造血干细胞移植受-供者HLA抗原识别部位的核苷酸匹配研究

目的 研究中国人群等待造血干细胞移植受-供者人类白细胞抗原(human leukocyte antigens,HLA)-A、-B、-Cw、-DRBl、-DQB1 5个位点的等位基因及核苷酸匹配情况,从单核苷酸水平探讨最佳供选择方案.方法 采用聚合酶链反应测序分型法(polymerase chain reaction-sequence-based typing,PCR-SBT),对537对中国人群等待造血干细胞移植受-供者HLA-A、-B、-Cw、-DRB1、-DQB1位点的等位基因进行序列分型,应用BLAST工具分析受-供者HLA核苷酸差异.结果 37对受-供者中HLA-A、-B、-Cw、-DRB1、-DQB1五位点核苷酸完全匹配占16.20%,单个等位基因错配的受-供者对分别占8.38%,0.74%,12.29%,2.42%和2.79%,两个或两个以上等位基因错配比率占42.65%.检出A*02:01-A*02:06,A*02:06-A*02:07,Cw*03:04-Cw*15:02,Cw*03:03-Cw*04:01,Cw*03:04-Cw*14:02,Cw *03:03-Cw*08:01,DRB1*04:03:01-DRB1*04:05不容许错配等位基因对.两对受-供者B*07:05:01-B*07:06,Cw*07:01:01-Cw*07:06抗原识别区外核苷酸错配.结论 在造血干细胞移植选择HLA错配的无关供者时注意受-供核苷酸匹配差异,对HLA抗原识别区内的核苷酸匹配差异和抗原识别区外的核苷酸匹配差异应当加以区别.本研究结果为优化供者选择顺序提供科学参考数据.     

Study of polymorphisms of HLA class i (-A, -B, -C) and class i (DRB1 , DQA1 , DQB1 , DPA1 , DPB1) genes among ethnic Hans from Southern China北大核心CSCD

Objective To study the genetic polymorphisms of human leukocyte antigen {HLA)- A, B, C, DRB1 , DQA1 , DQB1 , DPA1 and DPB1 among ethnic Hans from southern China. Methods 481 randomly selected individuals were genotyped using a polymerase chain reaction (PCR) sequence-based typing (SBT) method for the above genes. Their allelefrequencies were determined by direct counting. Results In total, 28 HLA-A, 57 HLA-B, 28 HLA-C, 40 HLA-DRB1 ,18 HLA-DQA1 , 17 HLA-DQB1 , 6 HLA-DPA1 and 21 HLA-DPB1 alleles were identified. Among these, common alleles(with allelic frequencies > 0.05) included A∗1101, A∗2402, A∗0207, A∗3303, A∗0201, B∗40:01, B∗46:01, B∗58:01, B∗13:01, B∗15:02, C∗01:02, C∗07:02, C∗03:04, C∗03:02, C∗08:01, C∗03:03, C∗04:01, DRB1∗09:01, DRB1∗15:01, DRB1∗12:02, DRB1∗08:03, DRB1∗03:01, DRB1∗04:05, DRB1∗11:01, DQA1∗01:02, DQA1∗03:02, DQA1∗03:03, DQA1∗06:01, DQA1∗01:03, DQA1∗05:05, DQA1∗01:04, DQA1∗03:01, DQA1∗05:01, DQB1∗03:01, DQB1∗03:03, DQB1∗06:01, DQB1∗05:02, DQB1∗03:02, DQB1∗02:01, DQB1∗03:02, DQB1∗06:02, DPA1∗02:02, DPA1∗01:03, DPAl∗02:01, DPB1∗05:01, DPB1∗02:.01, DPB1∗13:01, DPB1∗04:01 andDPB1∗02:02. For each of the locus, the overall frequencies of common alleles were 75. 57%, 52. 81%, 78. 28%, 62. 16% , 86. 70% , 77. 23% , 95. 32% and 81. 59% , respectively. Conclusion The allelic frequencies of the 8 selected HLA loci among ethnic Hans from southern China may served as a reference for anthropology, legal medicine, transplantation and disease association studies.     

