Abstract：
: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.
journal_name
Genome Resjournal_title
Genome researchauthors
Goren A,Kim E,Amit M,Bochner R,Lev-Maor G,Ahituv N,Ast Gdoi
10.1101/gr.6661308subject
Has Abstractpub_date
2008-02-01 00:00:00pages
214-20issue
2eissn
1088-9051issn
1549-5469pii
gr.6661308journal_volume
18pub_type
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