Fine-mapping of Bardet-Biedl syndrome locus on chromosome 16

Purpose. Bardet-Biedl syndrome (BBS) is a heterogeneous autosomal recessive disorder characterized by RP, obesity, polydactyly, mental retardation, and hypogonadism. The purpose of this study is to fine-map and further define the chromosome 16q13 BBS locus (BBS2). Methods. Short tandem repeat polymorphisms (STRPs) and single strand conformational polymorphisms (SSCPs) were identified in YACs, cosmids, and genes within the BBS2 interval and ordered using both genetic and physical mapping data. The newly identified polymorphisms were genotyped in an inbred Bedouin kindred affected with BBS. Pools of DNA from cosmids in the BBS2 interval were used to trap 3′ terminal exons. Results. The high resolution fine-map of the BBS2 locus facilitated the narrowing of the disease gene locus to a 1.5 Mb region. Over 20 3′ terminal exons were trapped in the disease interval and are being analyzed as candidate genes for BBS. Conclusions. We have narrowed the interval containing the gene causing BBS on chromosome 16 to a 1.5 Mb interval and are analyzing trapped exons as possible candidate genes for BBS. Identification of the gene causing BBS on chromosome 16 could aid in the identification of the other BBS loci and could help in the understanding of RP and polygenic disorders such as obesity and hypertension.