RT Journal
A1 Goren, Amir
A1 Kim, Eddo
A1 Amit, Maayan
A1 Bochner, Ron
A1 Lev-Maor, Galit
A1 Ahituv, Nadav
A1 Ast, Gil
T1 Alternative approach to a heavy weight problem
JF Genome Research 
JO Genome Research 
YR 2007 
FD December 01 
VO 18 
IS 2 
SP 000 
OP 000 
DO 10.1101/gr.6661308 
UL http://genome.cshlp.org/content/early/2007/12/01/gr.6661308.abstract 
AB Obesity is reaching epidemic proportions in developed countries and represents a significant risk factor for hypertension, heart disease, diabetes, and dyslipidemia. Splicing mutations constitute at least 14% of disease-causing mutations, thus implicating polymorphisms that affect splicing as likely candidates for disease susceptibility. A recent study suggested that genes associated with obesity were significantly enriched for rare nucleotide variants. Here, we examined these variants and revealed that they are located near splice junctions and tend to affect exonic splicing regulatory sequences. We also show that the majority of the exons that harbor these SNPs are constitutively spliced, yet they exhibit weak splice sites, typical to alternatively spliced exons, and are hence suboptimal for recognition by the splicing machinery and prone to become alternatively spliced. Using ex vivo assays, we tested a few representative variants and show that they indeed affect splicing by causing a shift from a constitutive to an alternative pattern, suggesting a possible link between extreme body mass index and abnormal splicing patterns.