本文關鍵詞： HLA-DPB1 四川漢族 測序 高分辨分型 禁忌錯配　出處：《北京協(xié)和醫(yī)學院》2015年碩士論文　論文類型：學位論文

【摘要】：[目的]調查四川骨髓庫漢族人群HLA-DPB1等位基因多態(tài)性分布情況,估計四川骨髓庫漢族人群非血緣造血干細胞移植中可能存在的HLA-DPB1錯配情況及錯配模式,同時分析HLA-A,-B,-DRB1全相合的同胞間HLA-DPB1位點存在的錯配情況及錯配模式。[方法]從四川骨髓庫隨機抽取1097份四川漢族非血緣造血干細胞移植捐獻者DNA樣本,從四川省臍帶血造血干細胞庫和重慶市血液中心臨床移植配型供受者家系中篩選同胞間HLA-A,-B,-DRB1全相合的移植家系901個。采用PCR-SBT技術對DNA樣本進行HLA-DPB1測序分型。經(jīng)ABI 3730測序儀測序,用UTYPE6.0軟件分析結果。對于因第二外顯子區(qū)域內的Trans/cis連鎖產(chǎn)生的模棱兩可結果,設計組特異性測序引物(Group Specific Sequencing Primers, GSSPs)進行單等位基因測序。對于區(qū)別在第二外顯子外的模棱兩可結果,以G為后綴表G組,指定分型結果。用直接計數(shù)法統(tǒng)計四川骨髓庫漢族人群中HLA-DPB1等位基因的基因頻率；用SPSS19.0軟件對不同人群HLA-DPB1等位基因分布進行X2檢驗。采用T細胞表位(T-cell-epitope, TCE) 3/4模型理論推測四川漢族非血緣造血干細胞移植供受者之間及HLA-A,-B,-DRB1全相合的同胞之間可能存在的HLA-DPB1等位基因錯配模式。[結果](1)在四川骨髓庫漢族人群中共檢出35種HLA-DPB1等位基因型別,較常見的等位基因及其頻率分別是：HLA-DPB1*05:01:01G(gene frequency, GF=40.9%)、*02:01:02G(GF=16.1%)、*02:02(GF=8.4%)、* 13:01:01G(GF=7.9%)、*04：01：01G(GF=6.8%)等,這5種等位基因共占80.1%。35種等位基因中檢出9種美國組織相容性和免疫遺傳學協(xié)會(American Society for Histocompatibility and Immunogenetics, ASHI)常見及確認等位基因(Common and Well-Documented, CWD)表中尚不包含的等位基因,分別是：DPB1*41：01：01(5例),DPB1*48：01(3例),DPB1*100：01(3例),DPB1*04:01:15、DPB1*25:01、DPB1*71:01、DPB1*91:01、DPB1*93：01和DPB1*331：01各1例。還有2例新等位基因,世界衛(wèi)生組織命名委員會將其分別命名為DPB1*363：01和DPB1*394：01。四川骨髓庫漢族人群與廣州漢族人群HLA-DPB1等位基因分布之間的差異不具有統(tǒng)計學意義(X2=21.556,P0.01),而與山東漢族(X2=51.134,P0.01)及高加索人群(X2=712.92,P0.01)之間的差異均具有統(tǒng)計學意義。(2)按照TCE模型對四川骨髓庫漢族人群HLA-DPB1等位基因進行分組,高免疫原性組占2.19%,中等免疫原性組占8.89%,低免疫原性組占88.92%。四川漢族人群中進行非血緣造血干細胞移植時,根據(jù)TCE模型推測HLA-DPB1可能存在的允許錯配占34.28%,在GvH方向和HvG方向的禁忌錯配分別為17.27%,TCE3模型允許而TCE4模型不允許的錯配在GJvH方向和HvG方向分別為15.59%。(3)移植家系研究中發(fā)現(xiàn)DPB1位點交換率為5.2%。允許錯配占交換家系53%；另外47%為禁忌錯配。]HLA-DPB1禁忌錯配在HLA-A,-B,-DRB1全相合的同胞中占2.44%。[結論]四川骨髓庫漢族人群中HLA-DPB1高頻等位基因分布集中,多態(tài)性較強,并具有自身的分布特點。根據(jù)TCE模型分析表明,在四川漢族非血緣造血干細胞移植時可能存在HLA-DPB1的禁忌錯配,提示臨床需要對此重視。根據(jù)TCE模型分析發(fā)現(xiàn),在HLA-A,-B,-DRB1全相合的同胞間可能存在HLA-DPB1的交換,在進行同胞間造血干細胞移植時,也可能存在HLA-DPB1的禁忌錯配。
[Abstract]:Objective: To investigate the Sichuan bone marrow bank Han population HLA-DPB1 gene polymorphism distribution of Sichuan Han population estimate bone marrow unrelated hematopoietic stem and mismatch HLA-DPB1 mismatch patterns may exist in the cell transplantation, and the analysis of the HLA-A, -B, -DRB1 identical sibling mismatch and HLA-DPB1 loci are wrong distribution mode. Methods from Sichuan marrow library on a random sample of 1097 Sichuan Han unrelated hematopoietic stem cell donor DNA samples from Sichuan Province, umbilical cord blood stem cell bank and Chongqing Blood Center for clinical transplantation typing by HLA-A screening, sibling incidencein family -B, -DRB1 matched transplantation in 901 families a sample of DNA. HLA-DPB1 genotyping using PCR-SBT technology. The ABI 3730 sequencing, the results were analyzed with UTYPE6.0 software. As a result of the second exon region of the Trans/cis chain from the two edge Can the design of group specific primers (Group Specific Sequencing Primers, GSSPs) by single allele sequencing. Results for the difference in the ready to accept either course of exon 2 of G group with the G suffix table, specify the typing results. The