Weighted single step GWAS reveals genomic regions associated with economic traits in Murrah buffaloes.

The objective of the present study was to identify genomic regions influencing economic traits in Murrah buffaloes using weighted single step Genome Wide Association Analysis (WssGWAS). Data on 2000 animals, out of which 120 were genotyped using a double digest Restriction site Associated DNA (ddRAD) sequencing approach. The phenotypic data were collected from NDRI, India, on growth traits, viz., body weight at 6M (month), 12M, 18M and 24M, production traits like 305D (day) milk yield, lactation length (LL) and dry period (DP) and reproduction traits like age at first calving (AFC), calving interval (CI) and first service period (FSP). The biallelic genotypic data consisted of 49353 markers post-quality check. The heritability estimates were moderate to high, low to moderate, low for growth, production, reproduction traits, respectively. Important genomic regions explaining more than 0.5% of the total additive genetic variance explained by 30 adjacent SNPs were selected for further analysis of candidate genes. In this study, 105 genomic regions were associated with growth, 35 genomic regions with production and 42 window regions with reproduction traits. Different candidate genes were identified in these genomic regions, of which important are OSBPL8, NAP1L1 for growth, CNTNAP2 for production and ILDR2, TADA1 and POGK for reproduction traits.

Weighted single-step genome-wide association study and functional enrichment analyses for gastrointestinal nematode resistance traits in Santa Ines sheep.

This study aimed to identify genomic regions, pathways, and putative candidate genes associated with resistance to gastrointestinal nematode in Santa Ines sheep. The phenotypic information comprised 5529 records from 1703 naturally infected animals. After genomic data quality control, 37,511 SNPs from 589 animals were available. The weighted single-step approach for genome-wide association study was performed to estimate the SNP effects and variances accounted by 10-SNP sliding windows. Confirming the polygenic nature of the studied traits, 20, 22, 21, and 19 genomic windows that explained more than 0.5% of the additive genetic variance were identified for fecal egg counts (FEC), Famacha© (FAM), packed cell volume (PCV), and total plasma protein (TPP), respectively. A total of 81, 122, 106, and 101 protein-coding genes were found in windows associated with FEC, FAM, PCV, and TPP, respectively. Several protein-coding genes related to the immune system and inflammatory response functions were identified within those genomic regions, such as ADCY9, ADRB2, BRAF, CADM1, CCL20, CD70, CREBBP, FNBP1, HTR4, IL16, IL22, IL26, MAPK8, NDFIP1, NLRC3, PAK5, PLCB1, PLCB4, ROCK1, TEK, TNFRSF12A, and VAV1. Functional enrichment analysis by DAVID tool also revealed many significant (P < 0.05) pathways and Gene Ontology terms that could be related to resistance to gastrointestinal nematode in Santa Ines sheep, such as chemokine signaling pathway (oas04062), cAMP signaling pathway (oas04024), cGMP-PKG signaling pathway (Oas04022), platelet activation (Oas04611), Rap1 signaling pathway (oas04015), and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705). These results contribute to improving the knowledge of the genetic architecture of resistance to gastrointestinal nematode in Santa Ines sheep.

Investigation of potential genetic factors for growth traits in yellow-feather broilers using weighted single-step genome-wide association study.

Yellow-feather broilers take a large portion of poultry industry in China due to its meat characteristics. Improving the growth traits of yellow-feathered broilers will have great significance for the Chinese poultry market. The current study was designed to investigate the potential genetic factors using the weighted single-step genome-wide association study (wssGWAS) method, which takes consideration of more factors including pedigree, sex, environment and has more accuracy than traditional GWAS. The yellow-feather dwarf chickens from Wens Nanfang Poultry Breeding Co. Ltd. were revolved to recode 9 growth traits: Average daily gain (ADG), body weight (BW) at 45 d, 49 d, 56 d, 63 d, 70 d, 77 d, 84 d, 91 d for analysis. For the results, the region 4.63 to 5.03 Mb on chromosome 15, which was the QTL overlapped in BW45, BW49, BW56, BW63, BW84, might be the crucial genetic region for growth traits. Seven GO terms and 3 KEGG pathways, GO:0005200, GO:0005882, GO:0045111, GO:0099513, GO:0099081, GO:0099512, GO:0099080, KEGG:gga04020, KEGG:gga04540, KEGG:gga04210, were detected to relevant with growth traits. The genes enriched in these biological processes (NRAS, TUBB1, ADORA2B, NTRK3, NGF, TNNC2, F-KER, LOC429492, LOC431325, LOC431324, LOC396480) might have the function in growth of yellow-feather broilers.

Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle.

BACKGROUND: The study of molecular processes regulating heat stress response in dairy cattle is paramount for developing mitigation strategies to improve heat tolerance and animal welfare. Therefore, we aimed to identify quantitative trait loci (QTL) regions associated with three physiological indicators of heat stress response in Holstein cattle, including rectal temperature (RT), respiration rate score (RS), and drooling score (DS). We estimated genetic parameters for all three traits. Subsequently, a weighted single-step genome-wide association study (WssGWAS) was performed based on 3200 genotypes, 151,486 phenotypic records, and 38,101 animals in the pedigree file. The candidate genes located within the identified QTL regions were further investigated through RNA sequencing (RNA-seq) analyses of blood samples for four cows collected in April (non-heat stress group) and four cows collected in July (heat stress group). RESULTS: The heritability estimates for RT, RS, and DS were 0.06, 0.04, and 0.03, respectively. Fourteen, 19, and 20 genomic regions explained 2.94%, 3.74%, and 4.01% of the total additive genetic variance of RT, RS, and DS, respectively. Most of these genomic regions are located in the Bos taurus autosome (BTA) BTA3, BTA6, BTA8, BTA12, BTA14, BTA21, and BTA24. No genomic regions overlapped between the three indicators of heat stress, indicating the polygenic nature of heat tolerance and the complementary mechanisms involved in heat stress response. For the RNA-seq analyses, 2627 genes were significantly upregulated and 369 downregulated in the heat stress group in comparison to the control group. When integrating the WssGWAS, RNA-seq results, and existing literature, the key candidate genes associated with physiological indicators of heat stress in Holstein cattle are: PMAIP1, SBK1, TMEM33, GATB, CHORDC1, RTN4IP1, and BTBD7. CONCLUSIONS: Physiological indicators of heat stress are heritable and can be improved through direct selection. Fifty-three QTL regions associated with heat stress indicators confirm the polygenic nature and complex genetic determinism of heat tolerance in dairy cattle. The identified candidate genes will contribute for optimizing genomic evaluation models by assigning higher weights to genetic markers located in these regions as well as to the design of SNP panels containing polymorphisms located within these candidate genes.

Genome-Wide Association Study Provides Insights into Important Genes for Reproductive Traits in Nelore Cattle.

The identification of genomic regions associated with reproductive traits as well as their biological processes allows a better understanding of the phenotypic variability of these traits. This information could be applied to animal breeding programs to accelerate genetic gain. The aim of this study was to evaluate the association between single nucleotide polymorphisms (SNP) with a scrotal circumference at 365 days of age (SC365) and at 450 days of age (SC450), gestation length (GL) as a calf trait, age at first calving (AFC), accumulated productivity (ACP), heifer early calving until 30 months (HC30), and stayability (STAY) traits, in order to identify candidate genes and biological pathways associated with reproductive traits in Nelore cattle. The data set consisted of pedigree, phenotypes, and genotypes of Nelore cattle from the "Associação Nacional de Criadores e Pesquisadores" (ANCP). The association analyses were performed using the Weighted Single-Step Genome-Wide Association method; the regions, consisting of 10 consecutive SNP, which explained more than 0.5% of additive genetic variance, were considered as a significant association. A total of 3, 6, 7, 5, 10, 25, and 12 windows were associated with SC355, SC450, GL, AFC, ACP, HC30, and STAY, respectively. The results revealed genes with important functions for reproductive traits, such as fertility and precocity. Some genes were associated with more than one trait, among them CAMK1D, TASP1, ACOXL, RAB11FIP5, and SFXN5. Moreover, the genes were enriched in functional terms, like negative regulation of fat cell differentiation, fatty acid alpha-oxidation, and sphingolipids signaling pathway. The identification of the genes associated with the traits, as well as genes enriched in the terms and pathway mentioned above, should contribute to future biological validation studies and may be used as candidate genes in Nelore breeding programs.