The distribution of HLA-A, -B, and -DRB1 alleles and haplotypes in inhabitants of Guizhou Province of China

The present study was aimed to analyze the frequencies of human leukocyte antigen (HLA)-A,-B,and-DRB1 alleles and A-B-DRB1,A-B,A-DRB1 and B-DRB1 haplotypes in inhabitants of Guizhou province,China.All samples were typed in the HLA-A,-B,and-DRB1 loci using the polymerase chain reaction-reverse sequence specific oligonucleotide probe (PCR-rSSOP) method and HLA polymorphisms were analyzed.A total of 18 HLA-A,31 HLA-B,and 13 HLA-DRB1 alleles were found in the Guizhou population.The first two frequent alleles in the HLA-A,-B,and-DRB1 loci were A11(30.72%) and A02(30.65%),B40(16.27%) and B46(16.27%),and DRB109(15.91%) and DRB115(13.51%),respectively.The most common haplotype was A02-B46DRB109(5.59%) in A-B-DRB1,A02-B46(11.73%) in A-B,B46-DRB109(7.49%) in B-DRB1,and A02DRB109(8.08%) in A-DRB1.Some haplotypes with strong linkage disequilibrium (LD) were found not only in the common haplotypes,such as A33-B58,B30-DRB107,and B33-DRB103,but also in the rare haplotypes,such as A01-B37,B37-DRB110,and A01-DRB110.Guizhou inhabitants shared some characteristics of the Southern Chinese population but also had their own unique features.Overall,HLA polymorphism in Guizhou population was more consistent with that of Chengdu population than that of other populations in China.     

江苏7地市汉族人群HLA-DRB1等位基因多态性分析

目的 分析江苏7地市汉族造血干细胞捐献志愿者人类白细胞抗原(HLA)-DRB1位点的基因频率,研究比较该7地市人群HLA-DRB1基因多态性.方法 采用聚合酶链反应-直接测序分型(PCR-SBT)和聚合酶链反应-反向序列特异性寡核苷酸探针(PCR-rSSOP)基因分型技术,对中华骨髓库江苏分库2787名无关供者的HLA-DRB1位点进行高分辨分型,分别计算并比较各地市HLA-DRB1基因频率.结果 淮安、徐州、泰州、宿迁、南京、常州、扬州HLA-DRB1位点分别检出等位基因38、33、26、36、37、31、26个.在淮安、徐州、宿迁,频率最高的HLA-DRB1等位基因分别是DRB1*07:01、09:01、15:01、12:02.在南京,频率最高的HLA-DRB1等位基因分别是DRB1*09:01、07:01、15:01、12:02.在扬州,频率最高的HLA-DRB1等位基因分别是DRB1*09:01、07:01、15:01、08:03.在泰州,频率最高HLA-DRB1等位基因是DRB1*09:01、07:01、04:05、15:01;在常州,频率最高的HLA-DRB1等位基因是DRB1*09:01、07:01、12:02、08:03.结论 本资料反映了江苏7地市汉族人群HLA-DRB1基因分布,具有丰富的多态性,其中南京、扬州基因频率相近最接近中国北方群体的特征.淮安、徐州、宿迁、常州、泰州5地市相近,除了DRB1*09:01、07:01两高频基因频率有所差异外也接近中国北方.本研究为HLA与疾病相关研究和我国人群群体遗传学研究等提供有意义的基础性资料.

Abstract：

Objective To investigate the frequencies of human leukocyte antigen ( HLA)-DRB1 alleles of Chinese Marrow Donor Program (CMDP) donors in seven markets of Jiangsu Han population. Methods 2787 donors from CMDP Jiangsu Branch were typed in HLA-DRB1 locus using polymerase chain reaction-sequence-based typing (PCR-SBT) method or polymerase chain reaction-reverse sequence specific oligonucleotide probes (PCR-rSSOP) method. Frequencies of HLA-DRB1 were separately calculated in seven markets and a comparison was made among them. Results A total of 38,33,26,36,37,31,26 alleles in DRB1 locus were separately found in Huai-an, Xuzhou, Taizhou, Suqian, Nanjing, Changzhou, Yangzhou population. The most frequent HLA-DRB1 alleles in Huai-an, Xuzhou, Suqian respectively were DRB1 * 07:01, 09:01, 15:01,12:02; In Nanjing and were DRB1 * 09:01,07:01, 15:01, 12:02; In Yangzhou were DRB1 * 09:01,07:01,15:01,08:03; In Taizhou were DRB1 *09:01, 07:01, 04:05, 15:01; In Changzhou were DRB1 *09:01,07:01, 12:02, 08:03. Conclusion The above results reflected the distribution of HLA-DRB1 alleles in seven markets of Jiangsu Han population, which held abundant polymorphism, and a certain uniqueness in every market. The HLA-DRB1 allele distribution of Nanjing, Yangzhou were the closest groups to northern China, Huaian, Xuzhou, Suqian, Changzhou, Taizhou were close to northern China except DRB1 * 09:01,07:01 in different frequencies. These findings could guide the selection of future donor in CMDP Jiangsu Branch. It also could serve as foundation for HLA related disease research, studies of population genetics and anthropology in Chinese Han population.     

