Identification of a novel HLA-DRB1 allele, DRB1*11:95

The DRB1*11:95 showed a single nucleotide difference with the DRB1*11:01:01 allele at codon 10 (TAC/TGC).     

Identification of a novel HLA-DRB1*12 allele, DRB1*1218, in Chinese population

Here, we report the identification of a novel human leukocyte antigen-DRB1*12 variant, DRB1*1218 allele, in a Chinese Han individual. The novel DRB1*12 variant allele differed from the closest allele DRB1*120201 by nucleotide 262 G>C (codon 59 GAG>CAG) missense mutation in exon 2, which resulted in an amino acid substitution of Glu>Gln.     

Identification and characterization of a novel HLA-DRB1 allele, DRB1*0830*

Here, we report on the identification and characterization of a novel human leukocyte antigen (HLA) DRB1 allele, DRB1*0830. This allele was identified in a candidate for hematopoietic stem cell donation. While the DNA sequence of HLA-DRB1*0830 most closely matches to DRB1*080202, its amino acid sequence resembles DRB1*080202 and DRB1*0813. Due to a substitution at nucleotide position 286 HLA-typing using sequence-specific oligonucleotide hybridization or amplification using sequence-specific primers gave inconclusive results. Allele-specific DNA sequencing confirmed a 286 T-->A substitution resulting in Phe67Ile.     

Identification of a novel HLA-DRB1 allele,DRB1*0108, by sequence-based DRB typing in two siblings

We report here a novel DRB1 allele identified during sequence-based HLA-DRB typing. This allele was detected during routine HLA typing of a patient and his family prior to bone marrow transplantation. The new allele, DRB1*0108, was found in the patient and in a brother. Molecular cloning and sequencing confirmed that the new DRB1 allele is identical to DRB1*0101 at exon 2 except for a single nucleotide substitution at codon 37 (TauCC-->TauAlphaC), changing the encoded serine to tyrosine. This position of the beta1 domain lies in the floor of the antigen-binding groove and shows the highest polymorphism among DRB1 alleles.     

Ten novel HLA-DRB1 alleles and one novel DRB3 allele

Ten novel HLA-DRB1 and one DRB3 alleles are described. Eight of the variants are single-nucleotide substitutions, four resulting in an amino acid change (DRB1*1145, *1148, *0828 and *1514) and four with silent substitutions (DRB1*040504, *130103, *160502 and DRB3*020204). Two alleles differ by two nucleotide changes altering one (DRB1*1447 and *1361) amino acid and one allele alters three nucleotides and two amino acids.     

Description of a novel HLA-DRB1 allele,DRB1*1207

A new DRB1 allele has been identified during routine HLA-DRB1 generic typing with sequence specific oligonucleotides. The new allele was confirmed by PCR-restriction fragment length polymorphism analysis and subsequently sequenced. This showed the novel allele, named HLA-DRB1*1207, was similar in sequence to DRB1*12011, except for codon 69 of exon 2.     

A novel HLA-DRB1 allele,DRB1*0707

We report herein the identification of a new HLA-DRB1 allele, DRB1*0707. This new allele was seen in a volunteer bone marrow donor (ID#118069) belonging to the German bone marrow donor registry (DKMS). HLA-DRB1*0707 was detected while performing HLA-DRB1 high resolution typing by sequence based typing. This novel allele differs from DRB1*070101 by a single nucleotide substitution at position 163 (C-->T) in exon 2.     

A novel HLA-DRB1 allele, DRB*090202, is identified in a Taiwanese family

Human leukocyte antigen-DRB1*090202 has two synonymous nucleotide substitutions with DRB1*090201 at codons 57 and 58, which may be the result of a gene conversion.     

A novel HLA-DRB1 allele, DRB1*1219, was identified by sequence-based typing in a Chinese leukaemia family

A novel human leukocyte antigen DRB1 allele, DRB1*1219, has been identified in a Chinese leukaemia patient and his family by polymerase chain reaction sequence-based typing, which has one nucleotide change at position 341 (C→T) in exon 2 from the closest matching allele DRB1*120201, resulting in an amino acid substitution from Ala→Val at codon 85.     

新的HLA-DRB1等位基因DRB1*1212的核苷酸序列分析

目的验证一个新的HLA等位基因HLA—DRB1＊1212的序列。方法采用盐析法抽提样本基因组DNA，利用HLA—DRB1组特异性引物PCR扩增先证者HLA—DRB1等位基因的第2外显子，PCR产物经割胶回收后进行测序分析，通过聚合酶链反应-序列特异性寡核苷酸探针方法验证测序发现突变点。结果先证者有两个HLA—DRB1等位基因，其中一个为HLA—DRB1＊090102，另一个HLA—DRB1等位基因，经BLAST验证为新的等位基因，新的等位基因序列已递交GenBank（AY899825）。与最接近的DRB1＊120101等位基因序列相比，新的等位基因仅在第2外显子上有1个核苷酸不同，即第199位A→C，导致第67位氨基酸Ile—Leu。结论该等化基因为新的HLA—DRB1等位基因，被世界卫生组织HLA因子命名委员会正式命名为HLA-DRB1＊1212。     

A novel HLA-DRB1 allele, DRB1*112802, was identified in a Chinese individual

We report here a novel human leukocyte antigen-DRB1 allele, DRB1*112802, which was identified from a Chinese individual during sequence-based typing. The new allele is identical to DRB1*112801 except for one nucleotide change at nucleotide 189 (A → G ), codon 34 Q (CAA) → Q (CAG), no coding change.     

