Phylogenetic analyses of the HLA-DRB1 gene based on the DR haplotypes
| Project/Area Number |
14340237
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
遺伝
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| Research Institution | National Center of Neurology and Psychiatry (NCNP) |
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Principal Investigator |
HOHJOH Hirohiko National Center of Neurology and Psychiatry (NCNP), National Institute of Neuroscience, Section Chief, 疾病研究第三部, 室長 (60238722)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUNAGA Katsushi University of Tokyo, Grad. Schl. of Medicine, Professor, 大学院・医学系研究科, 教授 (40163977)
ISHIDA Takafumi University of Tokyo, Grad. Schl. of Science, Associate Professor, 大学院・理学系研究科, 助教授 (20184533)
KUNUGI Hiroshi National Center of Neurology and Psychiatry (NCNP), National Institute of Neuroscience, Director, 疾病研究第三部, 部長 (40234471)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | HLA / DRB1 gene / Haplotype / Phylogenic tree / DR53 group |
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| Research Abstract |
The human leukocyte antigen (HLA)-DRB1 is a highly polymorphic gene with a large number of alleles in the human genome, and the DR subregion including DRB1 also possesses polymorphism in terms of its genome organization with active DRB genes and their pseudogenes. Classification of DRB1 alleles based on the DR groups seems to be an important parameter for studying the phylogeny of the DRB1 alleles. Conventional phylogenetic trees for the HLA-DRB1 alleles constructed by the neighbor-joining and UPGMA methods using nucleotide sequences of the DRB1 alleles suggest that DRB1^*0701 may have diverged from other DRB1 alleles before the separation of the human and chimpanzee species because of a large number of nucleotide changes in DRB1^*0701 compared with any of the other DRB1 alleles. In this study we show the new evidence that the haplotypes centering on DRB1^*0701 and DRB1^*04 alleles are the most homologous. This suggests that these haplotypes have derived from the common-ancestral haplo
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type, and that they have likely retained the complete linkage disequilibrium even after the divergence of the DRB1^*0701 and DRB1^*04 allelic lineages. Together with the corresponding haplotype carrying chimpanzee DRB1^*0701 which has a high sequence homology to HLA-DRB1^*0701,these haplotypes reveal that : i)the DRB1^*04 allelic lineage may have been generated from the DRB1^*0701 lineage after the separation of the human and chimpanzee species, ii)the DRB1^*04 allelic lineage has possibly higher substitution rate of DRB1 compared with pseudogene and neutral region, and iii)there could be a significant difference in the substitution rate of DRB1 between the DRB1^*0701 and DRB1^*04 allelic lineages. Based on the difference between the present and previous results, we would like to propose that phylogenetic studies using not only nucleotide sequences of the DRB1 alleles but also haplotypes centering on the alleles should be conducted for understanding detailed phylogenetic relationships of the DRB1 alleles. Less
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(3 results)
Research Products
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