HBV感染者HLA-Ⅰ类和HLA-Ⅱ类基因单倍型分析

目的 本研究对黑龙江地区乙型肝炎病毒(HBV)感染者进行了人类白细胞抗原(HLA)Ⅰ类和Ⅱ类基因单倍型分析,并结合HBV-C2亚型探讨其与HBV感染者最终清除病毒和慢性持续的关系.方法 本研究共230个HBV感染者与210个健康无血缘关系健康人作为对照进行比较,并对所有患者进行了HLA等位基因分型和单倍型的连锁分析.结果 本地区最常见的单倍型是A*02-B*40.A*02-DRB1*08,A*02-DRB1*09,A*02-DRB1*12,A术11-DRB1*15,A*24-DRB1*09,A*33-DRB1*07,B*13-DRB1*12,B*15-DRB1*15,B*40-DRB1*08,B*40-DRB1* 09,B*51-DRB1* 09,B*51-DRB1*15,和A*02-B* 15-DRB1* 09携带者可能更易于感染HBV,而A*24-B*13,B*13-DRB1*09,A*02-DRB1*07,A*33-DRB1*13,A*33-DRB1*15,和A* 02-B* 40-DRB1* 15可能保护机体免受HBV感染.另外A*02-DRB1* 12可能还与病毒持续慢性感染相关.感染HBV C2亚型病毒后,A*24-DRB1* 14,B*15-DRB1* 04,A*02-B* 15,A*02-DRB1* 15和A*02-B15-DRB1* 09携带者可能伴有急性的临床发作过程并最终清除病毒.结论 本研究报道了HLA单倍型与HBV感染亚型与感染者临床预后的关系,对HBV的潜在的靶向治疗提供了一定的理论基础.     

HLA-A*02:251新等位基因克隆测序鉴定及序列分析

目的 鉴定中国人群人类白细胞抗原(human leukocyte antigen,HLA)A*02:251新等位基因,分析新等位基因遗传特征.方法 采用聚合酶链反应-测序分型法(polymerase chain reaction-sequence based typing,PCR-SBT)对组织配型健康供、患者进行HLA基因分型,发现先证者核苷酸杂合序列与已知序列不匹配,不能指定先证者HLA等位基因型,对先证者DNA扩增HLA-A位点第2～4外显子,PCR产物经克隆到PMD18-T质粒载体中以获得单链核苷酸序列,对克隆所得产物进行HLA-A基因的第2～4外显子双向测序分析.结果 发现先证者的一个HLA-A*02:06:01基因被确认,而另一个HLA-A基因为新等位基因,其序列被GenBank接受(编号为HM245348).新等位基因序列通过IMGT/HLA 数据库BLAST,与最相近的A*02:01:01:01相比,在第3外显子上有1个核苷酸的不同,即第383位 G>C,密码子 128 GAG→GAC,氨基酸由谷氨酸(Glu)→天门冬氨酸(Asp).供、患者HLA-A、B、C、DQB1位点等位基因不匹配.结论 该等位基因为新的HLA-A*02:251等位基因.中国人群HLA-A 位点第3外显子核苷酸序列存在多态性.

Abstract：

Objective To identify a novel human leukocyte antigen (HLA) allele A*02:251 and analyze the sequences in Chinese population. Methods Routine HLA-A, -B, -DRB1 high resolution genotyping for healthy Chinese donors and patients was performed with polymerase chain reaction-sequence based typing. An unknown HLA-A allele was initially detected by HLA typing in the healthy donor. Genomic DNA of the HLA-A locus in the proband was amplified, the amplified product was cloned by PMD18-T to split the two alleles, and selected clones were sequenced. Results The sequencing results showed that a normal A*02:06:01 and a novel A*02:251 variant allele were identified. The sequence of the novel allele has been submitted to GenBank (HM245348). Nucleotide sequence alignments with HLA-A allele from the IMGT/HLA Sequence Database showed that the novel A*02 variant allele differed from the closest allele A*02:01:01:01 by nt 383 G>C (codon 128 GAG>GAC) in exon 3, which resulted in one amino acid substitution of Glu>Asp. The HLA-A, B, C and DQB1 alleles of the healthy donor did not match with that of the patient. Conclusion This novel allele is officially designated as HLA-A*02:251 by World Health Organization(WHO) Nomenclature Committee (Submission ID HWS10010755). The sequence of HLA-A locus in exon 3 is confirmed to be polymorphic in Chinese population.     

