Whole-genome resequencing reveals diversity, global and local ancestry proportions in Yunling cattle.

Yunling cattle, a three-breed cross consisting of 1/2 Brahman cattle, 1/4 Murray Grey cattle and 1/4 Yunnan Yellow cattle, has advantage of rapid growth, good meat quality, enhanced tolerance towards a hot and humid climate, tick resistance and crude feed forbearance. Here, we investigated the genetic diversity, global and local ancestry proportions by sequencing the genomes of 131 Yungling cattle and 31 Brahman cattle (for control). Furthermore, we used 35 published genomes of ancestry breeds (including Angus cattle [ancestry of Murray Grey], Wannan cattle [ancestry of Yunnan Yellow cattle: Wenshan and Dianzhong], Wenshan and Dianzhong cattle) to characterize the formation process of Yunling cattle. The highest nucleotide diversity was found in the Wannan cattle, followed by Wenshan, Dianzhong, Brahman, Yunling and Angus cattle. The results of LD decay in each breed was largely consistent with the results of nucleotide diversity, except for the faster decay in Angus cattle out of a smaller effective population size and a strong bottleneck during the breed formation. The population-structure analysis revealed that the cross-breed Yunling cattle harboured the ancestry with Angus (0.44), Brahman (0.48) and Wannan cattle (0.08). Subsequently, we used RFmix to infer local ancestry in Yunling cattle and then performed chi-squared test to obtain the segments whose proportions of a certain ancestry were excessive compared with the whole-genome level, leading to 391 Angus, 49 Brahman and 2,312 Wannan segments. Gene annotation and KEGG enrichment analysis revealed that the excessive Angus, Brahman and Wannan segments might contribute to the rapid growth, immune resistance and indigenous adaptation, respectively, in Yunling cattle. Our results help understand ancestry components and formation process in Yunling cattle and will provide an opportunity for selective breeding by molecular approaches in future.

Genome-wide association study identifies genomic loci associated with flight reaction in cattle.

Lower flight reaction is closely related to higher production in cattle, but the genetic basis of lower flight reaction is not clearly understood. Here, we sampled a total of 45 Brahman cattles and 166 Yunling cattles with flight distance (FD), and 73 Brahman cattles and 288 Yunling cattles with crush score (CS) and flight speed (FS), whereas there were 45 Brahman cattles and 161 Yunling cattles with all three traits. The FD, CS and FS in Brahman cattle were significantly lower than those in Yunling cattle. The flight reaction traits had negative correlation with conformational traits (e.g., body weight, withers height and body length). Based on SNPs derived from a subset of 162 whole genomes (25 Brahman genomes and 100 Yunling genomes with FD, 30 Brahman and 131 Yunling genomes with CS and FS), genome-wide association study with mixed linear model was performed to test potential associations between flight reaction traits and genomic variants. We identified five, two and two genomic loci suggestively associated with FD, CS and FS, respectively. Five out of five candidate genes for FD (LOC789753, LRP6, CTIF, SLC9A9 and ZEB1) were reported to be related to Alzheimer's disease representing cognitive impairment in human, which was consistent with the finding that cognitive-behavioural intervention decreased the FD of cows to human. In CS, a very strong association locus was assigned to CDH8, a cadherin involved in synaptic adhesion, axon outgrowth and guidance, whose deletion was associated with autism spectrum disorder. In FS, a very strong association locus was assigned to GABRG2, a gamma-aminobutyric acid (a major inhibitory neurotransmitter in brain) receptor, whose polymorphisms were associated with suicidal behaviour in schizophrenia patients. Our findings will provide targets for molecular-marker selection and genetic manipulation of cattle improvement to meeting the growing demand for lower flight reaction to human.

Genome-wide association study identifies quantitative trait loci affecting cattle temperament.

