DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype.

Scientific Reports
Sharon A McGrath-MorrowBenjamin D Singer

Abstract

People with ataxia-telangiectasia (A-T) display phenotypic variability with regard to progression of immunodeficiency, sino-pulmonary disease, and neurologic decline. To determine the association between differential gene expression, epigenetic state, and phenotypic variation among people with A-T, we performed transcriptional and genome-wide DNA methylation profiling in patients with mild and classic A-T progression as well as healthy controls. RNA and genomic DNA were isolated from peripheral blood mononuclear cells for transcriptional and DNA methylation profiling with RNA-sequencing and modified reduced representation bisulfite sequencing, respectively. We identified 555 genes that were differentially expressed among the control, mild A-T, and classic A-T groups. Genome-wide DNA methylation profiling revealed differential promoter methylation in cis with 146 of these differentially expressed genes. Functional enrichment analysis identified significant enrichment in immune, growth, and apoptotic pathways among the methylation-regulated genes. Regardless of clinical phenotype, all A-T participants exhibited downregulation of critical genes involved in B cell function (PAX5, CD79A, CD22, and FCRL1) and upregulation of several ...Continue Reading

References

Jul 1, 1996·Nature Genetics·J A MetcalfeA M Taylor
Jul 4, 1998·Pediatrics·M D CabanaH M Lederman
Oct 22, 1998·European Journal of Human Genetics : EJHG·K LaakeA L Børresen-Dale
May 9, 2001·International Reviews of Immunology·S L NuttM Busslinger
Aug 25, 2007·The Journal of Clinical Investigation·Diana CozmaAndrei Thomas-Tikhonenko
Aug 21, 2009·Annals of Human Genetics·Luciana ChessaBruno Dallapiccola
May 4, 2010·Nature Biotechnology·Cory Y McLeanGill Bejerano
Jun 12, 2012·Gastroenterology·Cécile NotarnicolaPascal De Santa Barbara
Feb 8, 2013·Journal of Pediatric Hematology/oncology·Shizuka MachidaMasatoshi Takagi
Apr 10, 2013·The Journal of Allergy and Clinical Immunology·Gertjan J DriessenMirjam van der Burg
Mar 13, 2014·Current Cancer Drug Targets·Amanda Lay Pin SeeYoon Pin Lim
May 3, 2014·Journal of Clinical Immunology·Matan KrausRaz Somech
Aug 15, 2014·Current Topics in Microbiology and Immunology·F J LiR S Davis
Oct 8, 2014·British Journal of Cancer·G W Rhyasen, D T Starczynowski
Nov 4, 2015·The Journal of Experimental Medicine·Douglas C PalmerNicholas P Restifo
Nov 20, 2015·International Journal of Radiation Oncology, Biology, Physics·Susan E StanleyMary Armanios
May 18, 2016·Ageing Research Reviews·Yosef Shiloh, Howard M Lederman
Jul 15, 2016·Molecular Cancer Therapeutics·Michael ChoiRazelle Kurzrock
Nov 2, 2016·Archives of Disease in Childhood·Rebecca DevaneyJayesh M Bhatt
Nov 26, 2016·Orphanet Journal of Rare Diseases·Cynthia Rothblum-OviattHoward M Lederman
Apr 25, 2017·Journal of Alzheimer's Disease : JAD·Edward FielderDiana Jurk
Nov 21, 2017·Science Advances·Sadiya S KhanDouglas E Vaughan
Dec 7, 2017·Journal of Human Genetics·Kazuhiro IwamaNaomichi Matsumoto
Feb 8, 2018·Genome Biology·F Alexander WolfFabian J Theis
Mar 28, 2018·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Marcela ChmelarovaVladimir Palicka
May 2, 2018·Human Immunology·Divya Sai Katikaneni, Lei Jin
May 10, 2018·Allergologia et immunopathologia·C T M PereiraB T Costa-Carvalho
May 29, 2018·Mutation Research. Reviews in Mutation Research·Martina MagniLaura Zannini
Jun 6, 2018·The Journal of Biological Chemistry·Sharon A McGrath-MorrowBenjamin D Singer
Sep 1, 2018·Translational Research : the Journal of Laboratory and Clinical Medicine·Luisa Morales-NebredaBenjamin D Singer
Sep 7, 2018·JCI Insight·James M WalterBenjamin D Singer
Sep 9, 2018·Anticancer Research·Nicolas LeblancGilles A Robichaud
Nov 9, 2018·Frontiers in Immunology·Jana HundertmarkFrank Tacke
Nov 13, 2018·Science Advances·Lu WangAli Shilatifard
Jan 16, 2019·Nature Genetics·Zhaohui GuCharles G Mullighan
Jan 20, 2019·Journal of Hepatology·Bin GaoHidekazu Tsukamoto
Jan 28, 2019·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Parisa AmirifarAsghar Aghamohammadi
Feb 18, 2019·European Journal of Medical Genetics·Evgeny SuspitsinEvgeny Imyanitov
Mar 2, 2019·Journal of Medical Genetics·Nienke J H van OsMichèl A A P Willemsen
May 3, 2019·Human Mutation·Alice FiévetMarc-Henri Stern
Jul 3, 2019·American Journal of Respiratory Cell and Molecular Biology·Benjamin D Singer

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Citations

Sep 9, 2020·The Journal of Clinical Investigation·Kathryn A HelminBenjamin D Singer
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Venturina StagniDaniela Barilà
Jul 6, 2021·Neurogenetics·Magdalena Krygier, Maria Mazurkiewicz-Bełdzińska

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Methods Mentioned

BETA
methylation profiling
RNA-seq
methylation
PCA

Software Mentioned

Morpheus
RStudio
AutoGeneS
Tophat
SeqMonk
R
prcomp
Bioconductor
mRRBS
Analytics

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