[Study on HLA nucleotide sequence matching in epitope positions among recipient-donor pairs for allogenic hematopoietic stem-cell transplantation].

OBJECTIVE: To analyze the human leukocyte antigens(HLA)-A, -B, -Cw, -DRB1 and DQB1 nucleotide sequences between patients waiting for allogenic hematopoietic stem-cell transplantation (HSCT) and donors in Chinese population, and to establish strategy for maximizing optimal donor selection. METHODS: HLA high-resolution typing in a total of 537 recipient-donor pairs was determined by sequence based typing (SBT) method. The nucleotide BLAST tool was used to compare the nucleotide sequences among recipient-donor pairs. RESULTS: Only 16.20% (88/537) of recipient-donor pairs were found to fully match for nucleotide sequences of all HLA-A,-B,-Cw, -DRB1 and -DQB1 loci. Mismatch rate in single locus were 8.38% in HLA-A, 0.74% in HLA-B, 12.29% in HLA-C, 2.42% in HLA-DRB1, and 2.79% in HLA-DQB1, respectively. Mismatch rate in two or multiple HLA loci was 42.65%. Nonpermissive allele mismatch combinations (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) were detected in single mismatch HLA locus of recipient-donor pairs, mismatches of B 07:05:01-B 07:06, Cw 07:01:01-Cw 07:06 combinations outside of epitope positions were detected in two recipient-donor pairs. CONCLUSION: Our data suggested that attention should be paid in comparing nucleotide sequences between recipient and donor, and in distinguishing nucleotide sequence mismatches within and outside of the epitope positions. These results could serve as guidelines for donor selection.

[Analysis on haplotypes of five HLA loci in southern Chinese Han population by sequence-based typing].

OBJECTIVE: To analyze the polymorphism and haplotypes of HLA-A, B, Cw, DRB1 and DQB1 loci in Chinese Han population. METHODS: A total of 186 unrelated healthy individuals from southern China were analyzed by sequence-based typing. Two-, three-, and five-locus haplotypes were estimated using the Expectation Maximization Algorithm. RESULTST: Twenty-eight alleles for the HLA-A locus, 49 HLA-B alleles, 24 HLA-C alleles, 29 HLA-DRB1 alleles and 20 HLA-DQB1 alleles were detected. The A*0207-B*4601(10.81%), A*3303-B*5801(6.14%), B*4601-DRB1*0901(6.22%), B*4001*-DRB1*0901(3.78%), DRB1*090-DQB1*0303 (12.16%) and DRB1*1202-DQB1*0301(8.38%), A*0207-B*4601-Cw*0102 (10.75%), A*3303-B*5801-Cw*0302 (5.14%), A*0207-B*4601-DR*0901(5.07%), A*3303-B*5801-DRB1*0301(2.96%), A*0207-B*4601-Cw*0102-DRB1*0901-DQB1*0303(4.87%) and A*1101-B*1301-Cw*0304-DRB1*1501-DQB1*0601(2.43%) were the most common haplotypes in the southern Chinese Han population. CONCLUSION: The results have shown the characteristics of the five HLA loci haplotype distribution and provided more information in anthropology, disease association studies and transplantation.

[Analysis of HLA haplotype frequency and linkage disequilibrium in patients with acute lymphoblastic leukemia from Northern Chinese Han].

OBJECTIVE: To analyze the difference between the frequencies of HLA-A-B, B-DRB1 and A-B-DRB1 haplotype, as well as their linkage disequilibrium pattern in patients with acute lymphoblastic leukemia(ALL) and healthy controls from Northern Chinese Han. METHODS: The frequencies of HLA-A-B, B-DRB1, A-B-DR haplotypes and linkage disequilibrium were estimated by Expectation Maximization method based on the genotypes of 643 patients with ALL and 2 0359 unrelated healthy donors, and the statistical significance between the two groups were estimated by chi-square test. Linkage disequilibrium was analyzed with population genetic methods. RESULTS: The most common HLA-A-B, B-DRB1, and A-B-DR haplotypes were A30-B13, A2-B46, A33-B58, B13-DR7, B46-DR9, B52-DR15, B58-DR17, A30-B13-DR7, A33-B58-DR17 and A1-B37-DR10 in both groups. The frequencies of A30-B13, A2-B46, A33-B44, B13-DR7, A30-B13-DR7 and A2-B46-DR9 haplotypes and linkage disequilibrium value were significantly decreased (P<0.05) in the patient group than that in the control group. On the other hand, the frequencies of A2-B52, A31-B61, A24- B8, B60-DR9, B27-DR4, B52-DR14, B44-DR17, B27-DR12 and A11-B27-DR12 haplotypes and linkage disequilibrium value were significantly increased (P<0.05) in the patient group than that in the control group. CONCLUSION: There are some common and positive linkage disequilibrium haplotypes in both the ALL patients and the healthy donors in Northern Chinese Han. Interestingly, some haplotypes and their linkage disequilibrium patterns had significantly different distributions between the two groups. The study provided basic data for the relationship of ALL and HLA haplotype and for finding the HLA-A, B, DR matching donors.

Study on the High Yield Strain of Gentamicin Producer by Protoplast Fused and Fermentor Test / 中国生物工程杂志

The protoplasts of Micromonospora purpurea,the high yield strains of gentammicin producer were mutagenized by diethyl sulfate(DES)and ultraviolet radiation(UV)respectively,then fused,screened by gentamicin resistance and regenerated.The average fermentation unit 2200?U/ml could be achieved by shake flask for 10 batches.The average fermentation unit 1900?U/ml could be obtained by 5L fermentor for 7 batches.The quality of the end product conformed to CP2000,BP2000 and USP26 pharmacopoeia.