Five newly identified HLA alleles: A*0310, A*2907, B*4435, Cw*0206, Cw*0506, and confirmation of A*3106, B*3924, Cw*0314, DRB1*0322, and DRB1*1433 alleles

A number of HLA alleles have been newly identified. This concerns HLA-A*0310, A*2907, B*4435, Cw*0206, Cw*0506, of which Cw*0206 was found in three unrelated individuals, all B*4002 positive. Some other alleles are also presented but confirm earlier detected sequences: A*3106, Cw*0314, DRB1*0322, and DRB1*1433. Moreover, we identified B*3924 in a bone marrow transplant recipient and in five of six unrelated stem cell donors, selected for this patient. In all cases, B*3924 was found on a haplotype combining A*0201, B*3924, Cw*0701, and DRB1*1303. The observation of this extended haplotype is of importance for the selection for stem cell transplantation. Cells expressing B*3924 and B*4435 were typed by serology as B39 and B44, respectively. Cells expressing HLA-A*0310 do not express A3 but type as A-Blank.     

Analysis of high‐resolution HLA‐A, ‐B, ‐Cw, ‐DRB1, and ‐DQB1 alleles and haplotypes in 718 Chinese marrow donors based on donor–recipient confirmatory typings

High‐resolution human leucocyte antigen (HLA)‐A, ‐B, ‐Cw, ‐DRB1, and ‐DQB1 alleles and haplotype frequencies were analysed from 718 Chinese healthy donors selected from the Chinese Marrow Donor Program registry based on HLA donor–recipient confirmatory typings. A total of 28 HLA‐A, 61 HLA‐B, 30 HLA‐Cw, 40 HLA‐DRB1 and 18 HLA‐DQB1 alleles were identified, and HLA‐A*1101, A*2402, A*0201, B*4001, Cw*0702, Cw*0102, Cw*0304, DRB1*0901, DRB1*1501, DQB1*0301, DQB1*0303 and DQB1*0601 were found with frequencies higher than 10% in this study population. Multiple‐locus haplotype analysis by the maximum‐likelihood method revealed 45 A–B, 38 Cw–B, 47 B–DRB1, 29 DRB1–DQB1, 24 A–B–DRB1, 38 A–Cw–B, 23 A–Cw–B–DRB1, 33 Cw–B–DRB1–DQB1 and 22 A–Cw–B–DRB1–DQB1 haplotypes with frequencies >0.5%. The most common two‐, three‐, four‐ and five‐locus haplotypes in this population were: A*0207–B*4601 (7.34%), Cw*0102–B*4601 (8.71%), B*1302–DRB1*0701 (6.19%), DRB1*0901–DQB1*0303 (14.27%), A*3001–B*1302–DRB1*0701 (5.36%), A*0207–Cw*0102–B*4601 (7.06%), A*3001–Cw*0602–B*1302–DRB1*0701 (5.36%), Cw*0602–B*1302–DRB1*0701–DQB1*0202 (6.12%) and A*3001–Cw*0602–B*1302–DRB1*0701–DQB1*0202 (5.29%). Presentation of the high‐resolution alleles and haplotypes data at HLA‐A, ‐B, ‐Cw, ‐DRB1 and ‐DQB1 loci will be useful for HLA matching in transplantation as well as for other medical and anthropological applications in the Chinese population.     

HLA-A, -B, -C, -DR, -DQ typing in a population group of Senegal: distribution of HLA antigens and HLA-DRB1*13 and DRB1*11 subtyping by PCR using sequence-specific primers (PCR-SSP)

One-hundred-and sixteen Senegalese Serere were typed for HLA antigens and compared with other ethnic groups in Gambia. We did not find significant differences (Fisher's exact test; P0.01) in the HLA antigens distribution between the Serere and Mandinka groups in Senegal and the Serere, Mandinka and Wolof in The Gambia. The most common HLA haplotypes found (P0.01; Chi square with Yates' correction) were: A1, B8; A2, B51; A32, B44; A33, B58; A2, Cw2; A2, Cw4; A33, Cw3; A2, DR17; A10, DR10; B35, Cw4; B53, Cw6; B57, Cw3; B65, Cw8; B50, DR15; B52, DR4; Cw2, DR17; DR7, DQ2; DR18, DQ4. The HLA-DRB1*13 and DRB1*11 alleles were subtyped by PCR-SSP and the frequencies of these alleles in the studied population given. HLA-DRB1*1304 and DRB1102 were the most common alleles found respectively 15.0 and 18.5%     

