title: Genomics of Islet (Dys)function and Type 2 Diabetes.
abstract: Pancreatic islet dysfunction and beta cell failure are hallmarks of type 2 diabetes mellitus (T2DM) pathogenesis. In this review, we discuss how genome-wide association studies (GWASs) and recent developments in islet (epi)genome and transcriptome profiling (particularly single cell analyses) are providing novel insights into the genetic, environmental, and cellular contributions to islet (dys)function and T2DM pathogenesis. Moving forward, study designs that interrogate and model genetic variation [e.g., allelic profiling and (epi)genome editing] will be critical to dissect the molecular genetics of T2DM pathogenesis, to build next-generation cellular and animal models, and to develop precision medicine approaches to detect, treat, and prevent islet (dys)function and T2DM.
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Lawlor
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics & Genome Sciences, University of Connecticut, Farmington, CT 06032, USA.
authors.forename: Shubham
authors.initials: S
authors.lastname: Khetan
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA.
authors.forename: Duygu
authors.initials: D
authors.lastname: Ucar
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics & Genome Sciences, University of Connecticut, Farmington, CT 06032, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA. Electronic address: michael.stitzel@jax.org.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Stitzel
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D000072669:Gene Editing; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D059010:Single-Cell Analysis; D059467:Transcriptome / Q000235:genetics*
keywords: Type 2 diabetes (T2D); epigenomics; genomics; pancreatic islets; single cell; transcriptomics