gene frequency of HLA-DPB1 by direct counting statistics of Sichuan marrow Library in Han population gene; X2 test was performed on different populations of HLA-DPB1 alleles with SPSS19.0 software. The T cell epitopes (T-cell-epitope, TCE) 3/4 model theory between Sichuan Han unrelated hematopoietic stem cell transplantation by HLA-A and -B, may exist between -DRB1 identical sibling HLA-DPB1 allele. With the model. Results (1) in Sichuan Han population were detected in the bone marrow of 35 type of HLA-DPB1 allele, common alleles and their frequencies are: HLA-DPB1*05:01:01G (gene frequency, GF= 40.9%), *02:01:02G (GF=16.1%), *02:02 (GF=8.4%), * 13:01:01G (GF=7.9%), *04:01:01G (GF=6.8%), a total of 5 alleles of 9 American histocompatibility and immunogenetics association detection 80.1%.35 allele (American Society for Histocompatibility and Immunogenetics, ASHI) and common confirmation a gene (Common and Well-Documented, CWD) in the table is not contained in the alleles were DPB1*41:01:01 (5 cases), DPB1*48:01 (3 cases), DPB1*100:01 (3 cases), DPB1*04:01:15, DPB1, *25:01, DPB1*71:01, DPB1*91:01, DPB1*93:01 and DPB1*331:01 of the 1 cases. There were 2 new alleles. The committee will be named WHO named as the difference between the distribution of DPB1*363:01 and DPB1*394:01. in Sichuan Han population of bone marrow and HLA-DPB1 in Guangzhou Han population allele was not statistically significant (X2=21.556 P0.01, and Shandong), Han (X2=51.134, P0.01) and Caucasian (X2=712.92, P0.01) between the differences were statistically significant. (2) according to the TCE model of Sichuan marrow library Han population allele HLA-DPB1 group, high immunogenicity group accounted for 2.19%, in the immunogenicity of the group accounted for 8.89%, low immunogenicity was unrelated hematopoietic stem cell transplantation for 88.92%. in Sichuan Han population, according to the TCE model suggests that HLA-DPB1 may exist to allow mismatches accounted for 34.28%, the taboo mismatch in GvH and HvG directions respectively for 17.27% TCE3, while the TCE4 model allows the model does not allow the mismatch in the GJvH direction and the direction of HvG were 15.59%. (3) DPB1 transplantation sites exchange rate is allowed 5.2%. mismatch 53% families accounted for exchange found in family studies; the other 47% with.]HLA-DPB1 mismatch in the wrong taboo taboo HLA-A, -B, -DRB1 matched with cells accounted for 2.44%.[Conclusion] four HLA-DPB1 high frequency allele distribution in bone marrow in Han population, strong polymorphism, and has its own characteristics. According to the distribution of the TCE model showed that the taboo mismatch HLA-DPB1 may exist in Sichuan Han unrelated hematopoietic stem cell transplantation, tips for this attention to clinical needs. According to the TCE model analysis found that in HLA-A -B, there may be HLA-DPB1 exchange -DRB1 identical sibling, the sibling hematopoietic stem cell transplantation, taboo mismatches may also exist in HLA-DPB1.

【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R457.7

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