Characterization of the novel HLA-A*24:191 allele and analysis of its MHC molecular modeling structure / 中华医学遗传学杂志

OBJECTIVE@#To characterize a novel HLA allele, A*24:191, its DNA sequence, MHC modeling structure, and the possible influence of the amino-acid residue variations on the molecule.@*METHODS@#The HLA sequence was determined by Luminex PCR-SSO and PCR-SBT. Its MHC molecular structure and the possible effects of the amino-acid residue variations were modeled and analyzed with Phyre2, RCSB PDB and HistoCheck software.@*RESULTS@#The PCR-SBT revealed the novel A*24:191 differs from A*24:02 in exon 2 at position 256, 265, 270 with G>C, G>C, A>T. The MHC molecular structure prediction showed that, compared with A*24:02, the 62nd residue of A*24:191 changed from the acidic E to a neutral Q, both with the side chain extending outside the α helix pointing forward the groove, (Risler's score, R=2), the 65th changed from the smaller neutral G extending inside the helix to a basic R with a long-chain extending upward outside the helix (R=52), and the 66th changed from the basic K to a neutral N both with a long side chain extending inside the groove (R=31). The above residues are located on the α helix of the α 1 domain which constituting the side wall of the peptide-binding groove. The DSS Score=3.85. From the surface image of the molecule, it can be clearly seen that the variations of the properties, sizes and configurations of the residues caused significant changes in the shape of the surface structure of the α helix.@*CONCLUSION@#It suggested that the residue variations are likely to change the peptide binding properties as well as the TCR and antibody binding characteristics of the molecule.

Identification of a rare platelet-specific antigen HPA-10bw allele among ethnic Han Chinese population in Shandong / 中华医学遗传学杂志

OBJECTIVE@#To study the polymorphism of human platelet antigen (HPA) system 10 among ethnic Han Chinese from Shandong, China so as to supplement the data of platelet donor bank in the region.@*METHODS@#Peripheral blood samples of platelet donors from the region were genotyped for HPA-10 alleles by PCR-sequence specific primer (PCR-SSP) and direct sequencing.@*RESULTS@#Among 1401 donors, a rare heterozygote carrier of HPA-10w (a+b+) was identified, which gave an allelic frequency of approximately 0.035%.@*CONCLUSION@#The detection of rare HPA-10bw antigen allele among ethnic Han Chinese from Shandong is useful for the diagnosis and prevention of neonatal alloimmune thrombocytopenia and post-transfusion purpura in the region.

Sequence analysis and 3D molecular structure simulation of a novel HLA allele B*51: 159 / 中华医学遗传学杂志

Objective@#To identify a novel human leukocyte antigen (HLA) B allele in a Chinese Han individual and construct its three-dimensional structure.@*Methods@#The initial HLA genotyping was performed by PCR-sequence-based typing (PCR-SBT). The ambiguous allele was confirmed with single-strand DNA sequencing. The DNA sequence was analyzed to identify the difference between the novel allele and its closest matching allele. Finally, the three-dimensional molecular structure of the novel allele was constructed using a Swiss-Model.@*Results@#One allele of the subject at the HLA-B locus was B*44: 03: 01, whilst the other was a novel allele which differed from the closest matching allele B*51: 01: 01: 01 by nucleotide (nt) 329 A>C in exon 2, resulting in an amino acid change at codon 86 (p.Asn86Thr).@*Conclusion@#A novel HLA-B allele has been identified and officially named as HLA-B*51: 159 by the WHO Nomenclature Committee for Factors of the HLA System. The three-dimensional structure of B*51: 159 was simulated.

Sequence analysis and 3D molecular structure simulation of a novel HLA allele B*51:159 / 中华医学遗传学杂志

OBJECTIVE@#To identify a novel human leukocyte antigen (HLA) B allele in a Chinese Han individual and construct its three-dimensional structure.@*METHODS@#The initial HLA genotyping was performed by PCR-sequence-based typing (PCR-SBT). The ambiguous allele was confirmed with single-strand DNA sequencing. The DNA sequence was analyzed to identify the difference between the novel allele and its closest matching allele. Finally, the three-dimensional molecular structure of the novel allele was constructed using a Swiss-Model.@*RESULTS@#One allele of the subject at the HLA-B locus was B*44:03:01, whilst the other was a novel allele which differed from the closest matching allele B*51:01:01:01 by nucleotide (nt) 329 A to C in exon 2, resulting in an amino acid change at codon 86 (p.Asn86Thr).@*CONCLUSION@#A novel HLA-B allele has been identified and officially named as HLA-B*51:159 by the WHO Nomenclature Committee for Factors of the HLA System. The three-dimensional structure of B*51:159 was simulated.