造血干细胞移植志愿捐献者罕见基因人类白细胞抗原C*08:99的测序分析

BACKGROUND: As the sequencing technology has been widely used and high-resolution confirmation of organ transplant matching has been gradually developed, new human leukocyte antigen (HLA) alleles are emerging. However, the gene frequency of some genes cannot be calculated accurately, and there are rare reports. These genes are often ignored, and it is easy to misjudge their genotypes only according to gene frequency. OBJECTIVE: To test and analyze a rare allele, HLA-C*08:99, from a volunteer donor of hematopoietic stem cell transplantation.METHODS:Genomic DNA was extracted automatically from the blood sample by using quick DNA purified kit and amplified by HLA-C locus commercial sequence-based typing kit. The purified PCR product was utilized as the DNA template in the sequencing reaction, and six direct sequencing reactions of PCR product covering exons 2, 3 and 4 in both directions were performed using commercial kit. Four direct sequencing reactions of PCR product covering exon 5 in both directions, exon 6 in forward direction and exon 7 in reverse direction were performed using in-house BigDye terminator cycle sequencing reaction kit. Sequencing reaction products purified by ethanol/sodium acetate/ ethylenediaminetetraacetic acid method were sequenced by ABI PrismTM3730 DNA Sequencer.RESULTS AND CONCLUSION: The allele assignment was analyzed with Assign-SBT 3.6+ software, and the sample HLA-C typing result was C*07:04, 08:99. Increasing the sequencing analysis at exons 5, 6 and 7 of HLA-C locus will help to make clear the ambiguous SBT result and improve the accuracy of HLA-C typing when it is necessary, which shows important significance in clinical tissue matching.  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

新疆地区汉族和维吾尔族部分人群HLA-DRB1、HLA-DQB1、HLA-DPB1基因多态性与单倍型的比较

目的了解中国新疆维吾尔自治区汉族和维吾尔族人类白细胞抗原DRB1(HLA-DRB1)、HLA-DQB1、HLA-DPB1高分辨分型基础上的基因多态性和单倍型分布的特点。方法应用聚合酶链反应-直接测序基因分型(PCR-SBT)法对新疆地区188例汉族人群与90例维吾尔族人群进行HLA-DRB1、HLA-DQB1、HLA-DPB1基因分型,直接计数法计算基因频率,应用Arlequin3.5软件以最大似然法获得单倍型频率。结果汉族人群频率最高的HLA-Ⅱ类基因分别是DRB1*09∶01(12.8%)、DQB1*03∶01(20.3%)和DPB1*05∶01(33.5%);三位点组成的单倍型频率最高的分别是DRB1*09∶01-DQB1*03∶03(8.8%)、DRB1*09∶01-DPB1*05∶01(5.0%)、DQB1*03∶01-DPB1*05∶01(9.6%)和DRB1*09∶01-DQB1*03∶03-DPB1*05∶01(6.3%)。维吾尔族人群频率最高的HLA-Ⅱ类基因分别是DRB1*07∶01(18.3%)、DQB1*03∶01(18.9%)和DPB1*04∶01(30.0%);三位点组成的单倍型频率最高的分别是DRB1*07∶01-DQB1*02∶02(16.1%)、DRB1*07∶01-DPB1*04∶01(5.0%)、DQB1*03∶01-DPB1*04∶01(7.3%)、DRB1*07∶01-DQB1*02∶02-DPB1*04∶01(7.4%)。两组人群中等位基因有显著差异的是∶DRB1*04∶04、DRB1*07∶01、DRB1*08∶03、DRB1*11∶04、DRB1*12∶02、DRB1*13∶01、DRB1*15∶01、DQB1*02∶02、DQB1*06∶01、DPB1*04∶01和DPB1*05∶01。结论中国新疆汉族与维吾尔族人群HLA-DRB1、HLA-DQB1、HLA-DPB1等位基因频率、单倍型频率分布均有自己的多态性特征。     

