【摘要】：目的：通過外顯子組測序技術(shù)(whole exome sequencing, WES)從基因水平尋找導(dǎo)致馬爾尼菲青霉病(Penicilliosis marneffei, PSM)易感的基因位點,從患者基因水平探討PSM發(fā)病機制。同時,探討γ干擾素抗體(Anti-interferon-gamma autoantibody)與不合并HIV感染的PSM的相關(guān)性。方法：本研究收集2013年至2016年期間于廣西醫(yī)科大學(xué)第一附屬醫(yī)院確診PSM的3例患兒及其父母、60例不合并HIV感染的PSM患者、62健康志愿者,收集其外周靜脈血及病史資料。 (1)對3例患兒及其父母的基因組DNA提取、純化,進行全外顯子組測序,通過與人類基因組DNA數(shù)據(jù)庫比對,篩選出SNP (Single nucleotide polymorphism)及Indel (Insertion-deletion)突變位點。通過生物信息學(xué)方法在患兒家系內(nèi)及家系間進行篩選,得到候選基因,與NCBI數(shù)據(jù)庫對比后得到可能導(dǎo)致年幼患兒對PSM的易感基因。(2)采用人γ干擾素抗體檢測試劑盒,對不合并HIV感染的PSM患者及健康志愿者檢測血清γ干擾素抗體,探討成人患者對PSM易感的可能原因。結(jié)果： (1)外顯子組測序平均測序深度為111.66×,質(zhì)量控制指標(biāo)均大于90%,測序錯誤率小于1%,得到72682個SNP位點和6505個Indel位點,通過與已知數(shù)據(jù)庫分析比對、生物信息學(xué)分析、手動篩選后得到DOCK8基因突變可能對年幼起病的PSM患兒易感PSM起重要作用。(2)不合并HIV感染的PSM患者與健康志愿者之間γ干擾素檢測結(jié)果有統(tǒng)計學(xué)差異。結(jié)論：全外顯子組測序技術(shù)可用于尋找PSM的易感基因,DOCKS基因可能與幼年患兒對PSM易感相關(guān),在成人患者中,γ干擾素抗體導(dǎo)致的成人起病免疫缺陷綜合征(Adult-onset immunodeficiency)可能與PSM易感相關(guān)。
[Abstract]:Objective: to explore the gene site of (Penicilliosis marneffei, PSM) susceptibility to penicilliosis marneffei by exon group sequencing technique (whole exome sequencing, WES) at gene level, and to explore the pathogenesis of PSM from the gene level of patients. At the same time, to investigate the correlation between interferon gamma antibody (Anti-interferon-gamma autoantibody) and PSM without HIV infection. Methods: from 2013 to 2016, 3 children with PSM diagnosed in the first affiliated Hospital of Guangxi Medical University and 60 healthy volunteers with PSM without HIV infection were collected and their peripheral venous blood and medical history were collected. The results were as follows: (1) the genomic DNA of 3 children and their parents were extracted, purified and sequenced. The mutation sites of SNP (Single nucleotide polymorphism) and Indel (Insertion-deletion) were screened by comparing with the human genomic DNA database. Candidate genes were obtained by bioinformatics in and between pedigrees, and the susceptibility genes to PSM were obtained by comparing with NCBI database. (2) Human interferon 緯 antibody assay kit was used to detect the susceptibility to PSM in young children. Serum interferon 緯 antibodies were detected in PSM patients without HIV infection and in healthy volunteers to explore the possible causes of susceptibility to PSM in adult patients. Results: (1) the average sequencing depth of exon group was 111.66 脳, the quality control index was more than 90, and the error rate of sequencing was less than 1. 72682 SNP loci and 6 505 Indel loci were obtained. The mutation of DOCK8 gene after manual screening may play an important role in the susceptibility to PSM in young children with PSM. (2) the results of interferon 緯 detection in PSM patients without HIV infection were significantly different from those in healthy volunteers. Conclusion: the whole exon sequence technique can be used to search for the susceptible gene of PSM, docks gene, which may be related to the susceptibility to PSM in young children. In adult patients, the susceptibility to PSM may be associated with the incidence of adult immunodeficiency syndrome (Adult-onset immunodeficiency) caused by interferon 緯 antibody.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R519

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