Abstract:
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In our study, we analysed the colocalisation of exonic SNPs in LAMA2 gene related to the MDC1A form of congenital muscular dystrophy with exonic splicing enhancers (ESEs). Then, we searched the effect of allelic change on ESEs efficacy. The LAMA2 sequence was searched for ESE motifs using the web-based tool ESEfinder. Exons were screened for sequence motifs likely to be recognised by the SR proteins SF2/ASF, SC35, SRp40 and SRp55. Matching sequences are scored and only scores above thresholds are predicted to act as ESEs. Results showed the presence of 2709 ESEs in the 65 coding exons of LAMA2 gene; this number was reduced to 480 significant ESEs after applying the thresholds values filter. Secondly, the analysis of published sequence variations in LAMA2 gene showed the presence of 41 exonic SNPs, 18 of them colocalize with the identified significant ESEs, representing a fraction of about 44%. In addition, the allelic changes in 5 synonymous or non synonymous SNPs can abolish or create an ESE suggesting their potentially functional role in LAMA2 gene expression. These results indicate the utility to consider the functional role of exonic SNPs in splicing and can also answer to many questions about the disease susceptibility and about the phenotypic variability observed in patients sharing with the same mutation in LAMA2 gene.
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