HLA‐G whole gene amplification reveals linkage disequilibrium between the HLA‐G 3′UTR and coding sequence
| Autor: | Jos J.M. Drabbels, Erik H. Rozemuller, Robert Welleweerd, Geert W. Haasnoot, Guro M. Johnsen, Inge van Rooy, Anne Cathrine Staff, Michael Eikmans, Frans H.J. Claas, Nienke Westerink |
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| Rok vydání: | 2020 |
| Předmět: |
Untranslated region
haplotype Linkage disequilibrium HLA-G Immunology HLA‐G 3′‐UTR Human leukocyte antigen Biology Polymorphism Single Nucleotide Linkage Disequilibrium 3 '-UTR Gene Frequency Pregnancy Genetics Humans Immunology and Allergy Coding region Typing Child 3' Untranslated Regions Gene Alleles next generation sequencing HLA-G Antigens Haplotype allele Gene Amplification Original Articles Infectious Disease Transmission Vertical Transplantation Haplotypes Original Article Female |
| Zdroj: | Hla HLA: Immune Response Genetics, 96(2), 179-185. WILEY |
| ISSN: | 2059-2310 2059-2302 |
| DOI: | 10.1111/tan.13909 |
| Popis: | Polymorphic sites in the HLA-G gene may influence expression and function of the protein. Knowledge of the association between high-resolution HLA-G alleles and 3-prime untranslated (3 ' UTR) haplotypes is useful for studies on the role of HLA-G in transplantation, pregnancy, and cancer. We developed a next generation sequencing (NGS)-based typing assay enabling full phasing over the whole HLA-G gene sequence with inclusion of the 3 ' UTR region. DNA from 171 mother-child pairs (342 samples) was studied for: (a) HLA-G allele information by the NGSgo-AmpX HLA-G assay, (b) 3 ' UTR haplotype information by an in-house developed sequence-based typing method of a 699/713 base pair region in the 3 ' UTR, and (c) the full phase HLA-G gene sequence, by combining primers from both assays. The mother to child inheritance allowed internal verification of newly identified alleles and of association between coding and UTR regions. The NGSgo workflow compatible with Illumina platforms was employed. Data was interpreted using NGSengine software. In 99.4% of all alleles analyzed, the extended typing was consistent with the separate allele and 3 ' UTR typing methods. After repeated analysis of four samples that showed discrepancy, consistency reached 100%. A high-linkage disequilibrium between IPD-IMGT/HLA Database-defined HLA-G alleles and the extended 3 ' UTR region was identified (D ' = 0.994, P < .0001). Strong associations were found particularly between HLA-G*01:04 and UTR-3, between HLA-G*01:01:03 and UTR-7, and between HLA-G*01:03:01 and UTR-5 (for all: r = 1). Six novel HLA-G alleles and three novel 3 ' UTR haplotype variants were identified, of which three and one, respectively, were verified in the offspring. |
| Databáze: | OpenAIRE |
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