Complex variation in the KLRA (LY49) immunity-related genomic region in horses.

Jan Futas, Jan Oppelt, Eva Janova, Petra Musilova, Petr Horin

HLA 2020 Sep

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Natural killer (NK) cells play important roles in innate and adaptive immunity, as well as in the reproduction of placental mammals. Ly49 (KLRA) molecules represent a lectin-like type of NK cell receptor encoded within a complex genomic region, the NK cell complex. In rodents and horses, an expansion of the genes encoding Ly49 receptors leading to the formation of a gene family was observed. High sequence similarities and frequent high polymorphism of multiple family members represent an obstacle both for their individual identification and for annotation in the reference genomes of their respective species. Here, we focused on resolving complex variation of the KLRA gene family observed in domestic and Przewalski's horses. The KLRA (LY49) genomic region contains six genes (KLRA2-KLRA7) and one putative pseudogene, KLRA1. Two types of polymorphism were observed in the horses analyzed. Copy number variation between haplotypes was documented for the gene KLRA7 by polymerase chain reaction. As expected, the major source of variation of all KLRA genes, including KLRA7, is because of single nucleotide polymorphisms, many of them being nonsynonymous substitutions. Extensive allelic variability of the expanded KLRA (LY49) genes was observed. For four out of the six functional KLRA, high numbers of novel allelic amino acid sequence variants were identified in the genes studied, suggesting that this variation might be of functional importance, especially in the context of high polymorphism of their presumed ligands encoded by major histocompatibility complex class I genes. In fact, polymorphic amino acid sites were mostly found in the ligand-binding C-type lectin-like domain of the putative receptor molecule. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Citation

Jan Futas, Jan Oppelt, Eva Janova, Petra Musilova, Petr Horin. Complex variation in the KLRA (LY49) immunity-related genomic region in horses. HLA. 2020 Sep;96(3):257-267