Identification of Whole-Genome Significant Single Nucleotide Polymorphisms in Candidate Genes Associated With Serum Biochemical Traits in Chinese Holstein Cattle

Abstract

A genome-wide association study (GWAS) was conducted on 23 serum biochemical traits in Chinese Holstein cattle. The experimental population consisted of 399 cattle, each genotyped by a commercial bovine 50K SNP chip, which had 49,663 SNPs. After data cleaning, 41,092 SNPs from 361 Holstein cattle were retained for GWAS. The phenotypes were measured values of serum measurements of these animals that were taken at 11 days after parturition. Two statistical models, a fixed-effect linear regression model (FLM) and a mixed-effect linear model (MLM), were used to estimate the association effects of SNPs. Genome-wide significant and suggestive thresholds were set up to be 1.22E−06 and 2.43E−06, respectively. In the Chinese Holstein population, FLM identified 81 genome-wide significant (0.05/41,092 = 1.22E−06) SNPs associated with 11 serum traits. Among these SNPs, five SNPs (BovineHD0100005950, ARS-BFGL-NGS-115158, BovineHD1500021175, BovineHD0800028900, and BTB-00442438) were also identified by the MLM to have genome-wide suggestive effects on CHE, DBIL, and LDL. Both statistical models pinpointed two SNPs that had significant effects on the Holstein population. The SNP BovineHD0800028900 (located near the gene LOC101903458 on chromosome 8) was identified to be significantly associated with serum high-and low-density lipoprotein (HDL and LDL), whereas BovineHD1500021175 (located in 73.4Mb on chromosome 15) was an SNP significantly associated with total bilirubin and direct bilirubin (TBIL and DBIL). Further analyses are needed to identify the causal mutations affecting serum traits and to investigate the correlation of effects for loci associated with fatty liver disease in dairy cattle.

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease

“…The biopsied dairy cattle had their fatty liver condition diagnosed according to the average percentage of hepatic cells containing lipid droplets in the tissue, and other background information of these cows including production and serum biochemical indexes [1,60] was shown in Table S2. As a result, six samples were diagnosed as normal liver (6.26 ± 5.23%) and eight as severe fatty liver (86.75 ± 4.83%).…”

“…More than 60% of dairy cows develop fatty liver during the transition period from dry milk to lactation due to negative energy imbalance [1], resulting in weakened liver function and decreased milk production [2]. The fatty liver disease in dairy cows is a typical type of nonalcoholic fatty liver disease (NAFLD), mainly caused by obesity and stress response.…”

Identification of Crucial Genetic Factors, Such as PPARγ, that Regulate the Pathogenesis of Fatty Liver Disease in Dairy Cows Is Imperative for the Sustainable Development of Dairy Industry

“…The etiology of fatty liver in perinatal dairy cows primarily includes the negative nutrient balance and the accumulation of high level of free fatty acids (FFA) in serum or triglycerides (TAG) deposited in liver [1]. Liver, the central organ of organisms, regulates the metabolic balance of carbohydrate, fat, and protein in mammals [13].…”

“…Our investigation in the last three years indicated that 48.85% of dairy cows (n = 346) within 2 weeks after parturition were diagnosed with light or severe fatty liver disease by randomly selecting 710 Holstein dairy cows from four commercial farms (Zhang et al, unpublished data) [1,2]. The suspected fatty liver cows and/or normal cows were firstly distinguished by applying the previously reported model [3] using the detected values of serum biochemical traits (glucose, Glu; non-esterified fatty acid, NEFA; aspartate transaminase, AST), then representative cows with different suspected extents were biopsied for liver tissue samples for fat deposition amount assessment by oil red staining.…”

“…However, these strategies cannot either completely change the situation or alleviate contradictions. The incidence of fatty liver disease at the early lactation not only decreases the milk yield of the coming lactation period, but also attenuates the future milk production and reproduction performance because of subsequent health problems of dairy herds [1,2,7,12], such as ketosis, displaced abomasum, mastitis, etc. It is estimated that economic losses due to the treatment of and reduction in milk production by one dairy cow with ketosis accounts for 151-312 US dollars [11].…”