Diversity and characterisation of polymorphic 3' untranslated region haplotypes of <i>MICA</i> and <i>MICB</i> genes

Cox, S.T.; Hernandez, Diana; Danby, Robert; Turner, Thomas R.; Madrigal, J. Alejandro

doi:10.1111/tan.13434

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…For individual samples, genotyping results with three-field resolution can be generated using long-read sequencing technologies (48). Moreover, our amplicon strategy does not include the 5 ′ and 3 ′ UTRs of MICA/B which contain additional polymorphic positions (49,50). Some of them influence (s)MICA/B expression which varies between different alleles (18,(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

High-Throughput MICA/B Genotyping of Over Two Million Samples: Workflow and Allele Frequencies

et al. 2020

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MICA and MICB are ligands of the NKG2D receptor and thereby influence NK and T cell activity. MICA/B gene polymorphisms, expression levels and the amount of soluble MICA/B in the serum have been linked to autoimmune diseases, infections, and cancer. In hematopoietic stem cell transplantation, MICA matching between donor and patient has been correlated with reduced acute and chronic graft-vs.-host disease and improved survival. Hence, we developed an extremely cost-efficient high-throughput workflow for genotyping MICA/B for newly registered potential stem cell donors. Since mid-2017, we have genotyped over two million samples using NGS amplicon sequencing for MICA/B exons 2-5. In donors of German origin, MICA * 008 is the most common MICA allele with a frequency of 42.3%. It is followed by MICA * 002 (11.7%) and MICA * 009 (8.8%). The three most common MICB alleles are MICB * 005 (43.9%), MICB * 004 (21.7%), and MICB * 002 (18.9%). In general, MICB is less diverse than MICA and only 6 alleles, instead of 15, account for a cumulative allele frequency of 99.5%. In 0.5% of the samples we observed at least one allele of MICA or MICB which has so far not been reported to the IPD/IMGT-HLA database. By providing MICA/B typed voluntary donors, clinicians become empowered to include MICA/B into their donor selection process to further improve unrelated hematopoietic stem cell transplantation.

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Section: Discussionmentioning

confidence: 99%

High-Throughput MICA/B Genotyping of Over Two Million Samples: Workflow and Allele Frequencies

et al. 2020

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“…NKG2D can be activated on NK cells, cytotoxic T cells and other T cell subsets (16-20). Major histocompatibility complex class I chain-related proteins A and B (MICA/MICB) and UL binding proteins (ULBP)1-6 are NKG2D ligands (21,22). ULBP1-6 shares similar functions with MICA and MICB, but has a different structure (21).…”

Section: Introductionmentioning

confidence: 99%

“…Major histocompatibility complex class I chain-related proteins A and B (MICA/MICB) and UL binding proteins (ULBP)1-6 are NKG2D ligands (21,22). ULBP1-6 shares similar functions with MICA and MICB, but has a different structure (21). NKG2D ligands are lowly expressed in some normal cells, but positively expressed under stimuli (20).…”

Section: Introductionmentioning

confidence: 99%

Correlations between major depressive disorder, splenic morphology and immunity

Lin,

Xu,

Zhang

et al. 2024

Preprint

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To explore the symptoms, course and severity of depressive disorder and the morphological changes of spleen and immune-related mechanism. We recruited patients with first-episode or recurrent major depressive disorder（MDD）(patient group) and healthy controls (normal group) matched in age and gender. All subjects’ plasma MICB (pg/ml), ULBP1 (ng/ml) and splenic volume (cm3) were measured at baseline. The patient group was randomly assigned to receive (S)-ketamine (study group) and non-(S)-ketamine (control group), and the above indexes were collected again on the 4th weekend after administration. At baseline, the MICB and splenic volume in patient group were significantly higher than those in normal group. There appears a positive correlation between MICB and splenic volume in the patient group. After administration of (S)-ketamine, the higher splenic volume and MICB decreased. The results indicate that the pathogenesis of MDD may involve abnormal changes in MICB expression and splenic morphology. (S)-ketamine may ameliorate the inflammation and enhance splenic function to relieve MDD symptoms.

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Widespread non‐coding polymorphism in HLA class II genes of International HLA and Immunogenetics Workshop cell lines

Turner

Hayward

Gymer

et al. 2022

HLA

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As the primary genetic determinant of immune recognition of self and non‐self, the hyperpolymorphic HLA genes play key roles in disease association and transplantation. The large, variably sized HLA class II genes have historically been less well characterized than the shorter HLA class I genes. Here, we have used Pacific Biosciences Single Molecule Real‐Time (SMRT®) DNA sequencing to perform four‐field resolution HLA typing of HLA‐DRB1/3/4/5, ‐DQA1, ‐DQB1, ‐DPA1 and ‐DPB1 from a panel of 181 B‐lymphoblastoid cell lines from the International HLA and Immunogenetics Workshops. By interrogating all exons, introns, and the untranslated regions of these important reference cells, we have improved their HLA typing resolution on the IPD‐IMGT/HLA database. We observed widespread non‐coding polymorphism, with over twice as many unique genomic sequences identified compared with coding sequences (CDS). We submitted 263 unique sequences to the IPD‐IMGT/HLA Database, often from multiple cell lines, including 114 confirmations of existing alleles, of which 30 were also extensions to full‐length genomic sequences where only CDS was available previously. A total of 149 novel alleles were identified, largely differing from their closest reference allele sequences by a single nucleotide polymorphism (SNP). However, some highly divergent alleles were deemed to be recombinants, only detectable by full‐length sequencing with long, phased reads. The fourth‐field variation we observed allowed fine mapping of linkage disequilibrium patterns and haplotypes to particular ancestries. This study has highlighted the under‐appreciated non‐coding diversity in HLA class II genes, with potential implications for population genetic and clinical studies.

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Diversity and characterisation of polymorphic 3' untranslated region haplotypes of MICA and MICB genes

Cited by 4 publications

References 38 publications

High-Throughput MICA/B Genotyping of Over Two Million Samples: Workflow and Allele Frequencies

High-Throughput MICA/B Genotyping of Over Two Million Samples: Workflow and Allele Frequencies

Correlations between major depressive disorder, splenic morphology and immunity

Widespread non‐coding polymorphism in HLA class II genes of International HLA and Immunogenetics Workshop cell lines

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