中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2011年
1期
92-98
,共7页
李杨%何军%鲍晓晶%邱桥成%袁晓妮%徐超%狄文英%张俭%许学明%陈子兴
李楊%何軍%鮑曉晶%邱橋成%袁曉妮%徐超%狄文英%張儉%許學明%陳子興
리양%하군%포효정%구교성%원효니%서초%적문영%장검%허학명%진자흥
人类白细胞抗原%高分辨基因分型%等位基因频率%多态性%造血干细胞移植
人類白細胞抗原%高分辨基因分型%等位基因頻率%多態性%造血榦細胞移植
인류백세포항원%고분변기인분형%등위기인빈솔%다태성%조혈간세포이식
human leukocyte antigen%high-resolution gene typing%allele frequency%polymorphism%hematopoietic stem cell transplantation
目的 从基因高分辨水平,分析中国汉族人群供-受者人类白细胞抗原(human leukocyte antigens,HLA)-A、B、Cw、DRB1、DQB1各位点等位基因频率和分布的多态性;及供-受者等位基因匹配情况.方法 采用基因测序分型(sequence based typing,SBT)、序列特异性寡核苷酸探针法(sequence specific oligonueleotide probe,SSOP)和序列特异性引物法(sequence specific primer,SSP),对2540名中国汉族人的(其中1168名受者,1372名供者)DNA标本进行HLA高分辨基因分型,并作统计学处理.结果 2540份样本中共检测到44种HLA-A等位基因,频率高于0.05的A*1101、A*2402、A*0201、A*0207、A*3303、A*0206、A*3001共占80.4%;81种HLA-B等位基因,频率高于0.05的B*4001、B*4601、B*5801、B*1302、B*5101共占43.0%;44种HLA-Cw等位基因,频率高于0.05的Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0602、Cw*0303、Cw*0302、Cw*0401共占80.3%;61种HLA-DRB1等位基因,频率高于0.05的DRB1*0901、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*0701、DRB1*0405、DRB1*0301、DRB1*1101共占70.1%;22种HLA-DQB1等位基因,频率高于0.05的DQB1*0301、DQB1*0303、DQB1*0601、DQB1*0602、DQB1*0202、DQB1*0302、DQB1*0401、DQB1*0502、DQB1*0201共占87.4%.这5个位点均处于杂合子缺失状态,其中A、B、DRB1位点符合HardyWeinberg平衡(Hardy-Weinberg equi1ibrium,HWE)(P＞0.05);Cw、DQB1位点偏离HWE(P＜0.05);排除个别基因型观察值与期望值偏差较大外,这5个位点均符合HWE.在供-受者数据的比较中,HLA全相合(10/10)的比例仅22.4%;单个等位基因错配(9/10)的比例为24.6%;两个等位基因错配(8/10)的比例为26.3%.结论 中国汉族人群高分辨水平HLA-A、B、Cw、DRB1,DQB1等位基因频率及分布特点,对非亲缘造血干细胞移植供者检索有重要参考价值;并为中华骨髓库数据入库和利用提供遗传学依据.
目的 從基因高分辨水平,分析中國漢族人群供-受者人類白細胞抗原(human leukocyte antigens,HLA)-A、B、Cw、DRB1、DQB1各位點等位基因頻率和分佈的多態性;及供-受者等位基因匹配情況.方法 採用基因測序分型(sequence based typing,SBT)、序列特異性寡覈苷痠探針法(sequence specific oligonueleotide probe,SSOP)和序列特異性引物法(sequence specific primer,SSP),對2540名中國漢族人的(其中1168名受者,1372名供者)DNA標本進行HLA高分辨基因分型,併作統計學處理.結果 2540份樣本中共檢測到44種HLA-A等位基因,頻率高于0.05的A*1101、A*2402、A*0201、A*0207、A*3303、A*0206、A*3001共佔80.4%;81種HLA-B等位基因,頻率高于0.05的B*4001、B*4601、B*5801、B*1302、B*5101共佔43.0%;44種HLA-Cw等位基因,頻率高于0.05的Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0602、Cw*0303、Cw*0302、Cw*0401共佔80.3%;61種HLA-DRB1等位基因,頻率高于0.05的DRB1*0901、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*0701、DRB1*0405、DRB1*0301、DRB1*1101共佔70.1%;22種HLA-DQB1等位基因,頻率高于0.05的DQB1*0301、DQB1*0303、DQB1*0601、DQB1*0602、DQB1*0202、DQB1*0302、DQB1*0401、DQB1*0502、DQB1*0201共佔87.4%.這5箇位點均處于雜閤子缺失狀態,其中A、B、DRB1位點符閤HardyWeinberg平衡(Hardy-Weinberg equi1ibrium,HWE)(P＞0.05);Cw、DQB1位點偏離HWE(P＜0.05);排除箇彆基因型觀察值與期望值偏差較大外,這5箇位點均符閤HWE.在供-受者數據的比較中,HLA全相閤(10/10)的比例僅22.4%;單箇等位基因錯配(9/10)的比例為24.6%;兩箇等位基因錯配(8/10)的比例為26.3%.結論 中國漢族人群高分辨水平HLA-A、B、Cw、DRB1,DQB1等位基因頻率及分佈特點,對非親緣造血榦細胞移植供者檢索有重要參攷價值;併為中華骨髓庫數據入庫和利用提供遺傳學依據.
