4.3 Article

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

Journal

IMMUNOGENETICS
Volume 74, Issue 2, Pages 245-259

Publisher

SPRINGER
DOI: 10.1007/s00251-021-01234-5

Keywords

Major histocompatibility complex; MHC; Dog leukocyte antigen; DLA; Recombination; Gene conversion; Haplotypes

Funding

  1. Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Japan [S1491007]

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By analyzing the DNA sequences of the DLA class I genomic region in dogs, this study discovered that DLA-88L is a hybrid gene formed by interlocus and/or intralocus gene conversion between DLA-88 and DLA-12. It was also found that at least one DLA-12 allele is generated through interlocus gene conversion. These findings suggest that intralocus gene conversion plays an important role in expanding DLA allelic variations.
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.

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