Novel sequence variations in LAMA2 and SGCG genes modulating cis-acting regulatory elements and RNA secondary structure

• Main Authors: Olfa Siala, Ikhlass Hadj Salem, Abdelaziz Tlili, Imen Ammar, Hanen Belguith, Faiza Fakhfakh
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Genética 2010-01-01
• Series: Genetics and Molecular Biology
• Subjects: muscular dystrophies; exon splicing enhancer; RNA fold; SR proteins
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000100032
• ISSN: 1415-4757; 1678-4685

In this study, we detected new sequence variations in LAMA2 and SGCG genes in 5 ethnic populations, and analysed their effect on enhancer composition and mRNA structure. PCR amplification and DNA sequencing were performed and followed by bioinformatics analyses using ESEfinder as well as MFOLD software. We found 3 novel sequence variations in the LAMA2 (c.3174+22_23insAT and c.6085 +12delA) and SGCG (c.*102A/C) genes. These variations were present in 210 tested healthy controls from Tunisian, Moroccan, Algerian, Lebanese and French populations suggesting that they represent novel polymorphisms within LAMA2 and SGCG genes sequences. ESEfinder showed that the c.*102A/C substitution created a new exon splicing enhancer in the 3'UTR of SGCG genes, whereas the c.6085 +12delA deletion was situated in the base pairing region between LAMA2 mRNA and the U1snRNA spliceosomal components. The RNA structure analyses showed that both variations modulated RNA secondary structure. Our results are suggestive of correlations between mRNA folding and the recruitment of spliceosomal components mediating splicing, including SR proteins. The contribution of common sequence variations to mRNA structural and functional diversity will contribute to a better study of gene expression.