목적 종기인고분변수평,분석중국한족인군공-수자인류백세포항원(human leukocyte antigens,HLA)-A、B、Cw、DRB1、DQB1각위점등위기인빈솔화분포적다태성;급공-수자등위기인필배정황.방법 채용기인측서분형(sequence based typing,SBT)、서렬특이성과핵감산탐침법(sequence specific oligonueleotide probe,SSOP)화서렬특이성인물법(sequence specific primer,SSP),대2540명중국한족인적(기중1168명수자,1372명공자)DNA표본진행HLA고분변기인분형,병작통계학처리.결과 2540빈양본중공검측도44충HLA-A등위기인,빈솔고우0.05적A*1101、A*2402、A*0201、A*0207、A*3303、A*0206、A*3001공점80.4%;81충HLA-B등위기인,빈솔고우0.05적B*4001、B*4601、B*5801、B*1302、B*5101공점43.0%;44충HLA-Cw등위기인,빈솔고우0.05적Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0602、Cw*0303、Cw*0302、Cw*0401공점80.3%;61충HLA-DRB1등위기인,빈솔고우0.05적DRB1*0901、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*0701、DRB1*0405、DRB1*0301、DRB1*1101공점70.1%;22충HLA-DQB1등위기인,빈솔고우0.05적DQB1*0301、DQB1*0303、DQB1*0601、DQB1*0602、DQB1*0202、DQB1*0302、DQB1*0401、DQB1*0502、DQB1*0201공점87.4%.저5개위점균처우잡합자결실상태,기중A、B、DRB1위점부합HardyWeinberg평형(Hardy-Weinberg equi1ibrium,HWE)(P＞0.05);Cw、DQB1위점편리HWE(P＜0.05);배제개별기인형관찰치여기망치편차교대외,저5개위점균부합HWE.재공-수자수거적비교중,HLA전상합(10/10)적비례부22.4%;단개등위기인착배(9/10)적비례위24.6%;량개등위기인착배(8/10)적비례위26.3%.결론 중국한족인군고분변수평HLA-A、B、Cw、DRB1,DQB1등위기인빈솔급분포특점,대비친연조혈간세포이식공자검색유중요삼고개치;병위중화골수고수거입고화이용제공유전학의거.
Objective To analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients. Methods HLA highresolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out. Results Forty-four HLA-A alleles were detected, and among them the frequencies of A * 1101, A * 2402, A * 0201, A * 0207, A * 3303, A *0206 and A * 3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and frequencies of B * 4001, B * 4601, B * 5801, B * 1302 and B * 5101 exceeded 0. 05, and accounted for 43. 0% of total. There were 44 HLA- Cw alleles, among them the frequencies of Cw * 0702, Cw * 0102,Cw * 0304, Cw * 0801, Cw * 0602, Cw * 0303, Cw * 0302 and Cw * 0401 exceeded 0.05, and were 80.3 %of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1 * 0901, DRB1 * 1501, DRB1 * 1202,DRB1 * 0803, DRB1 * 0701, DRB1 * 0405, DRB1 * 0301 and DRB1 * 1101 exceeded 0. 05, and were 70. 1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1 * 0301, DQB1 *0303, DQB1 * 0601, DQB1 * 0602, DQB1 * 0202, DQB1 * 0302, DQB1 * 0401, DQB1 * 0502 and DQB1 *0201 exceeded 0. 05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P＞0. 05); but HLA-Cw and HLA-DQB1 loci did not (P＜0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24. 6% of recipients found single HLA allele mismatched donors (9/10); 26. 3% of recipients had two HLA alleles mismatched donors (8/10). Conclusion The characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.