HLA-DRB1*1218新等位基因克隆测序鉴定及内含子序列分析

Objective To identify a novel human leukocyte antigen (HLA) allele by cloning and sequence-based typing in Chinese population, and analyzing the sequence of the introns 1 and 2. Methods The routine HLA-A, -B, -DRB1 low resolution genotyping for stem cell donor from Guangdong province was performed with polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). An unknown HLA-DRB1 allele was initially detected by HLA typing. Genomic DNA of the proband was amplified by using HLA-DRB1 locus group-specific primer, the amplified product was cloned, sequenced, and compared to the closest DRB1 * 120201 allele and the closest intron sequence of the DRB1 * 030101 allele. Results The sequencing results showed that a normal DRB1 * 080302 and a novel DRB1 * 1218 variant allele were identified. The sequence of the novel allele has been submitted to GenBank (FJ481086). The novel allele had 1 nucleotide substitution of the closest matching allele HLA-DRB1 * 120201 at nt262(G →C) in exon 2, resulting in an amino acid change from GIu(GAG)→Gln (CAG) at codon 59. The intron 2 sequence is identical between the novel HLA-DRB1 * 1218 and DRB1 * 030101, but there are 12 nucleotides substitution in intron 1. Conclusion A novel HLA allele was confirmed by cloning and sequence-based typing in Chinese. It was officially designated as HLA-DRB1 * 1218 by WHO Nomenclature Committee.     

HLA-DRB1*1218新等位基因克隆测序鉴定及内含子序列分析

Objective To identify a novel human leukocyte antigen (HLA) allele by cloning and sequence-based typing in Chinese population, and analyzing the sequence of the introns 1 and 2. Methods The routine HLA-A, -B, -DRB1 low resolution genotyping for stem cell donor from Guangdong province was performed with polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). An unknown HLA-DRB1 allele was initially detected by HLA typing. Genomic DNA of the proband was amplified by using HLA-DRB1 locus group-specific primer, the amplified product was cloned, sequenced, and compared to the closest DRB1 * 120201 allele and the closest intron sequence of the DRB1 * 030101 allele. Results The sequencing results showed that a normal DRB1 * 080302 and a novel DRB1 * 1218 variant allele were identified. The sequence of the novel allele has been submitted to GenBank (FJ481086). The novel allele had 1 nucleotide substitution of the closest matching allele HLA-DRB1 * 120201 at nt262(G →C) in exon 2, resulting in an amino acid change from GIu(GAG)→Gln (CAG) at codon 59. The intron 2 sequence is identical between the novel HLA-DRB1 * 1218 and DRB1 * 030101, but there are 12 nucleotides substitution in intron 1. Conclusion A novel HLA allele was confirmed by cloning and sequence-based typing in Chinese. It was officially designated as HLA-DRB1 * 1218 by WHO Nomenclature Committee.     

人类白细胞抗原新等位基因DRB1*1219的确认及其序列分析

目的 鉴定分析1个白血病患者家庭HLA-DRB1位点1个新等位基因.方法 应用PCR-序列特异性引物及Luminex DNA杂交流式分型技术进行HLA分型,发现1个与HLA-DRB1*120201相关的未知基因.应用DNA测序技术进行鉴定分析并与已知序列比对分析.结果 先证者DRB1位点有1个等位基因的核苷酸序列与所有已知基因序列均不相同,与同源性最高的DRB1*120201相比,第2外显子第341位核苷酸碱基发生了C→T,结果导致相应85位密码子编码的丙氨酸变为缬氨酸.结论 测序表明被测样本含有1个HLA-DRB1新等位基因,被世界卫生组织HLA因子命名委员会正式命名为HLA-DRB1*1219(序列号EJ374889).

Abstract：

Objective To identify a novel HLA DRB1 allele in a Chinese leukemia family. Methods A new HLA-DRB1 allele was initially detected by polymerase chain reaction-sequence specific primer and unusual reaction pattern by Luminex RSSO, then DNA sequencing was performed to identify the sequence of the novel allele. Results The DNA sequencing revealed the presence of the new allele which differs from the closest macthing HLA- DRB1 * 120201 by a single nucleotide substitution at position (341 C→T in exon 2),resulting in an amino acid change from Ala to Val at coden 85. Conclusion A novel allele was confirmed by DNA sequencing and has been designated HLA-DRB1 * 1219 by the WHO Nomenclature Committee.     

