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  • Fadista, JoaoLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups (author)

Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism.

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-09-08
  • Proceedings of the National Academy of Sciences,2014

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:450b0429-fa4a-47c5-8ada-05d3121e122e
  • https://lup.lub.lu.se/record/4691998URI
  • https://doi.org/10.1073/pnas.1402665111DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion. In addition, we provide a genome-wide catalog of allelic expression imbalance, which is also enriched in known T2D-associated loci. Notably, allelic imbalance in paternally expressed gene 3 (PEG3) was associated with its promoter methylation and T2D status. Finally, RNA editing events were less common in islets than previously suggested in other tissues. Taken together, this study provides new insights into the complexity of gene regulation in human pancreatic islets and better understanding of how genetic variation can influence glucose metabolism.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Vikman, PetterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)wbl-pwi (author)
  • Ottosson Laakso, EmiliaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-eo_ (author)
  • Mollet, InesLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups(Swepub:lu)med-imo (author)
  • Esguerra, JonathanLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups(Swepub:lu)med-jer (author)
  • Taneera, JalalLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Diabetes - öpatofysiologi,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Diabetes - Islet Patophysiology(Swepub:lu)stem-jta (author)
  • Storm, PetterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-psm (author)
  • Osmark, PeterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)medk-pos (author)
  • Ladenvall, ClaesLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-cll (author)
  • Prasad, RashmiLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-rpa (author)
  • Hansson, Karin BLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-knh (author)
  • Finotello, Francesca (author)
  • Uvebrant, Kristina (author)
  • Ofori, JonesLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups(Swepub:lu)med-joi (author)
  • Di Camillo, Barbara (author)
  • Krus, UlrikaLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)medk-ufr (author)
  • Cilio, CorradoLund University,Lunds universitet,Diabetes - immunovirologi,Forskargrupper vid Lunds universitet,Diabetes - Immunovirology,Lund University Research Groups(Swepub:lu)endo-cci (author)
  • Hansson, OlaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)medk-oha (author)
  • Eliasson, LenaLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups(Swepub:lu)mphy-lel (author)
  • Rosengren, AndersLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)mphy-aro (author)
  • Renström, ErikLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)mphy-ere (author)
  • Wollheim, ClaesLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-cwe (author)
  • Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-lgr (author)
  • Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences111:38, s. 13924-139291091-64900027-8424

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