广西汉族人群HLA-A、-B、-DRB1高分辨等位基因和单倍型多态性的初步分析

目的分析广西汉族人群人类白细胞抗原(human leukocyte antigen,HLA)-A、-B、-DRB1等位基因和单倍型的分布特征。方法采用多聚酶链式反应-基于测序的分型技术(polymerase chain reaction-sequence based typing,PCR-SBT)对广西地区1 644名汉族无关个体进行HLA-A、-B、-DRB1等位基因和单倍型多态性的分型,使用Arlequin软件(3.5.2.2)计算HLA等位基因频率、单倍型频率和连锁不平衡参数。使用MEGA v6.0软件构建系统发生树,并与其他部分中国汉族人群的基因频率进行比较。结果该人群HLA-A、-B、-DRB1等位基因分布均偏离Hardy-Weinberg平衡(P0.05),3个位点分别检出37种HLA-A,70种HLA-B和37种HLA-DRB1等位基因。其中,等位基因频率分布最高的分别是A~*11∶01(28.86%)、B~*46∶01(14.26%)和DRB1~*15∶01(13.32%),最常见的单倍型是A~*33:03-B~*58∶01-DRB1~*03∶01(6.12%),A~*02∶07-B~*46∶01、A~*11∶01-DRB1~*15∶01和B~*58∶01-DRB1~*03∶01呈现最强的连锁不平衡。该人群与广西壮族人群亲缘关系最近,其多态性最接近的汉族是中国南方汉族。结论广西汉族人群HLA-A、-B、-DRB1等位基因和单倍型有较高的遗传多态性,将为中国人群在临床寻找HLA匹配的无关亲缘供者、法医学研究以及人类学研究等提供有价值的遗传学依据。     

用等位基因组特异性引物扩增技术确认HLA-B新等位基因B*15:129

目的 对人类白细胞抗原(human leukocyte antigen,HLA)新等位基因HLA-B*15:129的第2～4外显子序列进行分析.方法 采用商用抽提试剂盒抽提标本DNA,应用等位基因组特异性引物PCR方法扩增先证者标本HLA-B基因第2～4外显子,PCR产物经酶切纯化后直接进行HLA-B基因第2～4外显子双向测序分析.结果 先证者标本存在2个HLA-B等位基因,1个等位基因为B*07:02,另1个经Blast验证为新的等位基因,新的等位基因序列已递交GenBank(EF473219),经世界卫生组织HLA命名委员会正式命名为HLA-B*15:129.HLA-B*15:129第2～4外显子序列与最接近的B*15:01:01:01相比,第3外显子存在3个碱基的不同,即第362位G→A、363位G→T、369位C→T改变,导致第97位氨基酸Arg→Asn.结论 发现1例新的HLA-B等位基因,被世界卫生组织HLA基因命名委员会正式命名为HLA-B*15:129.

Abstract：

Objective To analyze the sequence of the exons 2-4 of human leukocyte antigen (HLA) novel allele HLA-B*15:129.Methods DNA of the proband was extracted from whole blood by commercial DNA extraction kit. The amplification for HLA-B exons 2-4 was performed separately by polymerase chain reaction (PCR) with allele group specific primers. The PCR products were digested with enzymes and then directly sequenced for exons 2-4 of HLA-B locus in both directions.Results Sequencing results showed the HLA-B alleles of the proband included B*07:02 and a novel allele. The sequence of the novel allele has been submitted to GenBank (accession no. EF473219) and the allele has been officially named B*15:129 by the WHO Nomenclature Committee. Comparing with the HLA-B*15:01:01:01, the sequence of exons 2-4 of HLA-B*15:129 showed three nucleotide difference in exon 3 at positions 362 and 363 from GG to AT and positions 369 from C to T, which resulted in an amino acid change from Arg to Asn at codon 97.Conclusion A novel HLA-B allele was identified and has been officially named B15:129 by the WHO Nomenclature Committee.     

