發(fā)布時(shí)間：2018-05-17 08:31

  本文選題：先天性巨結(jié)腸 + 單核苷酸�。� 參考：《華中科技大學(xué)》2012年博士論文

【摘要】：目的采用新一代測序技術(shù)對一個(gè)漢族巨結(jié)腸家系中2例患者進(jìn)行全外顯子測序，測序數(shù)據(jù)進(jìn)行多步驟過濾分析，初步篩選先天性巨結(jié)腸的易感基因。 方法收集一個(gè)先天性巨結(jié)腸家系中母子2個(gè)患者的靜脈血采用全外顯子捕獲和新一代測序技術(shù)進(jìn)行高通量測序，測序結(jié)果與人類HAPMAP8，dbSNP130和1000Genome Project數(shù)據(jù)庫進(jìn)行比對過濾已報(bào)道的常見變異，再過濾掉同義突變，將母子單核苷酸非同義突變進(jìn)行整合，并通過Sanger法測序排除外顯子測序的假陽性結(jié)果，初步篩選出候選基因。 結(jié)果測序結(jié)果通過原始質(zhì)量評分過濾，母子兩個(gè)患者共得到8.4G的數(shù)據(jù)。過濾掉不在外顯子區(qū)域的單核苷酸變化(SNVs)，落在外顯子區(qū)域的單核苷酸變化數(shù)目母親為13948個(gè)，，兒子為13856個(gè)；過濾掉公共數(shù)據(jù)庫（HAPMAP8，dbSNP130和1000Genome Project）的常見變異，落在外顯子區(qū)域的未報(bào)道的單核苷酸變化數(shù)目母親為3472個(gè)，兒子為3345個(gè)；過濾掉同義突變，非同義突變的單核苷酸變化數(shù)目母親為470個(gè)，兒子為458個(gè)；整合母子兩個(gè)共有的非同義突變數(shù)目篩選出17個(gè)基因。Sanger法排除外顯子測序C22orf42(G＞A)假陽性結(jié)果，最后得到16個(gè)候選基因。 結(jié)論NRG3；LAMA3；BRIP1；JARID2； KRT6A；LEPREL1；OR8J3；PLA2G4C；PRBP4；RNF10；SPRY1；TMPRSS11E；VARS2；NBPF16；GSTM4；PRSS116個(gè)基因可能為巨結(jié)腸的易感基因，但須進(jìn)一步確認(rèn)。
[Abstract]:Objective to detect the susceptibility genes of Hirschsprung's colon (Hirschsprung's disease) by sequencing two patients with Hirschsprung's disease (Hirschsprung's disease) in a Han Chinese pedigree by multistep filtration analysis. Methods the venous blood of two patients with Hirschsprung's disease was collected from a family of Hirschsprung's disease and high throughput sequencing was performed by whole exon capture and a new generation of sequencing techniques. The sequencing results were compared with human HAPMAP8dbSNP130 and 1000Genome Project database to filter the reported common mutations, then filter out synonymous mutations, integrate mother and son single nucleotide nonsynonymous mutations, and exclude the false positive results of exon sequencing by Sanger sequencing. Candidate genes were preliminarily screened. Results the sequencing results were filtered by the original quality score, and the data of the two patients were 8.4G. The number of single nucleotide variations in the exon region was 13948 for mothers and 13,856 for sons, and the common variations in the common database, HAPMAP8dbSNP130 and 1000Genome projects, were filtered out. The number of unreported single nucleotide changes in the exon region was 3472 for mother and 3345 for son, 470 for mother and 458 for son, filtering out synonymous mutation and non-synonymous mutation. 17 genes were screened by Sanger method to exclude exon sequencing C22orf42(G > A) false positive results were obtained. Finally, 16 candidate genes were obtained. Conclusion NRG3, Lama 3, BRIP1, JARID2, KRT6A, LEPREL1, OR8J3G4G4, PRBP4, RNF10, SPRY1, TMPRSS11EVARS2, NBPF16GSTM4PRSS116, may be the susceptibility genes of megacolon, but need to be further confirmed.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R722.11

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相關(guān)期刊論文 前2條

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2 辜清泉;楊琳;楊旭;;外顯子測序技術(shù)在疾病研究中的應(yīng)用[J];分子診斷與治療雜志;2011年05期

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