Characteristics of HLA Class I and Class II Polymorphisms in Rwandan Women

Abstract

Objective: To define HLA class I and class II polymorphisms in Rwandans. Methods: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. Results: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were ≥0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. Discussion: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.

HLA-A and -B allele expression and ability to develop anti-Gag cross-clade responses in subtype C HIV-1–infected Ethiopians

“…In this study, this strong difference was related to the high frequency of HLA-B42 and -B81 alleles in the African versus the white population. According to our data, the Ethiopian population in this cohort had a frequency of HLA-A3 ϩ individuals that was higher than that observed in South Africans and closer to that of whites [44,45]. Although the p17 (aa 1-60) region has a high number of HLA-A3-restricted epitopes, we did not find a significant cluster of HLA-A3 ϩ individuals responding to p17.…”

Human Leukocyte Antigen Class I Genotypes in Relation to Heterosexual HIV Type 1 Transmission within Discordant Couples

“…Common HLA-B (B) and HLA-C (C) haplotypes were initially assigned manually according to known patterns of strong linkage disequilibrium (LD) for well-documented and fully resolved alleles observed in African-Americans (28) and for medium-resolution typing results from a native African (Rwandan) population (29). Observation of common B–C haplotypes in homozygous state provided additional assurance of accuracy in manual haplotype assignment.…”

Positive and Negative Associations of Human Leukocyte Antigen Variants with the Onset and Prognosis of Adult Glioblastoma Multiforme

“…Phi29 DNA polymerase and random hexamers were used for whole genome amplification, following protocols recommended by the manufacturer (Amersham Biosciences, Piscataway, NJ), as described in detail elsewhere (44). A combination of PCRbased techniques, including solid-phase sequencing, PCR with sequence-specific primers and automated, reference strandmediated conformation analyses, resolved individual alleles from the classical HLA genes HLA-A, -B, -C, and -DRB1 at chromosome 6p21.3 (44,45). Alleles of the TNFb microsatellite [short tandem repeat (STR) sequence] and of another STR in exon 5 of the MHC class I-like chain A (MICA) gene were resolved through PCR amplification and automated, denaturing gel electrophoresis (44).…”