Back to Search
Start Over
Identification of 11 novel mutations in eight BBS genes by high-resolution homozygosity mapping
- Source :
- Journal of Medical Genetics. 47:262-267
- Publication Year :
- 2009
- Publisher :
- BMJ, 2009.
-
Abstract
- Bardet-Biedl syndrome (BBS) is primarily an autosomal recessive disorder characterized by rod-cone dystrophy, obesity, hypogonadism, post-axial polydactyly, renal cysts, and other anomalies of the kidney and urinary tract. To date, mutations in 12 BBS genes as well as in MKS1 and CEP290 have been identified as causing BBS. The vast genetic heterogeneity of BBS renders molecular genetic diagnosis difficult in terms of both the time and cost required to screen all 204 coding exons. Here, we report the use of genome-wide homozygosity mapping as a tool to identify homozygous segments at known BBS loci in BBS individuals from inbred and outbred background. In a worldwide cohort of 45 families, we identified, via direct exon sequencing, causative homozygous mutations in 20 families. Eleven of these mutations were novel, thereby increasing the number of known BBS mutations by 5% (11/218). Thus, in the presence of extreme genetic locus heterogeneity, homozygosity mapping provides a valuable approach to the molecular genetic diagnosis of BBS and will facilitate the discovery of novel pathogenic mutations.
- Subjects :
- Genetics
congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
Genetic heterogeneity
Locus (genetics)
Biology
medicine.disease
Disease gene identification
Gene mapping
Bardet–Biedl syndrome
Genetic linkage
Molecular genetics
medicine
Genetics (clinical)
Exome sequencing
Subjects
Details
- ISSN :
- 14686244 and 00222593
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Genetics
- Accession number :
- edsair.doi...........f99da6ccff6266107641d829792f1d50