HLA-DRB1*1218新等位基因克隆测序鉴定及内含子序列分析

Objective To identify a novel human leukocyte antigen (HLA) allele by cloning and sequence-based typing in Chinese population, and analyzing the sequence of the introns 1 and 2. Methods The routine HLA-A, -B, -DRB1 low resolution genotyping for stem cell donor from Guangdong province was performed with polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). An unknown HLA-DRB1 allele was initially detected by HLA typing. Genomic DNA of the proband was amplified by using HLA-DRB1 locus group-specific primer, the amplified product was cloned, sequenced, and compared to the closest DRB1 * 120201 allele and the closest intron sequence of the DRB1 * 030101 allele. Results The sequencing results showed that a normal DRB1 * 080302 and a novel DRB1 * 1218 variant allele were identified. The sequence of the novel allele has been submitted to GenBank (FJ481086). The novel allele had 1 nucleotide substitution of the closest matching allele HLA-DRB1 * 120201 at nt262(G →C) in exon 2, resulting in an amino acid change from GIu(GAG)→Gln (CAG) at codon 59. The intron 2 sequence is identical between the novel HLA-DRB1 * 1218 and DRB1 * 030101, but there are 12 nucleotides substitution in intron 1. Conclusion A novel HLA allele was confirmed by cloning and sequence-based typing in Chinese. It was officially designated as HLA-DRB1 * 1218 by WHO Nomenclature Committee.     

HLA-DRB1*1218新等位基因克隆测序鉴定及内含子序列分析

目的 鉴定中国人群人类白细胞抗原(human leukocyte antigen,HLA)DRB1基因,分析新等位基因第1和2内含子序列信息.方法 采用聚合酶链反应-序列特异寡核苷酸探针反向杂交法(polymerase chain reaction-sequence specific oligonucleotide probes,PCR-SSOP)对广东地区随机正常人群进行HLA常规基因分型,发现1个与HLA-DRB1*120201相近的未知基因,对先证者DNA应用组特异性引物扩增HLA-DRB1位点第2外显子,PCR产物经克隆到质粒载体中以获得单链,对克隆所得产物进行HLA-DRB1基因的第2外显子及第1和第2内含子双向测序分析.并与DRB1*120201基因序列的第2外显子和DRB1*03010101等位基因内含子相比较.结果 发现该个体的一个HLA-DRB1*080302基因被确认,而另一个HLA-DRB1基因为新等位基因,其序列被GenBank接受(编号为FJ481086).新等位基因与最相近的DRB1*120201相比,在第2外显子上有1个核苷酸的不同,即第262位G→C(密码子59 GAG→CAG,氨基酸59 Glu→Gln).DRB1*1218与DRB1*03010101等位基因第2内含子序列完全相同,而与DRB1*03010101等位基因第1内含子序列相比较有12个碱基不同.结论 发现并鉴定一个新的HLA等位基因,经世界卫生组织HLA因子命名委员会正式命名为HLA-DRB1*1218.     

HLA-DRB1*1218新等位基因克隆测序鉴定及内含子序列分析

Objective To identify a novel human leukocyte antigen (HLA) allele by cloning and sequence-based typing in Chinese population, and analyzing the sequence of the introns 1 and 2. Methods The routine HLA-A, -B, -DRB1 low resolution genotyping for stem cell donor from Guangdong province was performed with polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). An unknown HLA-DRB1 allele was initially detected by HLA typing. Genomic DNA of the proband was amplified by using HLA-DRB1 locus group-specific primer, the amplified product was cloned, sequenced, and compared to the closest DRB1 * 120201 allele and the closest intron sequence of the DRB1 * 030101 allele. Results The sequencing results showed that a normal DRB1 * 080302 and a novel DRB1 * 1218 variant allele were identified. The sequence of the novel allele has been submitted to GenBank (FJ481086). The novel allele had 1 nucleotide substitution of the closest matching allele HLA-DRB1 * 120201 at nt262(G →C) in exon 2, resulting in an amino acid change from GIu(GAG)→Gln (CAG) at codon 59. The intron 2 sequence is identical between the novel HLA-DRB1 * 1218 and DRB1 * 030101, but there are 12 nucleotides substitution in intron 1. Conclusion A novel HLA allele was confirmed by cloning and sequence-based typing in Chinese. It was officially designated as HLA-DRB1 * 1218 by WHO Nomenclature Committee.     

Identification of a new HLA-DRB1*04 allele, DRB1*0437

In this report we describe the identification of a novel DRB1*04 allele, DRB1*0437, found in a Spanish individual. The routine HLA typing, in the context of bone marrow transplantation, by polymerase chain reaction-sequence-based typing (PCR-SBT) made possible the identification of this new allele. This allele is identical to DRB1*0402 except for a single nucleotide substitution at position 286 (A-->C), changing the encoded Isoleucine to a Leucine. The DRB1*0437 allele conserves the same two acidic residues at codons 70 and 71 that confer to DRB1*0402 its association to some autoimmune diseases.