Canine major histocompatibility complex class I (MHC-I) diversity landscape.
Canine major histocompatibility complex class I (MHC-I) diversity landscape.
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犬主要组织相容性复合体 I 类 (MHC-I) 多样性景观。
DOI：
10.1101/2024.02.14.580220
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Zhao,Shaying
中科院分区：
文献类型：
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作者：
Feng,Yuan;Ho,Kun-Lin;Zhang,Mengyuan;Sundaresha,NikithaBrahmasamudra;Cavanagh,HannahLorelle;Zhao,Shaying
主要组织相容性复合体I类(MHC-I)基因是哺乳动物基因组中最多样化的基因之一，在免疫学中起着至关重要的作用。因此，了解MHC-I的多样性是至关重要的。狗是各种生物医学领域的关键翻译模型。然而，我们对犬类MHC-I多样性的了解远远落后于人类。为了解决这一缺陷，我们使用我们最新开发的软件KPRde novoAssembly and genotyper，在经过广泛的质量控制后，使用来自43个BioProjects的配对末端RNA-seq数据对来自1025只狗的1,325个样本进行了基因分型。在926只通过QC的犬中，有591只(%)至少有一个等位基因，共鉴定出97个已知等位基因和52个可能的新等位基因。进一步分析发现，DLA-I基因在不同组织中的表达水平不同，睾丸和脑组织表达水平最低，血液、黄体和脾组织表达水平最高。我们确定了17个犬种中的每一个以及整个犬类群体中的优势等位基因。此外，我们的分析还识别了品种特有的等位基因和相互共生/排斥的等位基因。我们的研究表明，犬DLA-88在整个群体中与人类的HLA-A/B/C基因一样具有多样性，但在品种内的多样性不如在种族内的HLA-A/B/C基因的多样性。最后，我们检查了人/犬MHC-I等位基因内部或之间的高变区，发现80%的高变区在两个物种之间重叠。我们进一步注意到，80%的HVR与多肽在4A接触范围内，狗与人的差异只有20%的HVR重叠。我们的研究为涉及狗的免疫学研究提供了有价值的见解。
The genes of the Major Histocompatibility Complex class I (MHC-I) are among the most diverse in the mammalian genome, playing a crucial role in immunology. Understanding the diversity landscape of MHC-I is therefore of paramount importance. The dog is a key translational model in various biomedical fields. However, our understanding of the canine MHC-I diversity landscape lags significantly behind that of humans. To address this deficiency, we used our newly developed software, KPRde novoassembler and genotyper, to genotype 1,325 samples from 1,025 dogs with paired-end RNA-seq data from 43 BioProjects, after extensive quality control. Among 926 dogs that pass the QC, 591 dogs (64%) have at least one allele genotyped, and a total of 97 known alleles and 52 putative new alleles were identified. Further analysis reveals that DLA-I gene expression levels vary among the tissues, with lowest for testis and brain tissues and highest for blood, corpus luteum, and spleen. We identified dominant alleles in each of the 17 canine breeds, as well as among the entire canine population. Furthermore, our analysis also identifies breed-specific alleles and mutually co-occurred/exclusive alleles. Our study indicates that canine DLA-88 is as diversified as human HLA-A/B/C genes within the entire population, but less diversified within a breed than with HLA-A/B/C within an ethnic group. Lastly, we examined the hypervariable regions (HVR) within or across human/canine MHC-I alleles and found that 80% of the HVRs overlap between the two species. We further noted that 80% of the HVRs are within 4A contact with the peptides, and that the dog-human difference overlaps with only 20% HVRs. Our research offers valuable insights for immunological studies involving dogs.