Multiple divergent haplotypes express completely distinct sets of class I MHC genes in zebrafish.
Multiple divergent haplotypes express completely distinct sets of class I MHC genes in zebrafish.
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DOI：
10.1007/s00251-013-0749-y
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发表时间：
2014-03
期刊：
影响因子：
3.2
通讯作者：
de Jong, Jill L. O.
中科院分区：
文献类型：
--
作者：
McConnell, Sean C.;Restaino, Anthony C.;de Jong, Jill L. O.
斑马鱼是干细胞生物学、癌症和免疫学研究的重要动物模型。组织相容性代表了这些学科的关键交叉点，但斑马鱼的组织相容性仍然知之甚少。我们研究了一组不同的斑马鱼I类主要组织相容性复合体（MHC）基因，分离与特定的单倍型在19号染色体，供受体匹配已被证明可以提高造血移植后的植入。使用侧翼基因多态性，我们确定了6个不同的19号染色体单倍型。我们描述了几个新的I类U谱系基因，并表征其序列特性，表达和单倍型分布。总共分析了10个全长斑马鱼I类基因，mhc1uba到mhc1uka。表达数据和序列特征表明，大多数是候选的经典基因。推定的肽锚残基中的几个取代，通常与来自其他硬骨鱼物种的推导的MHC分子共享，表明抗原结合的灵活性。所有10个斑马鱼I类基因在6个单倍型中唯一分配，每个单倍型具有1至3个基因的显性或共显性表达。有趣的是，虽然不同的MHC单倍型显示不同的基因拷贝数和内容，不同的基因似乎有古老的起源，具有极高的序列多样性水平。此外，单倍型变异性超出了MHC基因，包括不同形式的psmb8。因此，在这个基因座上的许多不同的单倍型代表了基因组区域构型多态性的显著形式。在这些不同的I类单倍型在斑马鱼的功能性MHC基因的定义将提供一个重要的基础，在未来的免疫学和移植的研究。
The zebrafish is an important animal model for stem cell biology, cancer, and immunology research. Histocompatibility represents a key intersection of these disciplines, however histocompatibility in zebrafish remains poorly understood. We examined a set of diverse zebrafish Class I major histocompatibility complex (MHC) genes that segregate with specific haplotypes at chromosome 19, and for which donor-recipient matching has been shown to improve engraftment after hematopoietic transplantation. Using flanking gene polymorphisms we identified six distinct chromosome 19 haplotypes. We describe several novel Class I U lineage genes and characterize their sequence properties, expression, and haplotype distribution. Altogether ten full-length zebrafish Class I genes were analyzed, mhc1uba through mhc1uka. Expression data and sequence properties indicate that most are candidate classical genes. Several substitutions in putative peptide anchor residues, often shared with deduced MHC molecules from additional teleost species, suggest flexibility in antigen binding. All ten zebrafish Class I genes were uniquely assigned among the six haplotypes, with dominant or co-dominant expression of one to three genes per haplotype. Interestingly, while the divergent MHC haplotypes display variable gene copy number and content, the different genes appear to have ancient origin, with extremely high levels of sequence diversity. Furthermore, haplotype variability extends beyond the MHC genes to include divergent forms of psmb8. The many disparate haplotypes at this locus therefore represent a remarkable form of genomic region configuration polymorphism. Defining the functional MHC genes within these divergent Class I haplotypes in zebrafish will provide an important foundation for future studies in immunology and transplantation.
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影响因子：
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通讯作者：
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