, 5′ untranslated region, and a transcript encoding a 232–amino acid protein. The mature form of the protein is predicted to contain three transmembrane domains and 204 residues. We have found four new disease-causing mutations, including one that appears to be relatively common in the Ashkenazi Jewish population. We have also identified mouse (chromosome 3) and rat (chromosome 2) orthologues, as well as two human paralogues on chromosomes 4 and 10.
Circling, deafness, and yellow coat displayed by yellow submarine (Ysb) and light coat and circling (Lcc) mice with mutations on chromosome 3
2002, Genomics
We describe here two mouse mutants, yellow submarine (Ysb) and light coat and circling (Lcc). Ysb arose as the result of insertions of a transgene, pAA2, into the genome. Lcc is an independent, radiation-induced mutation. Both mutants are characterized by recessive circling behavior and deafness, associated with a non-segregating, semi-dominant yellow coat color. Complementation tests showed that Ysb and Lcc are allelic. We attribute the yellow coat in Ysb and Lcc mice to the absence of black awl overhairs, increased agouti zigzag underhairs, and the presence of agouti awls with long subapical yellow pigment. Chromosomal mapping and genomic characterization showed the Ysb and Lcc mutations involve complex chromosomal rearrangements in overlapping regions of mouse chromosome 3, A2/A3–B/C and B–E1, respectively. Ysb and Lcc show for the first time, to our knowledge, the presence of genes in the B–C region of chromosome 3 important for balance and hearing and the pigmentation and specification of coat hair.
A high-resolution genetic, physical, and comparative gene map of the doublefoot (Dbf) region of mouse chromosome 1 and the region of conserved synteny on human chromosome 2q35
2001, Genomics
The mouse doublefoot (Dbf) mutant exhibits preaxial polydactyly in association with craniofacial defects. This mutation has previously been mapped to mouse chromosome 1. We have used a positional cloning strategy, coupled with a comparative sequencing approach using available human draft sequence, to identify putative candidates for the Dbf gene in the mouse and in homologous human region. We have constructed a high-resolution genetic map of the region, localizing the mutation to a 0. 4-cM (±0.0061) interval on mouse chromosome 1. Furthermore, we have constructed contiguous BAC/PAC clone maps across the mouse and human Dbf region. Using existing markers and additional sequence tagged sites, which we have generated, we have anchored the physical map to the genetic map. Through the comparative sequencing of these clones we have identified 35 genes within this interval, indicating that the region is gene-rich. From this we have identified several genes that are known to be differentially expressed in the developing mid-gestation mouse embryo, some in the developing embryonic limb buds. These genes include those encoding known developmental signaling molecules such as WNT proteins and IHH, and we provide evidence that these genes are candidates for the Dbf mutation.

View all citing articles on Scopus

¹: To whom correspondence should be addressed at Department of Medical Genetics, University of Helsinki, P.O. Box 21 (Haartmaninkatu 3), FIN-00014, Finland. Telephone: +358-9-434 61. Fax: +358-9-434 6677. E-mail: [email protected].

View full text

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

Abstract

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