A large-scale study of SNPs in regulatory elements of

The synthesis of a protein in eukaryotic organisms involves the transcription of a molecule of DNA to RNA (pre-mRNA), the excision of introns and fusion of exons by a process named splicing (yielding the mature mRNA molecule) and finally the translation of mRNA to protein. Not all exons of a gene are necessarily included in a mRNA, generating different isoforms of a protein, a phenomenon named alternative splicing. As a result, the mature mRNA may contain different combinations of exons, longer or shorter exons and even incorporate intronic sequences. The recognition of splice sites (exon-intron borders) involves i-specific sequences in the mRNA known as exonic or intronic splicing enhancers/silencers and iimany protein and ribonucleoprotein factors that recognize the sequences described in (i). Mutations that alter regulatory elements in the mRNA (i), thus interfering in the recognition by the factors described in (ii) may significantly alter the inclusion of a given exon [1]. It is known that mutations in a single nucleotide in specific positions of regulatory elements can interfere in the splicing of exons regulated by such sequences [2]. A common form of variation between two genomes of the same organism is the single nucleotide polimorfisms (SNPs) [3]. There are many studies that correlate SNPs to human diseases, since a single nucleotide change may radically affect the biochemical properties of a protein and may change its expression patterns. Our aim is to perform a large scale analysis of the occurrence of human SNPs in regulatory elements of alternative splicing, using a transcriptome database available in our lab. The database allows one to verify the frequency of SNPs in exons, introns and regulatory elements and make correlation with transcripts. OMIM [4] wi..