A single center study of protective and susceptible HLA alleles and haplotypes with end-stage renal disease in China

Chronic kidney disease (CKD) is becoming a global public health problem and usually cause End-Stage Renal Disease (ESRD) in the end of progression. To analyze the associations of HLA-A, -B, -C, -DRB1 and -DQB1 alleles at high resolution with ESRD in Jiangsu province of China, a total of 499 unrelated patients with ESRD from the First Affiliated Hospital with Nanjing Medical University and 1584 healthy controls from Jiangsu Branch of Chinese Marrow Donor Program (CMDP) were genotyped at HLA-A, -B, -C, -DRB1 and -DQB1 loci. Statistical analysis was applied to compare the differences of HLA allele frequencies between patients with ESRD and healthy controls. As results, no protective allele at A locus was found and the susceptible alleles were A*11:01 and A*31:01. At B locus, B*15:01, B*55:02 and B*39:05 emerged as susceptible alleles, whereas no protective allele was found. At C locus, C*06:02 and C*07:01 emerged as protective alleles and no susceptible allele was found. At DRB1 locus, six alleles including DRB1*03:01, DRB1*04:03, DRB1*04:04, DRB1*04:05, DRB1*11:01 and DRB1*12:02 emerged as susceptible alleles, while DRB1*15:01 emerged as a protective allele. At DQB1 locus, DQB1*02:01, DQB1*03:01, DQB1*03:02 and DQB1*04:01 emerged as susceptible alleles, while DQB1*06:02 and DQB1*06:09 emerged as protective alleles. Haplotype A*11:01-C*03:03-B*15:01-DRB1*11:01-DQB1*03:01 containing four susceptible alleles was regarded as the most susceptible haplotype. The susceptible alleles and haplotypes might be used as some important risk classification markers. Besides, in the consanguineous renal transplantation, it would be very beneficial for the long-term survival of renal transplant patients to avoid the susceptible alleles and haplotypes in selecting optimal donors.     

Genetic link among Hani,Bulang and other Southeast Asian populations: evidence from HLA -A, -B, -C, -DRB1 genes and haplotypes distribution

Human leucocyte antigen (HLA) genetic characteristic of different ethnic minorities would be useful for tracing the origin of modern human HLA matching in transplantation and disease associations. In this study, we reported HLA-A, -B, -C and -DRB1 alleles and haplotypes in the Bulang and Hani populations of southwestern China using a high-resolution polymerase chain reaction-Luminex (PCR-Luminex) typing method. A total of nine HLA-A, 22 HLA-B, 13 HLA-C and 18 HLA-DRB1 alleles were identified in the Bulang population, and 11 HLA-A, 25 HLA-B, 14 HLA-C and 19 HLA-DRB1 alleles were in the Hani population. Compared with other populations, the predominant A*1101-B*1502-DRB1*1202 haplotype in the Bulang and Hani populations was also common in Jinuo, Wa, Dai, Maonan and Vietnamese populations. The distribution of HLA genes indicate that Bulang and Hani populations belong to the Southeast Asia group and they have maintained their original genetic characteristics and kept a long genetic distance from other populations owing to founder effects and subsequent geographic isolation. In addition, the close relationship among ethnic groups in Yunnan province and the Thai and Vietnamese populations were confirmed, whereas the Mon-Kmer-speaking populations shared other common HLA alleles and haplotypes compared with other linguistic groups.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Study on the polymorphisms of HLA‐ABCDQB1DRB1 alleles and haplotypes in Hubei Han population of China

The present study aimed to analyse the frequencies of human leukocyte antigen HLA‐ABCDQB1 and HLA‐DRB1 alleles and haplotypes in a subset of 3,732 Han population from Hubei of China. All samples were typed in the HLA‐ABCDQB1 and HLA‐DRB1 loci using the sequence‐based typing method; subsequently, the HLA polymorphisms were analysed. A total of 47 HLA‐A, 89 HLA‐B, 43 HLA‐C, 49 HLA‐DRB1 and 24 HLA‐DQB1 alleles were identified in the Hubei Han population. The top three most frequent alleles in the HLA‐ABCDQB1 and HLA‐DRB1 were A*11:01 (0.2617), A*24:02 (0.1590), A*02:07 (0.1281); B*46:01 (0.1502), B*40:01 (0.1409) and B*58:01 (0.0616); C*01:02 (0.2023), C*07:02 (0.1691) and C*03:04 (0.1175); and DQB1*03:01 (0.2000), DQB1*03:03 (0.1900), DQB1*06:01 (0.1187); DRB1*09:01 (0.1790), DRB1*15:01 (0.1062) and DRB1*12:02 (0.0841), respectively. Meanwhile, the three most frequent two‐loci haplotypes were A*02:07‐C*01:02 (0.0929), B*46:01‐C*01:02 (0.1366) and DQB1*03:03‐DRB1*09:01 (0.1766). The three most frequent three‐loci haplotypes were A*02:07‐B*46:01‐C*01:02 (0.0883), B*46:01‐DQB1*03:03‐DRB1*09:01 (0.0808) and C*01:02‐DQB1*03:03‐DRB1*09:01 (0.0837). The three most frequent four‐loci haplotypes were A*02:07‐B*46:01‐C*01:02‐DQB1*03:03 (0.0494), B*46:01‐DRB1*09:01‐C*01:02‐DQB1*03:03 (0.0729) and A*02:07‐B*46:01‐DQB1*03:03‐DRB1*09:01 (0.0501). The most frequent five‐loci haplotype was A*02:07‐B*46:01‐C*01:02‐DQB1*03:03‐DRB1*09:01 (0.0487). Heat maps and multiple correspondence analysis based on the frequencies of HLA specificity indicated that the Hubei Han population might be described into Southern Chinese populations. Our results lay a certain foundation for future population studies, disease association studies and donor recruitment strategies.     

