title: Non-coding genome functions in diabetes.
abstract: Most of the genetic variation associated with diabetes, through genome-wide association studies, does not reside in protein-coding regions, making the identification of functional variants and their eventual translation to the clinic challenging. In recent years, high-throughput sequencing-based methods have enabled genome-scale high-resolution epigenomic profiling in a variety of human tissues, allowing the exploration of the human genome outside of the well-studied coding regions. These experiments unmasked tens of thousands of regulatory elements across several cell types, including diabetes-relevant tissues, providing new insights into their mechanisms of gene regulation. Regulatory landscapes are highly dynamic and cell-type specific and, being sensitive to DNA sequence variation, can vary with individual genomes. The scientific community is now in place to exploit the regulatory maps of tissues central to diabetes etiology, such as pancreatic progenitors and adult islets. This giant leap forward in the understanding of pancreatic gene regulation is revolutionizing our capacity to discriminate between functional and non-functional non-coding variants, opening opportunities to uncover regulatory links between sequence variation and diabetes susceptibility. In this review, we focus on the non-coding regulatory landscape of the pancreatic endocrine cells and provide an overview of the recent developments in this field.
authors.affiliation: Department of MedicineImperial College London, London W12 0NN, UKDivision of EndocrinologyGermans Trias i Pujol University Hospital and Research Institute, 08916 Badalona, SpainJosep Carreras Leukaemia Research Institute08916 Badalona, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)08036 Barcelona, Spain.
authors.forename: Inês
authors.initials: I
authors.lastname: Cebola
authors.affiliation: Department of MedicineImperial College London, London W12 0NN, UKDivision of EndocrinologyGermans Trias i Pujol University Hospital and Research Institute, 08916 Badalona, SpainJosep Carreras Leukaemia Research Institute08916 Badalona, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)08036 Barcelona, Spain Department of MedicineImperial College London, London W12 0NN, UKDivision of EndocrinologyGermans Trias i Pujol University Hospital and Research Institute, 08916 Badalona, SpainJosep Carreras Leukaemia Research Institute08916 Badalona, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)08036 Barcelona, Spain Department of MedicineImperial College London, London W12 0NN, UKDivision of EndocrinologyGermans Trias i Pujol University Hospital and Research Institute, 08916 Badalona, SpainJosep Carreras Leukaemia Research Institute08916 Badalona, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)08036 Barcelona, Spain lpasquali@igtp.cat.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pasquali
mesh_terms: D000818:Animals; D021901:DNA, Intergenic / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D021901:DNA, Intergenic
keywords: diabetes (all); diabetes II; gene regulation; islet cells; pancreatic β cell