Identification of 3 novel HLA-A alleles A*24:224, A*24:225 and A*24:257 by sequence-based typing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To verify 3 novel HLA-A alleles A*24:224, A*24:225 and A*24:257 identified in Chinese Han individuals.</p><p><b>METHODS</b>No full matched results were obtained at HLA-A locus in HLA typing for China Marrow Donor Program (CMDP) using bi-allelic Sequence-Based Typing (SBT). The novel HLA alleles were identified with allele-specific amplification SBT.</p><p><b>RESULTS</b>All of the three probands had a novel nucleotide sequence at HLA-A locus. All of the 3 new sequences are most close to HLA-A*24:02:01:01 except for 1 or 2 nucleotide substitution in exon 2, which resulted in different changes in corresponding codons and encoded amino acids.</p><p><b>CONCLUSION</b>Three novel HLA-A alleles were confirmed and officially named as HLA-A*24:224, HLA-A*24:225 and HLA-A*24:257 under the GenBank accession numbers JQ899198, JQ924283 and HG003642 by the WHO Nomenclature Committee for Factors of the HLA System in November 2012 and November 2013, respectively.</p>

Confirmation of 17 rare HLA alleles and prediction of their haplotypes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To confirm 17 rare HLA alleles detected during routine HLA typing and deduce their haplotypes.</p><p><b>METHODS</b>Bi-allelic sequence-based typing and Luminex DNA PCR-SSOP assay were applied for the initial or repeat HLA typing, respectively. The rare HLA alleles were confirmed with mono-allelic sequence-based typing. Predicted haplotypes of the rare alleles were inferred based on the frequencies of HLA alleles and haplotypes in Han population.</p><p><b>RESULTS</b>The authenticity of the total 17 rare HLA alleles was proven, and 18 predicted haplotypes associated with the rare alleles were recognized. A*11:12 and DRB1*13:19 were detected twice among unrelated individuals.</p><p><b>CONCLUSION</b>Study of rare HLA alleles and predicted haplotype can provide useful information for donor searching and transplantation, and enrich polymorphisms of HLA in this population.</p>

Distribution of HLA-C alleles in Shandong Han population of China / 中华微生物学和免疫学杂志

Objective To analyze the distribution of HLA-C alleles in Shandong Han population of China.Methods One hundred and fifty unrelated potential donors,self-claimed as Han population from Shandong province,were selected from China Marrow Donor Program.Genotypes of HLA-C with the donors were identified by PCR-SBT.The frequencies of allele were calculated with direct counting method and the differences with other populations were analyzed with SPSS16.0 x2 software.Results A total of 25 alleles of HLA-C were observed and the most common alleles were C * 06:02 and C * 07:02 with the frequency of more than 10.00％.Moreover,there were 16 kinds of alleles with the frequency of more than 1.00％ accounting for 95.33％ of the total alleles.The distribution of HLA-C alleles in Shandong Han population was similar to that in northern Han population,but had some differences with that in southern Han population.In addition,the distribution of HLA-C alleles in Shandong Han population significantly differed from that of German/African American.Conclusion This study on the distribution of HLA-C alleles in Shandong Han population provides valuable references for further studies on the genetics of HLA,cross-match for organ transplantation and other genetic-associated diseases in this population.

Association of killer cell immunoglobulin-like receptor genes 2DS4 and its variant KIR1D with syphilis / 中华微生物学和免疫学杂志

Objective To investigate the killer cell immunoglobulin-like receptor (KIR) genes, KIR2DS4 and its variant KIR1D for an association with syphilis in the comparison between syphilis patients and unrelated healthy subjects. Methods One hundred and ninety syphilis patients and 192 unrelated healthy subjects were performed to determine the KIR genotypes by PCR-SSP method. The gene frequencies of KIR2DS4 and KIR1D were analyzed for an association with syphilis in the patients and healthy people who belonged to KIR gene haplotype A. Results Of 192 healthy individuals, 187 were identified with a KIR2DS4 gene. And 91 individuals were classified as homozygous haplotype A with the percent of 48.7% (91/187) in 187 KIR2DS4 positive individuals. Of 190 syphilis patients, 181 were identified with a KIR2DS4 gene. And 89 individuals were classified as homozygous haplotype A with the percent of 49.2% (89/181) in 181 KIR2DS4 positive individuals. The frequency of KIR1D/KIR1D in syphilis patients classified as haplotype A was 16.9%, and was significantly higher than that in the control group (6.6%, P=0.032). However, there was no significant difference for the frequencies of KIR2DS4/KIR2DS4 and KIR2DS4/KIR1D between the two groups (P>0.05). Conclusion KIR1D/KIR1D might be associated with syphilis in the comparison between syphilis patients and unrelated healthy controls who were classified as homozygous haplotype A.

Identification of a novel HLA allele, HLA-B*4086, and investigation of its family pedigree / 复旦学报（医学版）

Objective To identify a novel HLA allele, HLA-B*4086, in Chinese population and to investigate its pedigree. Methods An exceptional reaction pattern was detected in routine HLA typing of a CMDP (China Marrow Donor Programme) sample by PCR-sequence specific oligonucleotide primer (PCR-SSOP) assay. A new HLA-B allele was confirmed by sequence-based typing. Then family investigation was performed. Results DNA sequencing confirmed a new HLA allele. Compared with the closest macthing allele HLA-B*40060101, the novel allele has a difference at nt419 (A→T) in exon 3, which resulted in an amino acid change from Tyr to Phe at codon 140. Family investigation indicated the new allele derives from mother of the carrier. Conclusions One novel HLA allele was confirmed by sequencing based typing and it had been designated as HLA-B*4086 by the WHO Nomenclature Committee. This novel allele was inherited from mother of the carrier.