Analysis of Hematological Traits in Polled Yak by Genome-Wide Association Studies Using Individual SNPs and Haplotypes

Abstract

Yak (Bos grunniens) is an important domestic animal living in high-altitude plateaus. Due to inadequate disease prevention, each year, the yak industry suffers significant economic losses. The identification of causal genes that affect blood- and immunity-related cells could provide preliminary reference guidelines for the prevention of diseases in the population of yaks. The genome-wide association studies (GWASs) utilizing a single-marker or haplotype method were employed to analyze 15 hematological traits in the genome of 315 unrelated yaks. Single-marker GWASs identified a total of 43 significant SNPs, including 35 suggestive and eight genome-wide significant SNPs, associated with nine traits. Haplotype analysis detected nine significant haplotype blocks, including two genome-wide and seven suggestive blocks, associated with seven traits. The study provides data on the genetic variability of hematological traits in the yak. Five essential genes (GPLD1, EDNRA,APOB, HIST1H1E, and HIST1H2BI) were identified, which affect the HCT, HGB, RBC, PDW, PLT, and RDWSD traits and can serve as candidate genes for regulating hematological traits. The results provide a valuable reference to be used in the analysis of blood properties and immune diseases in the yak.

Keywords: haplotype analysis; hematological traits; polled yak; single-marker GWAS.

Figure 1

A portion of the GWAS results of hematological traits at a significant level in Polled yak. X axis indicates chromosome, Y axis indicates −lg (p-value), the solid line indicates genome-wide significant level and the dashed line indicates the chromosome-wide significance level, the bars below each chromosome are the density of the markers. RBC: red blood cell count. HCT: hematocrit; HGB: hemoglobin; OTHR: medium white blood cell count; PLT: platelet count; MPV: mean platelet volume; PLCR: platelet count; LYM: lymphocyte count; PDW: platelet distribution width.(A–I) Manhattan plot representing HCT, LYM, PDW, HGB, OTHR, PLCR, RBC, MPV and PLT traits, respectively.

Figure 2

Manhattan plots for the haplotype analysis of hematological traits surpass the genome-wide significant threshold. Log 10 (1/p-value) values are shown for all SNPs that passed quality control. The numbers indicate the chromosomes in the genome. The solid line and dotted line denote the Bonferroni-corrected genome-wide and suggestive significant threshold, respectively. SNPs surpassing the genome-wide threshold are highlighted in red and SNPs reaching the suggestive threshold in green. The bars below each chromosome are the density of the markers. E.g., Manhattan of HCT means Manhattan map obtained by haplotype analysis of HCT traits. HCT: hematocrit; RBC: red blood cell count; HGB: hemoglobin; OTHR: medium white blood cell count; PLT: platelet count; RDW-SD: red blood cell volume distribution width-SD; PLCR: platelet count.(A–G) Manhattan plot representing HCT, HGB, OTHR, RBC, PLT, RDWSD and PLCR traits, respectively.