Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates
Abstract Aside from its anthropological relevance, the characterization of the allele frequencies of genes in the human Major Histocompatibility Complex (MHC) and the combination of these alleles that make up MHC conserved extended haplotypes (CEHs) is necessary for histocompatibility matching in tr...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-11256-y |
| _version_ | 1817985391797469184 |
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| author | Halima Alnaqbi Guan K. Tay Sarah El Hajj Chehadeh Habiba Alsafar |
| author_facet | Halima Alnaqbi Guan K. Tay Sarah El Hajj Chehadeh Habiba Alsafar |
| author_sort | Halima Alnaqbi |
| collection | DOAJ |
| description | Abstract Aside from its anthropological relevance, the characterization of the allele frequencies of genes in the human Major Histocompatibility Complex (MHC) and the combination of these alleles that make up MHC conserved extended haplotypes (CEHs) is necessary for histocompatibility matching in transplantation as well as mapping disease association loci. The structure and content of the MHC region in Middle Eastern populations remain poorly characterized, posing challenges when establishing disease association studies in ethnic groups that inhabit the region and reducing the capacity to translate genetic research into clinical practice. This study was conceived to address a gap of knowledge, aiming to characterize CEHs in the United Arab Emirates (UAE) population through segregation analysis of high-resolution, pedigree-phased, MHC haplotypes derived from 41 families. Twenty per cent (20.5%) of the total haplotype pool derived from this study cohort were identified as putative CEHs in the UAE population. These consisted of CEHs that have been previously detected in other ethnic groups, including the South Asian CEH 8.2 [HLA- C*07:02-B*08:01-DRB1*03:01-DQA1*05:01-DQB1*02:01 (H.F. 0.094)] and the common East Asian CEH 58.1 [HLA- C*03:02-B*58:01-DRB1*03:01- DQA1*05:01-DQB1*02:01 (H.F. 0.024)]. Additionally, three novel CEHs were identified in the current cohort, including HLA- C*15:02-B*40:06-DRB1*16:02-DQB1*05:02 (H.F. 0.035), HLA- C*16:02-B*51:01-DRB1*16:01-DQA1*01:02-DQB1*05:02 (H.F. 0.029), and HLA- C*03:02-B*58:01-DRB1*16:01-DQA1*01:02-DQB1*05:02 (H.F. 0.024). Overall, the results indicate a substantial gene flow with neighbouring ethnic groups in the contemporary UAE population including South Asian, East Asian, African, and European populations. Importantly, alleles and haplotypes that have been previously associated with autoimmune diseases (e.g., Type 1 Diabetes) were also present. In this regard, this study emphasizes that an appreciation for ethnic differences can provide insights into subpopulation-specific disease-related polymorphisms, which has remained a difficult endeavour. |
| first_indexed | 2024-04-13T23:57:33Z |
| format | Article |
| id | doaj.art-74ddcdb19f6e4a708c7966a327673363 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T23:57:33Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-74ddcdb19f6e4a708c7966a3276733632022-12-22T02:23:50ZengNature PortfolioScientific Reports2045-23222022-05-0112111410.1038/s41598-022-11256-yCharacterizing the diversity of MHC conserved extended haplotypes using families from the United Arab EmiratesHalima Alnaqbi0Guan K. Tay1Sarah El Hajj Chehadeh2Habiba Alsafar3Center for Biotechnology, Khalifa University of Science and TechnologyCenter for Biotechnology, Khalifa University of Science and TechnologyCenter for Biotechnology, Khalifa University of Science and TechnologyCenter for Biotechnology, Khalifa University of Science and TechnologyAbstract Aside from its anthropological relevance, the characterization of the allele frequencies of genes in the human Major Histocompatibility Complex (MHC) and the combination of these alleles that make up MHC conserved extended haplotypes (CEHs) is necessary for histocompatibility matching in transplantation as well as mapping disease association loci. The structure and content of the MHC region in Middle Eastern populations remain poorly characterized, posing challenges when establishing disease association studies in ethnic groups that inhabit the region and reducing the capacity to translate genetic research into clinical practice. This study was conceived to address a gap of knowledge, aiming to characterize CEHs in the United Arab Emirates (UAE) population through segregation analysis of high-resolution, pedigree-phased, MHC haplotypes derived from 41 families. Twenty per cent (20.5%) of the total haplotype pool derived from this study cohort were identified as putative CEHs in the UAE population. These consisted of CEHs that have been previously detected in other ethnic groups, including the South Asian CEH 8.2 [HLA- C*07:02-B*08:01-DRB1*03:01-DQA1*05:01-DQB1*02:01 (H.F. 0.094)] and the common East Asian CEH 58.1 [HLA- C*03:02-B*58:01-DRB1*03:01- DQA1*05:01-DQB1*02:01 (H.F. 0.024)]. Additionally, three novel CEHs were identified in the current cohort, including HLA- C*15:02-B*40:06-DRB1*16:02-DQB1*05:02 (H.F. 0.035), HLA- C*16:02-B*51:01-DRB1*16:01-DQA1*01:02-DQB1*05:02 (H.F. 0.029), and HLA- C*03:02-B*58:01-DRB1*16:01-DQA1*01:02-DQB1*05:02 (H.F. 0.024). Overall, the results indicate a substantial gene flow with neighbouring ethnic groups in the contemporary UAE population including South Asian, East Asian, African, and European populations. Importantly, alleles and haplotypes that have been previously associated with autoimmune diseases (e.g., Type 1 Diabetes) were also present. In this regard, this study emphasizes that an appreciation for ethnic differences can provide insights into subpopulation-specific disease-related polymorphisms, which has remained a difficult endeavour.https://doi.org/10.1038/s41598-022-11256-y |
| spellingShingle | Halima Alnaqbi Guan K. Tay Sarah El Hajj Chehadeh Habiba Alsafar Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates Scientific Reports |
| title | Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates |
| title_full | Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates |
| title_fullStr | Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates |
| title_full_unstemmed | Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates |
| title_short | Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates |
| title_sort | characterizing the diversity of mhc conserved extended haplotypes using families from the united arab emirates |
| url | https://doi.org/10.1038/s41598-022-11256-y |
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