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Genome-wide copy number analysis uncovers a new HSCR gene: NRG3
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نویسنده
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tang c.s.-m. ,cheng g. ,so m.-t. ,yip b.h.-k. ,miao x.-p. ,wong e.h.-m. ,ngan e.s.-w. ,lui v.c.-h. ,song y.-q. ,chan d. ,cheung k. ,yuan z.-w. ,lei l. ,chung p.h.-y. ,liu x.-l. ,wong k.k.-y. ,marshall c.r. ,scherer s. ,cherny s.s. ,sham p.-c. ,tam p.k.-h. ,garcia-barceló m.-m.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 5
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چکیده
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Hirschsprung disease (hscr) is a congenital disorder characterized by aganglionosis of the distal intestine. to assess the contribution of copy number variants (cnvs) to hscr,we analysed the data generated from our previous genome-wide association study on hscr patients,whereby we identified nrg1 as a new hscr susceptibility locus. analysis of 129 chinese patients and 331 ethnically matched controls showed that hscr patients have a greater burden of rare cnvs (p = 1.50×10-5),particularly for those encompassing genes (p = 5.00×10-6). our study identified 246 rare-genic cnvs exclusive to patients. among those,we detected a nrg3 deletion (p = 1.64×10-3). subsequent follow-up (96 additional patients and 220 controls) on nrg3 revealed 9 deletions (combined p = 3.36×10-5) and 2 de novo duplications among patients and two deletions among controls. importantly,nrg3 is a paralog of nrg1. stratification of patients by presence/absence of hscr-associated syndromes showed that while syndromic-hscr patients carried significantly longer cnvs than the non-syndromic or controls (p = 1.50×10-5),non-syndromic patients were enriched in cnv number when compared to controls (p = 4.00×10-6) or the syndromic counterpart. our results suggest a role for nrg3 in hscr etiology and provide insights into the relative contribution of structural variants in both syndromic and non-syndromic hscr. this would be the first genome-wide catalog of copy number variants identified in hscr. © 2012 tang et al.
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آدرس
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department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong,china,department of psychiatry,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong,china,department of psychiatry,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong,china,department of epidemiology and biostatistics,school of public health,tongji medical college,huazhong university of science and technology,wuhan, China, department of psychiatry,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong,china,centre for reproduction,development,and growth,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong,china,centre for reproduction,development,and growth,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of biochemistry,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of biochemistry,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of orthopedics and traumatology,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of paediatric surgery,shengjing hospital,china medical university,shenyang, China, department of surgery,shenzhen children's hospital,shenzhen, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong, China, program in genetics and genome biology and the centre for applied genomics,the hospital for sick children,toronto,on, Canada, program in genetics and genome biology and the centre for applied genomics,the hospital for sick children,toronto,on,canada,the mclaughlin centre and the department of molecular genetics,university of toronto,toronto,on, Canada, department of psychiatry,li ka shing faculty of medicine,the university of hong kong,hong kong,china,genome research centre,li ka shing faculty of medicine,the university of hong kong,hong kong,china,state key laboratory of brain and cognitive sciences,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of psychiatry,li ka shing faculty of medicine,the university of hong kong,hong kong,china,centre for reproduction,development,and growth,li ka shing faculty of medicine,the university of hong kong,hong kong,china,genome research centre,li ka shing faculty of medicine,the university of hong kong,hong kong,china,state key laboratory of brain and cognitive sciences,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong, China, department of surgery,li ka shing faculty of medicine,the university of hong kong,hong kong,china,centre for reproduction,development,and growth,li ka shing faculty of medicine,the university of hong kong,hong kong, China
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Authors
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