Paroxysmal nocturnal hemoglobinuria: significant association with specific HLA-A, -B, -C, and -DR alleles in an Italian population

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the expansion of a PIG-A mutated hematopoietic stem cell. An immune-mediated origin has been suggested for this disease. Because HLA genes represent a susceptibility factor for autoimmunity, we investigated HLA genotype in 42 Italian PNH patients compared with 301 control subjects of the same ethnic origin. A significantly increased frequency of the HLA class I alleles A*0201 (p < 0.05), B*1402 (p < 0.001), and Cw*0802 (p < 0.005), and of the HLA class II DRB1*1501 (p < 0.01) with the linked DQB1*0602 (p ≤ 0.05) and DRB1*01 (p ≤ 0.05) with the linked DQB1*0501 (p ≤ 0.01) alleles, has been observed. Notably, a fourfold increase of the haplotype B*1402, Cw*0802 (p < 0.0005) and a 15-fold increase of the Mediterranean haplotype A*33, B*1402, Cw*0802, DRB1*0102, DQB1*0501 (p < 0.005) was also revealed. This association may provide new insights into the autoimmune pathogenesis of PNH.     

The HLA system in the population of Mongolia

The frequencies of HLA-A, B, C and DRB1 alleles and haplotype frequencies for HLA-A, B, C and A, B, DR loci were studied in 201 healthy unrelated Khalkha-Mongolians. The most common class I antigens were A24 (25.8%), A2 (23.4%), B61 (12.6%), B51 (8.5%), Cw10 (14.2%), Cw9 (14.1%), Cw7 (13.3%), Cwl (11.8%) and Cw6 (10.2%). A total of 35 DRB1 alleles were identified in this group of samples. The most frequent DRB1 allele was DRB1*0301 (11.1%), followed by DRB 1*0701 (9.7%) and DRBl*H01 (8.5%). One novel DRB1 allele (14MV) and three rare types, DRB1*1111, DRB 1*1504 and DRB 1*1412, recently described in Jews, the Dai minority of China and Japanese, respectively, were identified in Mongolians. The phylo-genetic tree constructed by UPG method put Mongolians in the Northeast Asian cluster. A comparison of three locus haplotype distributions with world populations, revealed that Mongolians share several characteristics in common with other Mongoloids as well as with Caucasoids and Amerindians. The most common A, B and DR haplotype in Mongolians, A33-B58-DR3, was shared with Thai, Thai Chinese and Singapore Chinese. These data support that unique genetic background of Mongolians played a major role in ethnic formation and differentiation of Mongoloid populations.     

HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies distinguish Eastern European Americans from the general European American population

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 558 consecutively recruited US volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of 31 HLA-A alleles, 29 HLA-C alleles, 59 HLA-B alleles, and 42 HLA-DRB1 alleles identified (A*0325, B*440204, Cw*0332, and *0732N) are novel. The HLA-A*02010101g allele was observed at a frequency of 0.28. Two-, three-, and four-locus haplotypes were estimated using the expectation-maximization algorithm. The highest frequency extended haplotypes (A*010101g–Cw*070101g–B*0801g–DRB1*0301 and A*03010101g–Cw*0702–B*0702–DRB1*1501) were observed at frequencies of 0.04 and 0.03, respectively. Linkage disequilibrium values (     ) of the constituent two-locus haplotypes were highly significant for both extended haplotypes ( P values were less than 8 × 10⁻¹⁰) but were consistently higher for the more frequent haplotype. Balancing selection was inferred to be acting on all the four loci, with the strongest evidence of balancing selection observed for the HLA-C locus. Comparisons of the A–C–B haplotypes and DRB1 frequencies in this population with those for African, European, and western Asian populations showed high degrees of identity with Czech, Polish, and Slovenian populations and significant differences from the general European American population.     

