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由基因内和基因间重组事件塑造的犬白细胞抗原(DLA)I 类基因座的单体型结构和多态性。

Haplotype structures and polymorphisms of dog leukocyte antigen (DLA) class I loci shaped by intralocus and interlocus recombination events.

机构信息

Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoino-oka, Imabari, Ehime, 794-8555, Japan.

Department of Legal Medicine, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan.

出版信息

Immunogenetics. 2022 Apr;74(2):245-259. doi: 10.1007/s00251-021-01234-5. Epub 2022 Jan 7.

DOI:10.1007/s00251-021-01234-5
PMID:34993565
Abstract

The dog leukocyte antigen (DLA) class I genomic region is located on chromosome 12, and the class I genomic region is composed of at least two distinct haplotypic gene structures, DLA-88-DLA-12 and DLA-88-DLA-88L. However, detailed information of the genomic differences among DLA-88, DLA-12, and DLA-88L are still lacking at the full-length gene level, and therefore, DLA allelic sequences classified for each of these loci are limited in number so far. In this study, we determined the DNA sequence of a 95-kb DLA class I genomic region including DLA-88, DLA-12/88L, and DLA-64 with three DLA homozygous dogs and of 37 full-length allelic gene sequences for DLA-88 and DLA-12/88L loci in 26 DLA class I homozygous dogs. Nucleotide diversity profiles of the 95-kb regions and sequence identity scores of the allelic sequences suggested that DLA-88L is a hybrid gene generated by interlocus and/or intralocus gene conversion between DLA-88 and DLA-12. The putative minimum conversion tract was estimated to be at least an 850-bp segment in length located from the 5´flanking untranslated region to the end of intron 2. In addition, at least one DLA-12 allele (DLA-12*004:01) was newly generated by interlocus gene conversion. In conclusion, the analysis for the occurrence of gene conversion within the dog DLA class I region revealed intralocus gene conversion tracts in 17 of 27 DLA-88 alleles and two of 10 DLA-12 alleles, suggesting that intralocus gene conversion has played an important role in expanding DLA allelic variations.

摘要

犬白细胞抗原 (DLA) I 类基因组区域位于染色体 12 上,I 类基因组区域由至少两种不同的单倍型基因结构组成,即 DLA-88-DLA-12 和 DLA-88-DLA-88L。然而,在全长基因水平上,DLA-88、DLA-12 和 DLA-88L 之间的基因组差异的详细信息仍然缺乏,因此,到目前为止,这些基因座分类的 DLA 等位基因序列数量有限。在这项研究中,我们使用三只 DLA 纯合犬确定了一个包含 DLA-88、DLA-12/88L 和 DLA-64 的 95-kb DLA I 类基因组区域的 DNA 序列,并在 26 只 DLA I 类纯合犬中确定了 37 个 DLA-88 和 DLA-12/88L 基因座的全长等位基因序列。95-kb 区域的核苷酸多样性分布和等位基因序列的序列同一性评分表明,DLA-88L 是 DLA-88 和 DLA-12 之间的基因间和/或基因内基因转换产生的杂种基因。推测的最小转换片段至少有 850 个碱基对长,位于 5´侧翼非翻译区到内含子 2 末端。此外,至少一个 DLA-12 等位基因 (DLA-12*004:01) 是由基因间基因转换产生的。总之,对犬 DLA I 类区域内基因转换的分析表明,在 27 个 DLA-88 等位基因中有 17 个和 10 个 DLA-12 等位基因中有 2 个发生了基因内转换,这表明基因内转换在扩大 DLA 等位基因变异方面发挥了重要作用。

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