Departament of Immunology, School of Medicine, University Complutense of Madrid, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Sci Rep. 2023 Oct 4;13(1):16711. doi: 10.1038/s41598-023-42016-1.
HLA and disease studies by using single allele statistics have been fruitless during the last 40 years for explaining association pathogenesis of the associated diseases.Other approaches are necessary to untangle this puzzle. We aim to revisit complement alleleism in humans and primates for both studying MHC and disease association to complotypes and extended MHC haplotypes in order to also explain the positive directional selection of maintaining immune response genes (complement, MHC adaptive and MHC non-specific genes) that keeps these three type of genes together in a short chromosome stretch (MHC) for million years. These genes may be linked to conjointly avoid microbes attack and autoimmunity. In the present paper, it is obtained a new Bf chimpanzee allele, provisionaly named Patr-BfA:01,that differs from other Bf alleles by having CTG at eleventh codon of exon 2 in order to start the newly suggested methodology and explain functional and evolutionary MHC obscure aspects. Exons 1 to 6 of Ba fragment of Bf gene were obtained from chimpanzee. This new chimpanzee Factor B allele (Patr-BfA:01) is to be identical to a infrequent human Bf allele (SNP rs641153); it stresses the strong evolutive pressure upon certain alleles that are trans specific. It also may apply to MHC extended haplotipes which may conjointly act to start an adequate immune response. It is the first time that a complement MHC class III allele is described to undergo trans species evolution,in contrast to class I and class II alleles which had already been reported . Allelism of complement factors are again proposed for studying MHC complement genes, complotypes, and extended MHC haplotypes which may be more informative that single MHC marker studies.
在过去的 40 年中,使用单等位基因统计数据研究 HLA 与疾病的关系,对于解释相关疾病的关联发病机制并没有取得成果。需要其他方法来解开这个难题。我们旨在重新研究人类和灵长类动物的补体等位基因,以研究 MHC 与疾病的关联,以及 complotypes 和扩展的 MHC 单倍型,以便解释维持免疫反应基因(补体、MHC 适应性和 MHC 非特异性基因)正向选择的原因,这些基因在短染色体(MHC)上保持在一起已有上百万年的时间。这些基因可能与共同避免微生物攻击和自身免疫有关。在本文中,获得了一个新的 Bf 黑猩猩等位基因,暂时命名为 Patr-BfA:01,与其他 Bf 等位基因不同,它在第 2 外显子的第 11 位密码子处有 CTG,以便开始新的建议方法,并解释 MHC 功能和进化方面的模糊方面。从黑猩猩中获得了 Bf 基因 Ba 片段的外显子 1 至 6。这种新的黑猩猩因子 B 等位基因(Patr-BfA:01)与一种罕见的人类 Bf 等位基因(SNP rs641153)相同;这强调了某些等位基因受到强烈进化压力的影响,这些等位基因是跨物种的。它也可能适用于 MHC 扩展单倍型,这些单倍型可能共同作用以启动适当的免疫反应。这是第一次描述补体 MHC 类 III 等位基因发生跨物种进化,而类 I 和类 II 等位基因已经有报道。再次提出补体因子的等位基因用于研究 MHC 补体基因、complotypes 和扩展的 MHC 单倍型,这些研究可能比单个 MHC 标记研究更具信息量。