西北地区汉族人群HLA-A、-B、-DRB1基因座单倍型分析

目的 分析西北地区汉族群体HLA-A、-B和-DRB1基因座等位基因频率和HIA-A-B、B-DRB1和A-B-DRB1单倍型，获得单倍型频率数据。方法 采用序列特异性寡核苷酸探针反向斑点杂交技术对西北地区62个家系和101个无关个体HLA-A、-B和-DRB1基因座进行基因分型，分析HLA单倍型。结果 在西北地区汉族人群中检出15个HLA-A等位基因，28个HLA-B等位基因，13个HLA-DRB1等位基因，A02、A11、A24、B13、B15、1340、DRB1＊04、DRB1＊07、DRB1＊09和DRB1＊15基因频率较高（〉10％），A02（0．3244）、B13（0．1200）和DRB1＊15（0．1400）等位基因频率最高。分析得出HLA-A-B、B-DRB1、A-B-DRB1单倍型分别有122、147和278种，83种A-B-DRB1单倍型有至少两条以上相同的单倍型，占总单倍型数的18．44％（83／450）。A30-B13-DRB1＊07、A02-B46-DRB1＊09、A01-B37-DRB1＊10、A24-B15-DRB＊15、A02-B46-DRB1＊08、A33-B58-DRB1＊03是最常见的单倍型。结论 西北地区汉族群体HLA单倍型多态性较为丰富，等位基因频率和单倍型频率数据可用于骨髓移植供者的选择、法医学亲权鉴定以及人类学研究。     

Human leukocyte antigen–A, -B, -C, -DRB1 allele and haplotype frequencies in Americans originating from southern Europe: Contrasting patterns of population differentiation between Italian and Spanish Americans

High-resolution DNA sequencing was used to identify the human leukocyte antigen (HLA) –A, -B, -C, and -DRB1 alleles found in 552 individuals from the United States indicating Southern European (Italian or Spanish) heritage. A total of 46 HLA-A, 80 HLA-B, 32 HLA-C, and 50 DRB1 alleles were identified. Frequent alleles included A*02:01:01G (allele frequency = 0.26 in Italian Americans and 0.22 in Spanish Americans); B*07:02:01G (Italian Americans allele frequency = 0.11); B*44:03 (Spanish Americans allele frequency = 0.07); C*04:01:01G and C*07:01:01G (allele frequency = 0.13 and 0.16, respectively, in Italian Americans; 0.15 and 0.12, respectively, in Spanish Americans); and DRB1*07:01:01 (allele frequency = 0.12 in each population). The action of balancing selection was inferred at the HLA-B and -C loci in both populations. The A*01:01:01G-C*07:01:01G-B*08:01:01G-DRB1*03:01:01 haplotype was the most frequent A-C-B-DRB1 haplotype in Italian Americans (haplotype frequency = 0.049), and was the second most frequent haplotype in Spanish Americans (haplotype frequency = 0.021). A*29:02:01-C*16:01:01-B*44:03-DRB1*07:01:01 was the most frequent A-C-B-DRB1 in Spanish Americans (haplotype frequency = 0.023), and was observed at a frequency of 0.015 in Italian Americans. Pairwise F′_st values measuring the degree of differentiation between these Southern European American populations as well as European and European American populations suggest that Spanish Americans constitute a distinct subset of the European American population, most similar to Mexican Americans, whereas Italian Americans cannot be distinguished from the larger European American population.     

