A Multibreed Genome-Wide Association Study for Cattle Leukocyte Telomere Length

Telomeres are terminal DNA regions of chromosomes that prevent chromosomal fusion and degradation during cell division. In cattle, leukocyte telomere length (LTL) is associated with longevity, productive lifespan, and disease susceptibility. However, the genetic basis of LTL in this species is less studied than in humans. In this study, we utilized the whole-genome resequencing data of 239 animals from 17 cattle breeds for computational leukocyte telomere length estimation and subsequent genome-wide association study of LTL. As a result, we identified 42 significant SNPs, of which eight were found in seven genes (EXOC6B, PTPRD, RPS6KC1, NSL1, AGBL1, ENSBTAG00000052188, and GPC1) when using covariates for two major breed groups (Turano-Mongolian and European). Association analysis with covariates for breed effect detected 63 SNPs, including 13 in five genes (EXOC6B, PTPRD, RPS6KC1, ENSBTAG00000040318, and NELL1). The PTPRD gene, demonstrating the top signal in analysis with breed effect, was previously associated with leukocyte telomere length in cattle and likely is involved in the mechanism of alternative lengthening of telomeres. The single nucleotide variants found could be tested for marker-assisted selection to improve telomere-length-associated traits.