Distribution of HLA-A, B, C Allele and Haplotype Frequencies in Koreans / 대한진단검사의학회지

BACKGROUND: The HLA system is known to be the most polymorphic gene cluster in the human genome. HLA allele and haplotype distribution varies widely among different ethnic groups. In this study, we examined the frequency of HLA class I alleles and haplotypes in 309 healthy Koreans. METHODS: We typed HLA-A, -B, and -C genes at the allelic level in 109 unrelated Korean individuals using a sequence-based typing. With the additional data of 200 healthy Koreans from dbMHC (http: //www.ncbi.nlm.nih.gov/mhc/), allele and haplotype frequencies were estimated by the maximum likelihood method. Serological typing results of 49 individuals were compared with the results highly resolved. RESULTS: A total of 22 HLA-A, 41 HLA-B, and 21 HLA-C alleles were found in this study. Alleles showing frequencies of more than 10% in each HLA locus were A*2402 (22.5%), A*0201 (15.7%), A*3303 (14.4%), A*1101 (11.0%), B*5101 (12.1%), Cw*0102 (18.8%), and Cw*1402 (10.2%). The most common A-B-C haplotypes at a frequency of more than 3% were A*3303-B*5801-Cw*0302 (5.2%), A*2402-B*5101-Cw*1402 (4.5%), A*1101-B*1501-Cw*0401 (4.3%), A*3303-B*4403-Cw*1403 (4.0%), A*3001-B*1302-Cw*0602 (3.7%), and A*0207-B*4601-Cw*0102 (3.2%). Misassignment of HLA-C antigen by serotyping was detected in 11 (22.4%) of 49 individuals. CONCLUSIONS: Our results will be useful as a basic data for studies on anthropology, disease association, and bone marrow transplantation. Misidentification of HLA-C by serotyping is so high that it would be desirable to perform a DNA typing especially in unrelated bone marrow transplantation.

HLA-A, -B, -DR Allele Frequencies and Haplotypic Associations in Koreans Defined by Generic-Level DNA Typing / 대한진단검사의학회지

BACKGROUND: HLA allele and haplotype distribution varies widely among different ethnic groups. For organ transplantation, anthropology and disease association studies, reliable data on the HLA distribution in each ethnic group is needed. In recent years, more accurate DNA typing methods are increasingly used in place of the serologic typing method. METHODS: We examined HLA-A, -B, and -DR alleles at the generic (serologic) level in 1, 600 Koreans registered for the Korea Marrow Donor Program (KMDP) using the PCR-sequence specific oligonucleotide (SSO) method (Dynal RELI(TM) kit). Allele and haplotype frequencies were estimated by the maximum likelihood method using the computer program developed for the 11th International Histocompatibility Workshop. RESULTS: HLA alleles found in Koreans were 13 in A, 31 in B, and 13 in DR locus. Most frequent alleles with frequencies > or =10% were: A2, A24, A33, A11; B62, B44, B51; DR4, DR15, DR13, and DR8 in each locus in decreasing order of frequency. Subtype frequencies of B61 and B75 serologic specificities were identified: B*4002 (51.1%), *4003 (7.6%) and *4006 (41.3%) for B61, and B*1502 (9.5%) and *1511 (90.5%) for B75. Two-locus haplotypes with frequencies> or =0.1% were presented (99 A-B, 115 B-DR), among which those with frequencies> or =1.0% showing significant positive linkage disequilibrium (P or =0.1% were identified in Koreans, among which 38 haplotypes showed frequencies> or =0.5%. We compared the results of this study with those of our previous study of serologically typed HLA-A, -B and DNA typed HLA-DR in 2, 000 Koreans. Results from the two studies were similar, but blank frequencies were decreased to 0% for HLA-A, -B, and -DR locus compared with the frequencies of 0.3-0.8% in the previous study (A, 0.3%; B, 0.8%; DR, 0.3%) and all of the serologic splits could be assigned in this study. CONCLUSIONS: In this study, we provided the allele and haplotype frequencies of HLA-A, -B, and -DR in Koreans defined by a DNA typing method, which can be used as basic data on Koreans for organ transplantation and disease association studies.

Molecular genetics analysis of a Chinese family carrying triple HLA-A antigen / 中国输血杂志

Objective A rare HLA phenotype carrying three HLA-A antigens, A2, A11.2 and A24, was identified in a potential bone marrow donor SZHD1. Methods To determine molecular basis of this phenotype the HLA-A gene fragments from this donor and his family members were cloned and sequenced. Results Sequencing analysis indicated that the donor carries an unusual HLA haplotype, A*1102, A*24020101; B*38; DRB1*15. Conclusions Other four family members were found to carry this haplotype, which as a Mendelian gene was segregated and stably transmitted through three generations. This is a first example of a family carrying triple HLA-A antigens to the best of our knowledge.

Prenatal diagnosis of a heterozygote of salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency by genetic linkage analysis

For the purpose of prenatal diagnosis of CAH, genetic linkage analysis by HLA genotyping with lymphocytes and cultured amniotic cells were performed in a family at risk in which two consecutive children had been affected with SW CAH. In addition, the response of serum 17-OHP to intravenous ACTH was determined in obligate carrier parents, and 17-OHP concentration of amniotic fluid was also measured at 16 weeks of gestation. As might be expected, the baseline levels of 17-OHP in obligate parents were significantly higher than that of normal control. Although the post stimulation response of 17-OHP to ACTH in the mother (I-2) was significantly higher than that of normal control, the post stimulation levels of 17-OHP were in normal range in the father (I-1). The 17-OHP level (5.7 ng/ml) in the amniotic fluid showed intermediate value compared to Pang's report (normal less than 30 ng/ml, CAH greater than 12.0 ng/ml) suggesting heterozygote of the fetus. Genetic linkage analysis by HLA genotyping with cultured amniotic cells revealed heterozygote in their fetus (II-3) who has received one chromosome No,6 containing HLA haplotype A24, B40, Cw3 (normal allele for 21-OH) from the father and the other chromosome No,6 containing HLA haplotype A2, Bw62, Cw4 (mutant allele for 21-OH D) from the mother. In conclusion, attempts to detect heterozygote for 21-OH deficiency by ACTH stimulation test were partially successful and prenatal diagnosis of CAH by the hormone studies in ammiotic fluid requires reliable values in normal, heterozygotes and patients group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)