Immunogenetics of two new HLA alleles: A*0108 and B*4031

Two new alleles, HLA-A*0108 and B*4031, were identified in north-western European Caucasoid subjects. A*0108 differed from A*010101 by a single substitution (C to T) at position 216 in exon 3, resulting in an amino acid difference of Arg to Trp at position 163. It was present on a haplotype with B*1501/60/70/71; Cw*0303; DRB1*1301; DRB3*0202; DQA1*0103; DQB1*0603 and its product reacted as a normal HLA-A1 specificity. B*4031 differed from B*4001 by two nucleotides in exon 3 (positions 20 (G to C) and 69 (A to G)) resulting in two amino acid differences (Arg to Ser at position 97 and Asn to Asp at position 114). It was found on a haplotype with HLA-A*03; Cw*0304; DRB1*0404/32; DRB4*0101/3/5; DQA1*03; DQB1*0302 and has the HLA-B60 specificity. Both alleles have frequencies of < 0.0002 in the largely north-western European Caucasoid blood donor population resident in Wales.     

中国汉族人群供-受者HLA-A、B、Cw、DRB1和DQB1高分辨等位基因频率分布及错配比例的研究

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.

Abstract：

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.     

A new pair of HLA-C alleles, Cw* 12042 and Cw*1203, differing at the KIR-related dimorphism of codons 77–80

Abstract: A previously unknown HLA-C variant of the Cw*12 group was identified by PCR-SSP from genomic DNA of cell NDS-JD. Molecular cloning and nucleotide sequence analysis permitted the characterization of the complete coding region of this new allele, Cw*12042. The new variant differs from the recently reported Cw*12041 by two silent changes at exons 2 and 3, and from Cw*1203 by coding changes at codons 77 and 80. Cw*1203 (Ser-Asn) and Cw*12042 (Asn-Lys) constitute the second known example of HLA-C alleles only differing at the KIR-related dimorphism of residues 77–80. The new allele is associated in cell NDS-JD with the haplotype HLA-A*2403, Cw*12042, B*51, DRB1*1502, DRB5*0102, DQB1*0601, possibly related from the evolutionary aspect to the ancestral haplotype A*2402, Cw*1202, B*5201, DRB1*1502, DRB5*0102, DQBl*0601.     

HLA alleles and haplotypes in French North African immigrants

Human leukocyte antigen (HLA) haplotypes (n = 187) were genotyped and assigned by the mode of inheritance in migrant families from North Africa who reside in the Paris, France, area. The distribution of alleles and haplotypes in that population was compared with the one obtained in a control population of ancient French natives residing in the same area (248 independent haplotypes also assigned by the mode of inheritance were studied). The results in migrants reveal the following: (1) a higher diversity in the distribution of HLA-A and -DRB1 alleles; (2) lower frequencies of alleles common in our region, such as A*0201 B*1501, B*4001, and DRB1*0401 and increased frequencies of minor subtypes, such as A*3002 and DRB1*0402; and (3) distinct distributions of B/Cw, DRB1/DQB1 or B/Cw/DRB1/DQB1 haplotypes. The results also revealed that the four most frequent five-allele haplotypes in controls i.e., HLA-A*0101/B*0801/Cw*0701/DRB1*0301/DQB1*0201; A*0301/B*0702/Cw*0702/DRB1*1501/DQB1*0602 (both of Indo-Celtic origin); A*2902/B*4403/Cw*1601/DRB1*0701/DQB1*0202 (frequent in Western-Europeans); and A*0201/B*1501/Cw*0304/DRB1*0401/DQB1*0302, represent 10.5% of the total haplotypes in controls but 1.6% in North Africans. Conversely, 9 five-allele haplotypes in multiple copy in North Africans (among which A*3002/B*1801/Cw*0501/DRB1*0301/DQB1*0201 of Paleo-North African origin and A*0201/B*0702/Cw*0702/DRB1*1501/DQB1*0602 of ancient European and Paleo-North African origin) represent 9.6% of the total haplotypes in North Africans but 2.4% in controls. These results thus suggest a low degree of admixture between the two populations.     

