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Multiplexing DNA me...
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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 ...
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2020-07-23
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American Society for Clinical Investigation,2020
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-423036
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-423036URI
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https://doi.org/10.1172/jci.insight.136579DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Wos title: Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic beta cells
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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 ...)
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Gillis, DavidHadassah Hebrew Univ, Endocrine Unit, Dept Pediat, Med Ctr, Jerusalem, Israel.
(author)
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Piyanzin, SheinaHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.
(author)
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Cohen, DanielHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.
(author)
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Fridlich, OriHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.
(author)
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Moss, JoshuaHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.
(author)
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Zick, AviadHadassah Hebrew Univ, Sharett Inst Oncol, Med Ctr, Jerusalem, Israel.
(author)
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Oron, TalSchneider Childrens Med Ctr Israel, Inst Endocrinol & Diabet, Petah Tiqwa, Israel.
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Sundberg, FridaSahlgrens Univ Hosp, Queen Silvia Childrens Hosp, Gothenburg, Sweden.
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Forsander, GunSahlgrens Univ Hosp, Queen Silvia Childrens Hosp, Gothenburg, Sweden.
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Skog, Oskar,Docent, PhD,1981-Uppsala universitet,Klinisk immunologi(Swepub:uu)ossko535
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Korsgren, OlleUppsala universitet,Klinisk immunologi(Swepub:uu)ollekors
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Levy-Khademi, FlorisShaare Zedek Med Ctr, Dept Pediat, Jerusalem, Israel.
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Arbel, DanHadassah Hebrew Univ, Med Ctr, Pediat Surg, Jerusalem, Israel.
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Hashavia, SaarHadassah Hebrew Univ, Med Ctr, Pediat Emergency, Jerusalem, Israel.
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Shapiro, A. M. JamesUniv Alberta, Li Ka Shing Ctr Hlth Res Innovat, Edmonton, AB, Canada.
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Speake, CateBenaroya Res Inst, Diabet Program, Seattle, WA USA.
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Greenbaum, CarlaBenaroya Res Inst, Diabet Program, Seattle, WA USA.
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Hosford, JenniferUniv Florida, Diabet Inst, Dept Pediat, Gainesville, FL 32610 USA.;Univ Florida, Diabet Inst, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA.
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Posgai, AmandaUniv Florida, Coll Med, Gainesville, FL 32610 USA.
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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.
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Glaser, BenjaminHadassah Hebrew Univ, Dept Internal Med, Endocrinol & Metab Serv, Med Ctr, Jerusalem, Israel.
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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)
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Shemer, RuthHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.
(author)
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Dor, YuvalHebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.
(author)
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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.
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In:JCI Insight: American Society for Clinical Investigation5:142379-3708
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Neiman, Daniel
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Gillis, David
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Piyanzin, Sheina
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Cohen, Daniel
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Fridlich, Ori
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Moss, Joshua
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Zick, Aviad
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Oron, Tal
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Sundberg, Frida
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Forsander, Gun
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Skog, Oskar, Doc ...
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Korsgren, Olle
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Levy-Khademi, Fl ...
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Arbel, Dan
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Hashavia, Saar
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Shapiro, A. M. J ...
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Speake, Cate
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Greenbaum, Carla
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Hosford, Jennife ...
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Posgai, Amanda
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Atkinson, Mark A ...
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Glaser, Benjamin
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Schatz, Desmond ...
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Shemer, Ruth
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Dor, Yuval
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