lunes, 23 de marzo de 2015

Characterization of large structural genetic mosaicism in human aut... - PubMed - NCBI

Characterization of large structural genetic mosaicism in human aut... - PubMed - NCBI

Am J Hum Genet. 2015 Mar 5;96(3):487-97. doi: 10.1016/j.ajhg.2015.01.011.

Characterization of large structural genetic mosaicism in human autosomes.

Machiela MJ1Zhou W2Sampson JN1Dean MC3Jacobs KB4Black A1Brinton LA1Chang IS5Chen C6Chen C7Chen K8Cook LS9Crous Bou M10De Vivo I10Doherty J11Friedenreich CM12Gaudet MM13Haiman CA14Hankinson SE15Hartge P1Henderson BE14Hong YC16Hosgood HD 3rd17Hsiung CA18Hu W1Hunter DJ19Jessop L1Kim HN20Kim YH21Kim YT22Klein R23Kraft P7Lan Q1Lin D24Liu J25Le Marchand L26Liang X27Lissowska J28Lu L29Magliocco AM30Matsuo K31Olson SH27Orlow I27Park JY32Pooler L33Prescott J10Rastogi R27Risch HA29Schumacher F14Seow A34,Setiawan VW14Shen H35Sheng X33Shin MH36Shu XO37VanDen Berg D14Wang JC38Wentzensen N1Wong MP39Wu C24Wu T40Wu YL41Xia L33Yang HP1Yang PC42Zheng W43Zhou B44Abnet CC1Albanes D1Aldrich MC45Amos C46Amundadottir LT1Berndt SI1Blot WJ47Bock CH48,Bracci PM49Burdett L2Buring JE50Butler MA51Carreón T51Chatterjee N1Chung CC2Cook MB1Cullen M2Davis FG52Ding T53Duell EJ54Epstein CG1Fan JH55Figueroa JD1Fraumeni JF Jr1Freedman ND1Fuchs CS56Gao YT57Gapstur SM13Patiño-Garcia A58Garcia-Closas M59Gaziano JM60,Giles GG61Gillanders EM62Giovannucci EL63Goldin L1Goldstein AM1Greene MH1Hallmans G64Harris CC65Henriksson R66Holly EA49Hoover RN1Hu N1Hutchinson A2Jenab M67Johansen C68Khaw KT69Koh WP70Kolonel LN26Kooperberg C6Krogh V71Kurtz RC72LaCroix A6Landgren A1Landi MT1Li D73Liao LM1Malats N74McGlynn KA1McNeill LH75McWilliams RR76Melin BS66Mirabello L1Peplonska B77Peters U6Petersen GM78Prokunina-Olsson L1Purdue M1Qiao YL79Rabe KG78Rajaraman P1Real FX80Riboli E81Rodríguez-Santiago B82Rothman N1Ruder AM51,Savage SA1Schwartz AG48Schwartz KL83Sesso HD50Severi G84Silverman DT1Spitz MR85Stevens VL13Stolzenberg-Solomon R1Stram D14Tang ZZ53Taylor PR1Teras LR13Tobias GS1Viswanathan K86Wacholder S1Wang Z2Weinstein SJ1Wheeler W87White E6Wiencke JK88Wolpin BM56Wu X89Wunder JS90Yu K1Zanetti KA62Zeleniuch-Jacquotte A91Ziegler RG1de Andrade M78Barnes KC92Beaty TH86Bierut LJ93Desch KC94Doheny KF95Feenstra B96Ginsburg D97Heit JA98Kang JH99Laurie CA100Li JZ101Lowe WL102Marazita ML103Melbye M104Mirel DB105Murray JC106,Nelson SC100Pasquale LR107Rice K100Wiggs JL108Wise A109Tucker M1Pérez-Jurado LA110Laurie CC100Caporaso NE1Yeager M2Chanock SJ111.


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 combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

[PubMed - in process]

No hay comentarios:

Publicar un comentario