Nucleotide sequence of the corrected DQB1*06011 allele

The DQB1*06011 allele first classified and registered with the codon ACC at position 51(1) was recently corrected to ACG by Dr. Akinori Kimura (2) and in independently confirmed in our laboratory (3). The correct nucleotide sequence for this allele is shown below. The DQB1*06011 allele was found in two sisters of Turkish nationality who had been serologically typed for class I as HLA-A11, A33, B44, B52, Cw4. Nucleotide sequencing based typing of HLA class II alleles disclosed DRB1*0701, *15021, DRB4*01011/*0103, DRB5*0102, DQA1*0103, *0201, DQB1*02, *06011, DPB1*0401,*11011.     

Immunogenetic study of a new HLA allele,B*2723

A novel HLA-B*27 allele (B*2723) detected by irregular serological and PCR-SSP typing results was identified by nucleotide sequencing of exons 2 and 3. B*2723 differs from B*27052 by nine nucleotides which encode seven amino acid changes at positions 63 (Glu to Asn), 67 (Cys to Phe), 69 (Ala to Thr), 70 (Lys to Asn), 71 (Ala to Thr), 74 (Asp to Tyr) and 77 (Asp to Ser) in the alpha1 helix. All these substitutions are possessed by B*35 alleles suggesting that B*2723 was created by a gene conversion-like event involving B*27052 and a B*35 allele. Using the HLA-A*26 and DRB1*12 alleles of the B*2723-bearing haplotype as 'markers', two further examples of B*2723 were found in 29,851 blood donors. Therefore, B*2723 has a 'minimum' gene frequency of 0.000034 (phenotype frequency 0.0067%) in blood donors resident in Wales. In all three families, B*2723 was present on a haplotype with: A*26; Cw*0202; DRB1*1201/6/7; DRB3*02; DQA1*05; DQB1*0301. The B*2723 product failed to react with HLA-B27 antisera and reacted weakly or not at all with Bw4 antisera. Lack of the ECAKA motif at amino acid positions 63, 67, 69-71 probably accounts for lack of the B27 specificity while the amino acid combination 74Y, 77S, 80T, 81L may cause aberrant Bw4 reactivity.     

Distribution of HLA-A, -B, -Cw, and -DRB1 alleles and haplotypes in an isolated Han population in Southwest China

In this study, polymorphisms of human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1) loci were analyzed in an isolated Han population living in Fengyandong in the Yunnan province of Southwest China (FYDH) using a high-resolution polymerase chain reaction–Luminex typing method. A total of 13 A, 26 B, 15 Cw, and 23 DRB1 alleles of HLA were found in FYDH. The frequencies of A*1101, A*0207, A*2402, B*4601, B*1502, Cw*0102, Cw*0801, DRB1*0901, and DRB1*1202 were >10%. The following haplotypes were common with frequencies >5%: three A-B, four Cw-B, two B-DRB1, two A-B-DRB1, three A-B-Cw, two B-Cw-DRB1, and two A-B-Cw-DRB1 phylogenetic tree and multidimensional scaling analysis based on HLA-A, -B, and -DRB1 allele frequencies of 18 Han populations suggested that FYDH was an isolated Han population, but the analytic result also provided a suggestion that FYDH was genetically related to Chinese Southern Han. According to the characteristics of the HLA allele and haplotype distributions and significantly reduced allelic and haplotypic diversity in FYDH, we deduced that genetic drift and/or selection and subsequent geographic isolation had influenced the distribution characteristics of the HLA gene in FYDH. In addition, significantly reduced allelic and haplotypic diversity in FYDH makes it an ideal homogenous population and very useful model for future investigations of issues related to immunogenetic diseases in the Han population.     

Sequence of a new DR12 allele with two silent mutations that affect PCR-SSP typing

A new HLA-DR12 allele has been identified in a European Caucasoid bone marrow donor. The DRB1*12012 allele differs from DRB1*12011 by two silent substitutions at codons 72 and 78, two polymorphic positions used for DNA subtyping of the DR12 serotype. The co-occurence of the two nucleotide changes is unique to the DR12 group and results in a new PCR-SSP typing pattern. The complete HLA type of the donor is A24, A68; B55, B61; Cw*01, Cw*0304; DRB1*12012, DRB1*1402; DRB3*0101, DRB3*0202; DQB1*0301. HLA-DRB1*12012 is a rare allele as it occurs in < 0.2% of DR12 donors.     

HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in the Kinh population in Vietnam

Allele and haplotype frequencies of the human leukocyte antigens (HLA) were studied in the Kinh Vietnamese population. We analyzed 170 unrelated healthy individuals. DNA-based HLA typing was performed using a microsphere-based array genotyping platform with sequence-specific oligonucleotide probes to distinguish HLA-A, -B, -C, -DRB1 and -DQB1 alleles. A total of 21 HLA-A, 37 HLA-B, 18 HLA-C, 25 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. HLA-A*1101, A*2402, A*3303, B*1502, B*4601, Cw*0102, Cw*0702, Cw*0801, DRB1*1202, DQB1*0301, DQB1*0303, and DQB1*0501 were found with frequencies higher than 10%. Two representative haplotypes bearing two to five HLA loci were A*1101-B*1502 and A*3303-B*5801 for HLA-A-B; Cw*0801-B*1502 and Cw*0102-B*4601 for HLA-C-B; B*1502-DRB1*1202 and B*4601-DRB1*0901 for HLA-B-DRB1; DRB1*1202-DQB1*0301 and DRB1*0901-DQB1*0303 for HLA-DRB1-DQB1; A*1101-Cw*0801-B*1502 and A*3303-Cw*0302-B*5801 for HLA-A-C-B; A*1101-B*1502-DRB1*1202 and A*2901-B*0705-DRB1*1001 for HLA-A-B-DRB1, A*1101-Cw*0801-B*1502-DRB1*1202-DQB1*0301 and A*2901-Cw*1505-B*0705-DRB1*1001-DQB1*0501 for HLA-A-C-B-DRB1-DQB1. Allele distribution and haplotype analysis demonstrated that the Vietnamese population shares HLA patterns with southern Chinese, Thai, Javanese and Micronesians, while it also retains unique characteristics.     

Sequence, genetics and serology of a new HLA-B allele: B*4903

A new HLA-B allele - B*4903 - was detected by the polymerase chain reaction using sequence-specific priming (PCR-SSP), in a Caucasoid bone marrow panel donor, that differs from B*4901 by 8 nucleotides at positions 141, 142, 144, 165, 167, 193, 206 and 213 in exon 2. These substitutions all occur in HLA-B*51 and B*52 alleles and encode 4 amino acid substitutions at positions 24 (Thr to Ala), 32 (Leu to Gln), 41 (Thr to Ala) and 45 (Lys to Thr). This suggests that B*4903 occurred following a gene conversion-like event involving B*4901 and probably a B*51 allele. HLA-B*4903 was identified on a haplotype with: HLA-A*0201; Cw*07; DRB1*1302/34; DRB3*0301; DQA1*0102; DQB1*0604; BfS; C4A3; C4BQ0 and encodes a unique serological specificity which was characterised by the reactivity of 55 antisera directed towards at least four predicted epitopes. No further examples of B*4903 were found in 15,796 consecutive HLA PCR-SSP typed donors from the Welsh Bone Marrow Donor Registry, indicating that this allele has a phenotype frequency of <0.01% and a gene frequency of <0.00004.     

The distribution of human leukocyte antigen-A, -B,and -DRB1 alleles and haplotypes based on high-resolution genotyping of 167 families from Jiangsu Province,China