HLA class I diversity in Kolla Amerindians

Human leukocyte antigen (HLA) class I polymorphism was studied within a population of 70 unrelated Kolla Amerindians from the far northwest of Argentina close to the Bolivian border. The results indicate that the HLA-A, -B, and -C alleles typical of other Amerindian populations also predominate in the Kolla. These alleles belong to the following allele groups: HLA-A*02, *68, *31, *24, HLA-B*35, *15, *51, *39, *40, *48, and Cw*01, *03, *04, *07, *08, and *15. For the HLA-A locus, heterogeneity was seen for HLA-A*02 with A*0201, *0211, and *0222; and for A*68 with *68012 and *6817, the latter being a novel allele identified in this population. Analysis of HLA-B identified heterogeneity for all Amerindian allele groups except HLA-B*48, including the identification of the novel B*5113 allele. For HLA-C heterogeneity was identified within the Cw*07, *04, and *08 groups with Cw*0701/06, *0702, *04011, *0404, *0803, and *0809 identified. The most frequent "probable" haplotype found in this population was B*3505-Cw*04011. This study supports previous studies, which demonstrate increased diversity at HLA-B compared with HLA-A and -C. The polymorphism identified within the Kolla HLA-A, -B, and -C alleles supports the hypothesis that HLA evolution is subject to positive selection for diversity within the peptide binding site.     

Polymorphism of human leukocyte antigen-A, -B, and -DRB1 in a Moroccan population from Casablanca: study of the allelic and the haplotypic frequencies

We have studied the distribution of HLA-A, -B and DRB1 alleles and haplotypes by sequence specific oligonucleotide amplification in a sample of 125 unrelated healthy Moroccan individuals from Casablanca in Morocco. The city of Casablanca is known of its big ethnic diversity, especially Arabs and Berbers. The most frequent alleles found were: HLA-A*02 (18.4%), -A*01 (11.2%), -A*03 (10.8%), -B*51 (8.06%),-B*44 (7.66%), -B*08 (6.85%), -DRB1*04 (15.98%), DRB1*03 and DRB1*07 (13.92%) and -DRB1*01 (10%). High frequency for five two-locus haplotypes was observed for A*03-B*51 (5%), A*02-DRB1*03 (5.5%), A*02-DRB1*04 and A*01-DRB1*04 (5%) and B*35-DRB1*04 (4%). No predominant haplotype was observed for HLA A-B-DRB1. Our results confirm and extend the current knowledge about genetic pattern of the Moroccan of Casablanca. This study will serve as a reference for further anthropological studies, as well as studies of HLA and disease associations in the Moroccan population.     

The association of human leucocyte antigen (HLA) alleles with COVID-19 severity: A systematic review and meta-analysis

Due to their pivotal role in orchestrating the immune response, HLA loci were recognized as candidates for genetic association studies related to the severity of COVID-19. Since the findings on the effects of HLA alleles on the outcome of SARS-CoV-2 infection remain inconclusive, we aimed to elucidate the potential involvement of genetic variability within HLA loci in the molecular genetics of COVID-19 by classifying the articles according to different disease severity/outcomes and by conducting a systematic review with meta-analysis. Potentially eligible studies were identified by searching PubMed, Scopus and Web of Science literature databases. A total of 28 studies with 13,073 participants were included in qualitative synthesis, while the results of 19 studies with 10,551 SARS-CoV-2-positive participants were pooled in the meta-analysis. According to the results of quantitative data synthesis, association with COVID-19 severity or with the lethal outcome was determined for the following alleles and allele families: HLA-A*01, HLA-A*03, HLA-A*11, HLA-A*23, HLA-A*31, HLA-A*68, HLA-A*68:02, HLA-B*07:02, HLA-B*14, HLA-B*15, HLA-B*40:02, HLA-B*51:01, HLA-B*53, HLA-B*54, HLA-B*54:01, HLA-C*04, HLA-C*04:01, HLA-C*06, HLA-C*07:02, HLA-DRB1*11, HLA-DRB1*15, HLA-DQB1*03 and HLA-DQB1*06 (assuming either allelic or dominant genetic model). We conclude that alleles of HLA-A, -B, -C, -DRB1 and -DQB1 loci may represent potential biomarkers of COVID-19 severity and/or mortality, which needs to be confirmed in a larger set of studies.     

HLA genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.