From single nucleotide polymorphism to transcriptional mechanism: a model for FRMD3 in diabetic nephropathy.
Diabetes
; 62(7): 2605-12, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23434934
ABSTRACT
Genome-wide association studies have proven to be highly effective at defining relationships between single nucleotide polymorphisms (SNPs) and clinical phenotypes in complex diseases. Establishing a mechanistic link between a noncoding SNP and the clinical outcome is a significant hurdle in translating associations into biological insight. We demonstrate an approach to assess the functional context of a diabetic nephropathy (DN)-associated SNP located in the promoter region of the gene FRMD3. The approach integrates pathway analyses with transcriptional regulatory pattern-based promoter modeling and allows the identification of a transcriptional framework affected by the DN-associated SNP in the FRMD3 promoter. This framework provides a testable hypothesis for mechanisms of genomic variation and transcriptional regulation in the context of DN. Our model proposes a possible transcriptional link through which the polymorphism in the FRMD3 promoter could influence transcriptional regulation within the bone morphogenetic protein (BMP)-signaling pathway. These findings provide the rationale to interrogate the biological link between FRMD3 and the BMP pathway and serve as an example of functional genomics-based hypothesis generation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
/
Proteínas Supressoras de Tumor
/
Nefropatias Diabéticas
/
Modelos Genéticos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos