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Identification of the novel HLA-DPA1*01:88 allele by next-generation sequencing.

ABSTRACT: The novel HLA-DPA1*01:88 allele differs from HLA-DPA1*01:03:01:05 by one nucleotide substitution in Exon 3.

SUBMITTER: Tiziana G

PROVIDER: S-EPMC9540515 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Identification of the novel HLA-DPA1*01:88 allele by next-generation sequencing.

Tiziana Galluccio G Maria Pinto Rita PR Giuseppe Testa T Andrea Di Luzio DL Marco Andreani A

HLA 20220629 4

The novel HLA-DPA1*01:88 allele differs from HLA-DPA1*01:03:01:05 by one nucleotide substitution in Exon 3. ...[more]

PMID: 35708918

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The novel HLA class I allele, HLA-B*14:110, identified by next-generation sequencing.

Project description:The novel HLA-allele B*14:110, differs from B*14:02:01:01, by one nucleotide substitution, c.T247A in exon 2.

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Characterization of the novel HLA-C*14:124 allele by next generation sequencing.

Project description:HLA-C*14:124 differs from C*14:02:01:01 by one nucleotide substitution at position 757 in exon 4.

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Deconstruction of HLA-DRB1*04:01:01 and HLA-DRB1*15:01:01 class II haplotypes using next-generation sequencing in European-Americans with multiple sclerosis.

Project description:BackgroundThe association between HLA-DRB1*15:01 with multiple sclerosis (MS) susceptibility is well established, but the contribution of the tightly associated HLA-DRB5*01:01 allele has not yet been completely ascertained. Similarly, the effects of HLA-DRB1*04:01 alleles and haplotypes, defined at the full-gene resolution level with MS risk remains to be elucidated.ObjectivesTo characterize the molecular architecture of class II HLA-DR15 and HLA-DR4 haplotypes associated with MS.MethodsNext-generation sequencing was used to determine HLA-DQB1, HLA-DQA1, and HLA-DRB1/4/5 alleles in 1403 unrelated European-American patients and 1425 healthy unrelated controls. Effect sizes of HLA alleles and haplotypes on MS risk were measured by odds ratio (OR) with 95% confidence intervals.ResultsHLA-DRB1*15:01:01:01SG (OR = 3.20, p < 2.2E-16), HLA-DRB5*01:01:01 (OR = 2.96, p < 2.2E-16), and HLA-DRB5*01:01:01v1_STR1 (OR = 8.18, p = 4.3E-05) alleles all occurred at significantly higher frequencies in MS patients compared to controls. The most significant predis-posing haplotypes were HLA-DQB1*06:02:01~ HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01 and HLA-DQB1*06:02:01~HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01v1_STR1 (OR = 3.19, p < 2.2E-16; OR = 9.30, p = 9.7E-05, respectively). Analyses of the HLA-DRB1*04 cohort in the absence of HLA-DRB1*15:01 haplotypes revealed that the HLA-DQB1*03:01:01:01~HLA-DQA1*03:03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was protective (OR = 0.64, p = 0.028), whereas the HLA-DQB1*03:02:01~HLA-DQA1*03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was associated with MS susceptibility (OR = 1.66, p = 4.9E-03).ConclusionHLA-DR15 haplotypes, including genomic variants of HLA-DRB5, and HLA-DR4 haplotypes affect MS risk.

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Identification of a novel DPA1 allele, DPA1*010602, in an East African population.

Project description:We report here a novel DPA1 allele, DPA1*010602, which was identified from an East African population during sequence-based human leukocyte antigen DPA1 typing. Through cloning and sequencing of multiple clones we confirmed that the new allele is identical to DPA1*010301 at exon 2 with the exception of two nucleotide substitutions (ATG to CAG) at codon 31. The substitutions changed the amino acid at codon 31 from methionine to glutamine. The World Health Organization nomenclature committee named the new allele DPA1*010602.

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Project description:HLA-DPB1*1348:01 differs from HLA-DPB1*14:01:01:01 by one nucleotide substitution in codon 147 in exon 3.

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Characterization of the novel HLA-DQA1*02:01:14 allele by sequencing-based typing.

Project description:HLA-DQA1*02:01:14 differs from HLA-DQA1*02:01:01:02 by one nucleotide substitution in codon 105 in exon 3.

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Characterization of the novel HLA-C*17:01:18 allele by sequencing-based typing.

Project description:HLA-C*17:01:18 differs from HLA-C*17:01:01:05 by one nucleotide substitution in codon 18 in exon 2.

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Next Generation Sequencing Identifies the HLA-DQA1*03:03 Allele in the Type 1 Diabetes Risk-Associated HLA-DQ8 Serotype.

Project description:The highest genetic type 1 diabetes risk is conferred by HLA class II haplotypes defined by alleles at the HLA-DR and -DQ loci. The combination of HLA-DQA1*03:01 and DQB1*03:02 alleles (summarized as 'HLA-DQ8') is reported to be among the two most prevalent HLA class II haplotypes in Caucasian type 1 diabetes patients. This classification is based on conventional genotyping of exon 2 of the DQ gene locus and excludes exon 3. In this study, HLA genotyping on the type 1 diabetes susceptibility loci HLA-DRB1, DQA1 and DQB1 was performed using a high-resolution next generation sequencing method. In addition to the routinely examined exon 2, exon 3 was also sequenced. Samples from 229 children with type 1 diabetes were included and compared to a cohort of 9,786 controls. In addition to previously described HLA-DQ haplotypes in type 1 diabetes patients, we found that as well as HLA-DQA1*03:01,HLA-DQA1*03:03 also contributed to HLA-DQ8. HLA-DQA1*03:03 differs from HLA-DQA1*03:01 by one nucleotide substitution in exon 3 at position 160, leading to a single amino acid replacement. DRB1*04:05 was exclusively associated with DQA1*03:03 whereas the DRB1*04:01 haplotype comprised either DQA1*03:01 or DQA1*03:03. Significantly increased type 1 diabetes risk was confirmed for all these haplotypes with only minor differences between DQA1*03:01 and DQA1*03:03 alleles. This study identified the HLA-DQA1*03:03 allele as an addition to the already known type 1 diabetes risk haplotypes, and can contribute to more precise HLA genotyping approaches.

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