Cattle temperament is an interesting trait due to its correlation with production efficiency, labor safety, and animal welfare. To date, however, its genetic basis is not clearly understood. Here, we performed a genome-wide association study for a series of temperament traits in cattle, assessed with via open field and novel object tests, using autosomal single nucleotide polymorphisms (SNPs) derived from the whole-genome sequence. We identified 37 and 29 genome-wide significant loci in the open field and novel object tests, respectively. Gene set analysis revealed the most significant pathway was the neuroactive ligand-receptor interaction pathway, which may be essential for emotional control in cattle. Analysis of the expression levels of 18 tissue-specific genes based on transcriptomic data showed enrichment in the brain, with some candidate genes involved in psychiatric and neurodegenerative diseases in humans. Based on principal component analysis, the first principal component explained the largest variance in the open field and novel object test data, and the most significant loci were assigned to SORCS3 and SESTD1, respectively. Our findings should help facilitate cattle breeding for sound temperament by pyramiding favorable alleles to further improve cattle production.

Whole-genome analyses identify loci and selective signals associated with body size in cattle.

Body size plays a key role in production, health, selection, and environmental adaptation of animals, but the genetic basis of body size variation is not clearly understood. Here, we conducted genome-wide association studies (GWAS) of 15 body size traits using autosomal single nucleotide polymorphisms (SNPs) derived from whole-genome sequences of 31 Brahman cattle and 131 Yunling cattle and identified 20 significant loci, which implicated 18 candidate genes. For ischium width, the most significant SNP was assigned to LCORL, a famous gene controlling body size. For chest width, the most significant SNP was located upstream of BMP5, a secreted ligand of transformation growth factor-beta superfamily of proteins involved in bone and cartilage development. Subsequently, we detected selective sweeps in Brahman cattle using integrated Haplotype Score, composite likelihood ratio, and nucleotide diversity. The results showed CNTNAP5 locus associated with hip cross height and LIMCH1 locus associated with forehead size were in selective signals, which were consistent with higher hip cross height and higher forehead size in Brahman cattle compared with Yunling cattle. Our findings provide genetic insights into variation and selection of body size using GWAS and selective signals and will accelerate future efforts aimed at cattle improvement.

Genome-Wide Association Study Identifies Genomic Loci Associated With Neurotransmitter Concentration in Cattle.

Abnormal neurotransmitter concentration is one of the factors that affect the health status, behavioral personality, and welfare level of animals, but the genetic basis of the abnormality is still largely unknown. The objective of this study is to identify putative genomic loci associated with neurotransmitter concentration in cattle. We measured serotonin (5HT), dopamine (DA), cortisol, glutamate (Glu), and ACTH concentrations in blood serum using double-antibody sandwich ELISA in 30 Brahman cattle and 127 Yunling cattle. Interestingly, we found that ACTH concentration was positively correlated with body weight, cannon circumference, and hip width (P < 0.05). Genome-wide association study (GWAS) was performed with mixed linear models using autosomal SNPs derived from the whole-genome sequence. We identified five, five, two, three, and five suggestive loci associated with 5HT, DA, cortisol, Glu, and ACTH concentration, respectively. These 20 associated loci implicated 18 candidate genes. For Glu concentration, the most significant association locus was assigned to MCHR1, a G-coupled receptor that could modulate glutamate release. For dopamine concentration, a very strong association locus was located in the intron of SLC18A2, which is a critical mediator of dopamine dynamics. However, for ACTH concentration, a very strong association locus was assigned to HTR1F, a G protein-coupled receptor that can influence the release of ACTH. Other candidate genes of interest identified for neurotransmitter concentration were PRMT6, GADD45A, PCCA, ANGPT1, ACCS, LOC100336971, TNR, GSDMA, CNTN3, CARMIL1, CDKAL1, RBFOX1, PCDH15, and LGALS12. Our findings will provide targets for the genetic improvement of neurotransmitter-related traits in domestic cattle and basic materials for studying the mechanism of neurotransmitter synthesis, release, and transport in human and animals.