Characterization of large structural genetic mosaicism in human autosomes

American Journal of Human Genetics
Mitchell J MachielaStephen J Chanock

Abstract

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large com...Continue Reading

Citations

Oct 4, 2017·Human Molecular Genetics·Mitchell J MachielaStephen J Chanock
Jul 7, 2018·Human Mutation·Klaasjan G OuwensDorret I Boomsma
Jun 14, 2016·Nature Communications·Mitchell J MachielaStephen J Chanock
Nov 24, 2018·Science·Stephen J Chanock
Dec 27, 2018·Current Opinion in Oncology·Mitchell J Machiela
Aug 25, 2017·Nature Reviews. Cancer·Megan E McNerneyMichelle M Le Beau
Nov 22, 2019·Nature·Deborah J ThompsonJohn R B Perry
Jun 5, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Krinio GiannikouDavid J Kwiatkowski
Jul 15, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Víctor Martínez-GlezPablo Lapunzina
Feb 18, 2017·British Journal of Haematology·Talia Wegman-Ostrosky, Sharon A Savage
Sep 1, 2017·Genome Research·Daniel A KingUNKNOWN Deciphering Developmental Disorders Study
Aug 19, 2018·Scientific Reports·Erikka LoftfieldMitchell J Machiela
Mar 10, 2019·Journal of Human Genetics·Mitchell J MachielaStephen J Chanock
Mar 10, 2017·Journal of Human Genetics·Mitchell J MachielaDouglas R Stewart
Jan 4, 2018·Blood Advances·Judith Reina-CastillónJordi Surrallés
Jan 4, 2018·Blood Advances·Mitchell J MachielaStephen J Chanock
Oct 24, 2018·International Journal of Cancer. Journal International Du Cancer·Keyvan TorabiJordi Camps
Jan 23, 2020·Familial Cancer·S AmicoD G Evans
Jun 26, 2020·Nature·Chikashi TeraoYoichiro Kamatani
Apr 12, 2016·Nature Genetics·Weiyin ZhouStephen J Chanock
Jun 3, 2017·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Kathleen E Fischer, Nicole C Riddle
Feb 6, 2020·Human Genetics·Xihan GuoXu Wang
Jan 15, 2016·Journal of Human Genetics·Mitchell J MachielaStephen J Chanock
Dec 19, 2015·Nature Reviews. Cancer·Luis C FernándezFrancisco X Real
Apr 21, 2016·European Journal of Human Genetics : EJHG·Kristina Magaard KoldbyLene Christiansen
Aug 4, 2018·Frontiers in Public Health·Lorna H McNeillDavid W Wetter
Dec 6, 2018·Nature Genetics·Weiyin ZhouStephen J Chanock
Dec 13, 2016·Nature Reviews. Genetics·Lars A ForsbergJan P Dumanski
Sep 12, 2020·Annual Review of Genetics·Jeremy ThorpeJonathan Pevsner
Jan 15, 2021·Scientific Reports·Weiyin ZhouMitchell J Machiela
Jun 24, 2020·American Journal of Human Genetics·Marcus TukeCaroline F Wright
Feb 26, 2021·BMC Genomics·Joseph T GlessnerHakon Hakonarson

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