Genome-wide analysis of HNF-4 alpha binding sites in correlation with maturity-onset diabetes of the young

Dátum
2014-06-05T08:30:40Z
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The genome-wide association studies have been stared as one of the most advanced biomedical discovery methods, and ever-since are widely applied for the better understanding of genetic components of various diseases including diabetes. A major limitation of these studies consists in the difficulty to explain the correlation between non-coding Single Nucleotide Polymorphisms (SNPs) and the investigated diseases. Hepatocyte nuclear factor-1 alpha and beta, and -4 (HNF1A, HNF1B, HNF4) mutations have been discovered to be the cause of monogenic diabetes, especially in maturity-onset diabetes of the young (MODY). However little is known about the presence of this disease in association with different motifs of HNF- binding sites. Our aim is to investigate this question on a genomic scale and identify the degree of correlation between HNF binding site variants with MODY. The raw ChIP-seq data of published studies was selected from 5 different sequence repository sites and filtered through a set of criteria before being processed by our analysis pipeline (Endre Barta 13-17. EMBnet. Journal, 2011). Here we present our findings for the HNF-binding sites in the investigated tissues and our identification of SNP-s in the HNF binding sites. Further laboratory experiments are needed to validate the differential binding sites and the impact of the SNP-s on the binding of HNF proteins to their targets.

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HNF-4, diabetes
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