We investigated the human leukocyte antigen (HLA)-A, -B, and -DRB1 allele frequencies, the A–B–DRB1, A–B, B–DRB1, and A–DRB1 haplotype frequencies, and the characteristics of linkage disequilibrium between 2 loci in high resolution based on 167 unrelated families from Jiangsu Province, China. A total of 26 alleles at the A locus, 55 alleles at the B locus, and 34 alleles at the DRB1 locus were reported in this study. The top 5 most frequent HLA alleles at the HLA-A, -B, and -DRB1 loci, respectively, were A*11:01, A*24:02, A*02:01, A*33:03, A*30:01; B*13:02, B*40:01 B*46:01, B*58:01, B*54:01; DRB1*09:01, DRB1*07:01, DRB1*12:02, DRB1*15:01, and DRB1*08:03. Several haplotypes with high frequencies were deduced in this study. The top 3 most common A–B–DRB1 haplotypes observed were A*30:01–B*13:02–DRB1*07:01, A*33:03–B*58:01–DRB1*03:01, and A*02:07–B*46:01–DRB1*09:01. The top 3 most common A–B haplotypes were A*30:01–B*13:02, A*33:03–B*58:01, and A*02:07–B*46:01. The top 4 most common A–DRB1 haplotypes were A*30:01–DRB1*07:01, A*33:03–DRB1*13:02, A*24:02–DRB1*09:01, and A*33:03–DRB1*03:01. Finally, the top 3 most common B–DRB1 haplotypes were B*13:02–DRB1*07:01, B*46:01–DRB1*09:01, and B*58:01–DRB1*03:01. From the linkage disequilibrium calculation, the most prominent associations were A*30:01–B*13:02, B*13:02–DRB1*07:01, and A*01:03–DRB1*01:02. These allele and haplotype frequencies could be useful for finding the best matched donors for patients in the China Marrow Donor Program Jiangsu Branch.     

HLA-DRB1*0826 and HLA-DQB1*0627, two novel class II alleles identified in blood stem cell donors of Caucasian origin

This report describes two novel HLA class II alleles, HLA-DRB1*0826 and HLA-DQB1*0627, that have been identified in two unrelated voluntary blood stem cell donors of Caucasian origin. HLA-DRB1*0826 is characterized by a nucleotide substitution (G to T) in exon 2 at position 163, leading to an amino acid exchange from argenine to leucine. The donor phenotype is HLA-A*0301,*2902; B*3501,*4403; Cw*0401,*1601; DRB1*0101,*0826; DQB1*0402, *0501. The HLA-DQB1*0627 alleles contain a nucleotide substitution at position 184 (T to C) resulting in an amino acid exchange from tyrosine to histidine. Family segregation analysis revealed that the HLA-DQB1*0627 allele belongs to the haplotype A*0101, B*1517, Cw*0701, DRB1*1302, DQB1*0627. The donor phenotype is HLA-A*0101; B*0801,*1517; Cw*0701; DRB1*1302,*1501; DQB1*0602,*0627.     

Human leukocyte antigen-A, -B, and -Cw polymorphism in a Berber population from North Morocco using sequence-based typing

Class I human leukocyte antigen (HLA) polymorphism was examined in a Berber population from North Morocco, named Metalsa (ME). All data were obtained at high-resolution level, using sequence-based typing. The most frequent alleles were: HLA-A*0201 and A*0101; HLA-B*44 (B*4403 and B*4402); B*0801 and the B*50 allele group (B*5001 and B*5002); HLA-Cw*0602; and Cw*07 group (Cw*070101, Cw*070102, Cw*0702, Cw*0704, and Cw*0706), and Cw*040101. The novel HLA-B*570302 allele was identified. It differs at position 486 and position 855 from B*570301, resulting in synonymous Thr and Val. The analysis also evidenced some alleles common in Africans (A*3402, A*6802, A*7401, B*1503, B*4102, B*4202, B*7801, B*5802, Cw*1701, and Cw*1703) and some uncommon alleles (A*3004, B*2702, B*2703, B*5001,02, B*3503, and Cw*0706). The predominant HLA-A-Cw-B-DRB1-extended haplotypes in ME population were A*0101-Cw*0501-B*4402-DRB1*0402, A*240201-Cw*0701-B*0801-DRB1*030101, A*2301-Cw*040101-B*4403-DRB1*040501, A*0201-Cw*040101-B*4403-DRB1*1302, and A*3002-Cw*0602-B*5002-DRB1*0406. This study demonstrates a strong relatedness of ME to other Moroccan and North African populations, some characteristics of sub-Saharan Africans and evidenced the influence of various immigrations during centuries. Nevertheless, this study highlights some unique genetic traits of the ME population compared to other ethnic groups within Morocco, which could be of great interest for clinical aims, transplantation, and diseases.