Identification of a novel Bardet-Biedl syndrome protein, BBS7, that shares structural features with BBS1 and BBS2

被引:166
作者
Badano, JL
Ansley, SJ
Leitch, CC
Lewis, RA
Lupski, JR
Katsanis, N
机构
[1] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21287 USA
[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[4] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA
[5] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
[6] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
[7] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA
关键词
D O I
10.1086/368204
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder, the primary features of which include obesity, retinal dystrophy, polydactyly, hypogenitalism, learning difficulties, and renal malformations. Conventional linkage and positional cloning have led to the mapping of six BBS loci in the human genome, four of which (BBS1, BBS2, BBS4, and BBS6) have been cloned. Despite these advances, the protein sequences of the known BBS genes have provided little or no insight into their function. To delineate functionally important regions in BBS2, we performed phylogenetic and genomic studies in which we used the human and zebrafish BBS2 peptide sequences to search dbEST and the translation of the draft human genome. We identified two novel genes that we initially named "BBS2L1" and "BBS2L2" and that exhibit modest similarity with two discrete, overlapping regions of BBS2. In the present study, we demonstrate that BBS2L1 mutations cause BBS, thereby defining a novel locus for this syndrome, BBS7, whereas BBS2L2 has been shown independently to be BBS1. The motif-based identification of a novel BBS locus has enabled us to define a potential functional domain that is present in three of the five known BBS proteins and, therefore, is likely to be important in the pathogenesis of this complex syndrome.
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页码:650 / 658
页数:9
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