Identification of Four Novel HLA-A Alleles from an East African Population by High-Resolution Sequence-Based Typing (original) (raw)
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A novel human leucocyte antigen (HLA)-A allele, HLA-A*01:195, was identified by sequence-based typing (SBT) in a UAE national subject. The novel allele is identical to its closest known allele, HLA-A*01:01:01:01, in exon 2, 3 and 4, except for a single nucleotide mutation of A to G at position 442 in exon 3 (codon 124 in the a2 domain of the a chain of the mature protein). This A to G mutation results in an amino acid change of isoleucine #124 to valine.
Tissue Antigens, 2008
We describe two novel human leukocyte antigen (HLA) alleles, HLA-A*02010103 and HLA-B*4455, that were discovered in two unrelated Caucasian individuals. In addition, we report the full-length genomic sequence of HLA-A*290201. Compared with HLA-A*02010101, HLA-A*02010103 has three nucleotide (nt) changes within intron 1, which is altered to a sequence typical of the HLA-A*23/A*24 allele group. In HLA-B*4455, an nt exchange occurred in codon 9 of HLA-B*44020101, resulting in a change of the amino acid coding from tyrosine to histidine. We sequenced HLA-A*290201 from nt −108 to nt 2922, encompassing all exons and introns as well as parts of the 5′ and 3′ untranslated regions. Previously, the full-length genomic sequence was known only for HLA-A*29010101, which is found at a lower frequency in Caucasians than HLA-A*290201.
HLA-G exhibits low level of polymorphism in indigenous East Africans
Human Immunology, 2002
Human leukocyte antigen G (HLA-G) is a nonclassical HLA class I antigen that is predominantly expressed on invasive cytotrophoblastic cells, and is postulated to be a mediator of maternal-fetal tolerance. Almost all studies in Caucasian and Asian populations have consistently reported that HLA-G exhibits low levels of allelic polymorphism unlike the classical class I genes. However, the concept that HLA-G is nonpolymorphic has recently been challenged in a single study of African-American subjects. We have examined the DNA sequences of the first seven HLA-G exons by single-strand conformational polymorphism (SSCP) and DNA direct sequencing procedures in 45 healthy individuals from an indigenous African population. Overall, we detected 14 sequence variations: 3 in the signal peptide (exon 1); 2 in the ␣-1 domain (exon 2); 5 in the ␣-2 domain (exon 3); 2 in ␣-3 domain (exon 4); 2 in transmembrane domain (exon 5); and none in the cytoplasmic tail (exons 6 and 7). Of these variants, only three result in amino acid substitutions at the protein level. Of particular interest, we identified a novel nucleotide substitution (C727T), 56 bp before the HLA-G gene transcription start site, located in the putative binding site for polyomavirus enhancer-binding protein 2 (PEBP2) transcriptor factor. These data confirm previous reports describing HLA-G exhibiting limited allelic polymorphism. Further studies are needed to determine the impact of the C727T polymorphism on the level or developmental regulation of HLA-G expression.
Identification of Two Novel HLA-C Alleles, Cw*070105 and Cw*1408, from East African Women
Human Immunology, 2006
HLA-C was shown to be a highly polymorphic gene that can be accurately typed by sequencing methodologies. We report two novel HLA-C alleles identified during sequence-based typing of East African populations; the novel alleles were confirmed by sequencing two separate polymerase chain reaction products and by molecular cloning and sequencing multiple clones. The first new allele is identical to Cw*0701 except for a single-nucleotide synonymous substitution at codon 182 (GCA¡GCG). The new allele has been named by the WHO nomenclature committee as Cw*070105. The second new allele is identical to Cw*1403 except for a nonsynonomous change at codon 21 (CAC¡CGC), changed from histidine to arginine. The new allele has been named by the WHO nomenclature committee as
Human Immunology, 2008
We report two novel human leukocyte antigen G (HLA-G) alleles identified in an East African population during sequence-based typing of HLA-G. The novel alleles were confirmed by sequencing multiple polymerase chain reaction products and molecular cloning and subsequent sequencing of multiple clones. The sequence of HLA-G*0110 (EU290672) is identical to G*01010101/01010102/01010103/01010104/01010105 at exons 2, 3, and 4 except for a single nucleotide difference at codon 31 (ACG --> ATG), resulting in a coding change from threonine to methionine. The sequence of HLA-G*0111 (EU290673) is identical to G*010404 at exons 2, 3, and 4 except for a single nucleotide difference at codon 31 (ACG --> ATG), resulting in a coding change from threonine to methionine. These new alleles are detected in several other individuals in our study population and the functional relevance of these new alleles must be studied.
Human Immunology, 2011
HLA-G*01:17 was discovered in a woman of Kenyan descent who was enrolled in a mother-to-child HIV-1 transmission cohort. The new allele was identical to HLA-G*01:06 at exons 2, 3, and 4 with the exception of a base pair substitution at codon 169 (CAC¡CGC) resulting in a coding change from histidine to arginine and codon 171 (TAC¡CAC), resulting in turn in a coding change from tyrosine to histidine. The World Health Organization (WHO) Nomenclature Committee has named this allele HLA-G*01:17.
HLA-A*3306, a novel variant in the Indian population
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We describe a new HLA-A allele, A*3306, which was identified by sequencing based typing (SBT) in an individual of Indian origin. A*3306 is similar to A*3303, with a difference at position 228 (A to G). This difference leads to an amino-acid change at codon 52 from Ile (ATA) to Met (ATG). Until now this position has been considered conserved.
Diversity and Frequencies of HLA Class I and Class II Genes of an East African Population
Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.