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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bardet-Biedl syndrome (BBS) is a pleiotropic genetic disorder with the cardinal features of obesity, photoreceptor degeneration, polydactyly, hypogenitalism, renal abnormalities, and developmental delay. Other associated clinical findings in BBS patients include diabetes, hypertension, and congenital heart defects. The clinical diagnosis is based on the presence of at least four of the cardinal symptoms. BBS is recognized to be a genetically heterogeneous autosomal recessive disorder mapping to eight known loci. Positional cloning and candidate gene evaluation have resulted in the identification of six BBS genes. Mutation of one of these genes, BBS6, also causes McKusick-Kaufman syndrome. The BBS6 gene is predicted to code for a protein with sequence similarity to the chaperonin family of proteins. The predicted BBS1, BBS2, BBS4, BBS7, and BBS8 gene products do not seem to be molecular chaperones, on the basis of a lack of sequence similarity to the chaperonin family of proteins. The identification of BBS8 suggests a possible role in cilia function for BBS gene products. It remains to be determined whether the multiple BBS proteins are part of a multisubunit complex or do not directly interact with each other but are part of a common pathway. The study of BBS illustrates the value of using isolated inbred populations for the study of human genetic diseases and suggests strategies for facilitating the study of complex diseases and traits.
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PMID:Use of isolated populations in the study of a human obesity syndrome, the Bardet-Biedl syndrome. 1515 61

The pleiotropic features of obesity, retinal degeneration, polydactyly, kidney abnormalities, cognitive impairment, hypertension, and diabetes found in Bardet-Biedl syndrome (BBS) make this disorder an important model disorder for identifying molecular mechanisms involved in common human diseases. To date, 16 BBS genes have been reported, seven of which (BBS1, 2, 4, 5, 7, 8, and 9) code for proteins that form a complex known as the BBSome. The function of the BBSome involves ciliary membrane biogenesis. Three additional BBS genes (BBS6, BBS10, and BBS12) have homology to type II chaperonins and interact with CCT/TRiC proteins and BBS7 to form a complex termed the BBS-chaperonin complex. This complex is required for BBSome assembly. Little is known about the process and the regulation of BBSome formation. We utilized point mutations and null alleles of BBS proteins to disrupt assembly of the BBSome leading to the accumulation of BBSome assembly intermediates. By characterizing BBSome assembly intermediates, we show that the BBS-chaperonin complex plays a role in BBS7 stability. BBS7 interacts with BBS2 and becomes part of a BBS7-BBS2-BBS9 assembly intermediate referred to as the BBSome core complex because it forms the core of the BBSome. BBS1, BBS5, BBS8, and finally BBS4 are added to the BBSome core to form the complete BBSome.
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PMID:Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome. 2250 27