Genomic alterations in biliary atresia suggest region of potential disease susceptibility in 2q37.3.
Genomic alterations in biliary atresia suggest region of potential disease susceptibility in 2q37.3.
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DOI：
10.1002/ajmg.a.33332
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发表时间：
2010-04
影响因子：
2
通讯作者：
Spinner, Nancy B.
中科院分区：
文献类型：
--
作者：
Leyva-Vega, Melissa;Gerfen, Jennifer;Thiel, Brian D.;Jurkiewicz, Dorota;Rand, Elizabeth B.;Pawlowska, Joanna;Kaminska, Diana;Russo, Pierre;Gai, Xiaowu;Krantz, Ian D.;Kamath, Binita M.;Hakonarson, Hakon;Haber, Barbara A.;Spinner, Nancy B.
胆道闭锁是一种进行性的、原发性的肝外胆道系统闭塞，仅发生于新生儿期。它是导致儿童肝移植的最常见疾病。BA的病因尚不清楚，尽管已提出感染，免疫和遗传原因。虽然BA在家族中的复发并不常见，但有超过30个多重家族报道，并假设潜在的遗传易感性。我们筛选了一组35例BA患者的基因组改变，可能赋予BA的易感性。DNA在Illumina Quad 550平台上进行基因分型，该平台分析了超过550，000个单核苷酸多态性（SNP）的基因组缺失和重复。将拷贝数增加和减少的区域与对照人群中发现的区域进行比较。为了确定可以作为BA易感因素的区域，我们搜索了在BA患者中发现的区域，但在对照组中没有发现。我们确定了两个不相关的BA患者重叠杂合缺失2q37.3。患者1具有1.76 Mb（280 SNP）的杂合缺失，其含有30个基因。患者2具有含有55个基因的5.87 Mb（1，346 SNP）杂合缺失。染色体2q37.3上240，936，900 - 242，692，820的1.76 Mb重叠缺失构成了关键区域，该区域内的基因可能是BA敏感性的候选基因。
Biliary atresia (BA) is a progressive, idiopathic obliteration of the extrahepatic biliary system occurring exclusively in the neonatal period. It is the most common disease leading to liver transplantation in children. The etiology of BA is unknown, although infectious, immune and genetic causes have been suggested. While the recurrence of BA in families is not common, there are more than 30 multiplex families reported and an underlying genetic susceptibility has been hypothesized. We screened a cohort of 35 BA patients for genomic alterations that might confer susceptibility to BA. DNA was genotyped on the Illumina Quad550 platform, which analyzes over 550,000 single nucleotide polymorphisms (SNPs) for genomic deletions and duplications. Areas of increased and decreased copy number were compared to those found in control populations. In order to identify regions that could serve as susceptibility factors for BA, we searched for regions that were found in BA patients, but not in controls. We identified two unrelated BA patients with overlapping heterozygous deletions of 2q37.3. Patient 1 had a 1.76 Mb (280 SNP), heterozygous deletion containing thirty genes. Patient 2 had a 5.87 Mb (1,346 SNP) heterozygous deletion containing fifty-five genes. The overlapping 1.76 Mb deletion on chromosome 2q37.3 from 240,936,900 to 242,692,820 constitutes the critical region and the genes within this region could be candidates for susceptibility to BA.
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影响因子：
30.8
作者：
Kugathasan, Subra;Baldassano, Robert N.;Bradfield, Jonathan P.;Sleiman, Patrick M. A.;Imielinski, Marcin;Guthery, Stephen L.;Cucchiara, Salvatore;Kim, Cecilia E.;Frackelton, Edward C.;Annaiah, Kiran;Glessner, Joseph T.;Santa, Erin;Willson, Tara;Eckert, Andrew W.;Bonkowski, Erin;Shaner, Julie L.;Smith, Ryan M.;Otieno, F. George;Peterson, Nicholas;Abrams, Debra J.;Chiavacci, Rosetta M.;Grundmeier, Robert;Mamula, Petar;Tomer, Gitit;Piccoli, David A.;Monos, Dimitri S.;Annese, Vito;Denson, Lee A.;Grant, Struan F. A.;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
DOI：
10.1002/ajmg.1320430317
发表时间：
1992-06-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
GUNASEKARAN, TS;HASSALL, EG;YONG, SL
通讯作者：
YONG, SL
影响因子：
158.5
作者：
Maris, John M.;Mosse, Yael P.;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
影响因子：
1.1
作者：
HARPER, P;PLANT, JW;UNGER, DB
通讯作者：
UNGER, DB
影响因子：
30.8
作者：
Birnbaum, Stefanie;Ludwig, Kerstin U.;Mangold, Elisabeth
通讯作者：
Mangold, Elisabeth