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  • Neiman, DanielHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel. (author)

Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-07-23
  • American Society for Clinical Investigation,2020
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-423036
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-423036URI
  • https://doi.org/10.1172/jci.insight.136579DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Wos title: Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic beta cells
  • It has been proposed that unmethylated insulin promoter fragments in plasma derive exclusively from β cells, reflect their recent demise, and can be used to assess β cell damage in type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a β cell–specific DNA methylation signature, by simultaneous assessment of 6 DNA methylation markers, that identifies β cell DNA in mixtures containing as little as 0.03% β cell DNA (less than 1 β cell genome equivalent). Based on this assay, plasma from nondiabetic individuals (N = 218, aged 4–78 years) contained on average only 1 β cell genome equivalent/mL. As expected, cell-free DNA (cfDNA) from β cells was significantly elevated in islet transplant recipients shortly after transplantation. We also detected β cell cfDNA in a patient with KATP congenital hyperinsulinism, in which substantial β cell turnover is thought to occur. Strikingly, in contrast to previous reports, we observed no elevation of β cell–derived cfDNA in autoantibody-positive subjects at risk for type 1 diabetes (N = 32), individuals with recent-onset type 1 diabetes (<4 months, N = 92), or those with long-standing disease (>4 months, N = 38). We discuss the utility of sensitive β cell cfDNA analysis and potential explanations for the lack of a β cell cfDNA signal in type 1 diabetes.

Subject headings and genre

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

  • Gillis, DavidHadassah Hebrew Univ, Endocrine Unit, Dept Pediat, Med Ctr, Jerusalem, Israel. (author)
  • Piyanzin, SheinaHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel. (author)
  • Cohen, DanielHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel. (author)
  • Fridlich, OriHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel. (author)
  • Moss, JoshuaHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel. (author)
  • Zick, AviadHadassah Hebrew Univ, Sharett Inst Oncol, Med Ctr, Jerusalem, Israel. (author)
  • Oron, TalSchneider Childrens Med Ctr Israel, Inst Endocrinol & Diabet, Petah Tiqwa, Israel. (author)
  • Sundberg, FridaSahlgrens Univ Hosp, Queen Silvia Childrens Hosp, Gothenburg, Sweden. (author)
  • Forsander, GunSahlgrens Univ Hosp, Queen Silvia Childrens Hosp, Gothenburg, Sweden. (author)
  • Skog, Oskar,Docent, PhD,1981-Uppsala universitet,Klinisk immunologi(Swepub:uu)ossko535 (author)
  • Korsgren, OlleUppsala universitet,Klinisk immunologi(Swepub:uu)ollekors (author)
  • Levy-Khademi, FlorisShaare Zedek Med Ctr, Dept Pediat, Jerusalem, Israel. (author)
  • Arbel, DanHadassah Hebrew Univ, Med Ctr, Pediat Surg, Jerusalem, Israel. (author)
  • Hashavia, SaarHadassah Hebrew Univ, Med Ctr, Pediat Emergency, Jerusalem, Israel. (author)
  • Shapiro, A. M. JamesUniv Alberta, Li Ka Shing Ctr Hlth Res Innovat, Edmonton, AB, Canada. (author)
  • Speake, CateBenaroya Res Inst, Diabet Program, Seattle, WA USA. (author)
  • Greenbaum, CarlaBenaroya Res Inst, Diabet Program, Seattle, WA USA. (author)
  • Hosford, JenniferUniv Florida, Diabet Inst, Dept Pediat, Gainesville, FL 32610 USA.;Univ Florida, Diabet Inst, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. (author)
  • Posgai, AmandaUniv Florida, Coll Med, Gainesville, FL 32610 USA. (author)
  • Atkinson, Mark A.Univ Florida, Diabet Inst, Dept Pediat, Gainesville, FL 32610 USA.;Univ Florida, Diabet Inst, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA.;Univ Florida, Coll Med, Gainesville, FL 32610 USA. (author)
  • Glaser, BenjaminHadassah Hebrew Univ, Dept Internal Med, Endocrinol & Metab Serv, Med Ctr, Jerusalem, Israel. (author)
  • Schatz, Desmond A.Univ Florida, Diabet Inst, Dept Pediat, Gainesville, FL 32610 USA.;Univ Florida, Diabet Inst, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. (author)
  • Shemer, RuthHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel. (author)
  • Dor, YuvalHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel. (author)
  • Hebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.Hadassah Hebrew Univ, Endocrine Unit, Dept Pediat, Med Ctr, Jerusalem, Israel. (creator_code:org_t)

Related titles

  • In:JCI Insight: American Society for Clinical Investigation5:142379-3708

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