Branchio-Oto-Renal Syndrome (BOR) is an autosomal dominant disorder which consists of external, middle and inner ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss and renal anomalies. Variable clinical expression between families suggests that multiple gene loci are involved in causing the disease. Through genetic linkage analysis, the BOR gene has been localized on chromosome 8q. The purpose of the proposed study is to reduce the localization region to 0.5 to l cM and complete a YAC contig in the critical region to identify the BOR gene. The isolation of random human DNA sequences from the YACs will provide a set of closely spaced sequence tagged sites (STSs) which can be used to construct a framework map. This can be used to verify the existing physical map and help to fill the gaps between sets of contiguous clones. Gaps will be filled by walking out from known contiguous segments. Clones will be screened for di-, tri- and tetra- repeat polymorphisms and linkage will be used to refine the position of the BOR gene to the smallest possible region of chromosome 8q. YACs or their derivative cosmid subclones can be used as a resource to identify candidate genes in the region based on their possible association to CpG islands, by displaying evolutionary conserved DNA sequences, or by hybridization to tissue specific cDNA libraries and/or by exon trapping. The BOR gene will be identified among the candidate genes on the basis of its position, tissue specific expression and consistent mutation in affected individuals. Additional families will be required to narrow down the BOR region to the smallest interval. New families will be ascertained and tested for linkage with the markers on chromosome 8q. The possibility of genetic heterogeneity will be explored using the program HOMOG and unlinked families will be put through another round of genome searching to determine the location of new BOR-related genes. Clinical differences between families will be analyzed to determine to what degree they are correlated with different linkage groups. The BOR syndrome results in branchial, auditory, and renal abnormalities in affected individuals and poses serious health problems. Identification of the BOR gene(s) is the first and foremost step to a more comprehensive understanding of the pathogenesis and etiology of this syndrome. Finding the gene(s) will lay the foundation for further research concerning effective treatment and genetic counseling.
| Jaijo, Teresa; Oshima, Aki; Aller, Elena et al. (2012) Mutation screening of the PCDH15 gene in Spanish patients with Usher syndrome type I. Mol Vis 18:1719-26 |
| Malm, Eva; Ponjavic, Vesna; Möller, Claes et al. (2011) Alteration of rod and cone function in children with Usher syndrome. Eur J Ophthalmol 21:30-8 |
| Hmani-Aifa, Mounira; Benzina, Zeineb; Zulfiqar, Fareeha et al. (2009) Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family. Eur J Hum Genet 17:474-82 |
| Tamayo, M L; Lopez, G; Gelvez, N et al. (2008) Genetic counseling in Usher syndrome: linkage and mutational analysis of 10 Colombian families. Genet Couns 19:15-27 |
| Oshima, A; Jaijo, T; Aller, E et al. (2008) Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I. Hum Mutat 29:E37-46 |
| Gopalarao, Deepika; Kimberling, William J; Jesteadt, Walt et al. (2008) Is hearing loss due to mutations in the Connexin 26 gene progressive? Int J Audiol 47:11-20 |
| Cremers, Frans P M; Kimberling, William J; Kulm, Maigi et al. (2007) Development of a genotyping microarray for Usher syndrome. J Med Genet 44:153-60 |
| Yang, Yan-Jun; Wang, Yan-Bo; Lei, Shu-Feng et al. (2007) AHSG gene polymorphisms are associated with bone mineral density in Caucasian nuclear families. Eur J Epidemiol 22:527-32 |
| Chen, Xiang-Ding; Shen, Hui; Recker, Robert R et al. (2006) Linkage exclusion mapping with bone size in 79 Caucasian pedigrees. J Bone Miner Metab 24:337-43 |
| Chen, Xiang-Ding; Shen, Hui; Lei, Shu-Feng et al. (2006) Exclusion mapping of chromosomes 1, 4, 6 and 14 with bone mineral density in 79 Caucasian pedigrees. Bone 38:450-5 |
Showing the most recent 10 out of 105 publications
