Using expression data to fine map QTL associated with fertility in dairy cattle.

BACKGROUND: Female fertility is an important trait in dairy cattle. Identifying putative causal variants associated with fertility may help to improve the accuracy of genomic prediction of fertility. Combining expression data (eQTL) of genes, exons, gene splicing and allele specific expression is a promising approach to fine map QTL to get closer to the causal mutations. Another approach is to identify genomic differences between cows selected for high and low fertility and a selection experiment in New Zealand has created exactly this resource. Our objective was to combine multiple types of expression data, fertility traits and allele frequency in high- (POS) and low-fertility (NEG) cows with a genome-wide association study (GWAS) on calving interval in Australian cows to fine-map QTL associated with fertility in both Australia and New Zealand dairy cattle populations. RESULTS: Variants that were significantly associated with calving interval (CI) were strongly enriched for variants associated with gene, exon, gene splicing and allele-specific expression, indicating that there is substantial overlap between QTL associated with CI and eQTL. We identified 671 genes with significant differential expression between POS and NEG cows, with the largest fold change detected for the CCDC196 gene on chromosome 10. Our results provide numerous candidate genes associated with female fertility in dairy cattle, including GYS2 and TIGAR on chromosome 5 and SYT3 and HSD17B14 on chromosome 18. Multiple QTL regions were located in regions with large numbers of copy number variants (CNV). To identify the causal mutations for these variants, long read sequencing may be useful. CONCLUSIONS: Variants that were significantly associated with CI were highly enriched for eQTL. We detected 671 genes that were differentially expressed between POS and NEG cows. Several QTL detected for CI overlapped with eQTL, providing candidate genes for fertility in dairy cattle.

Genome-wide association study of growth curve parameters reveals novel genomic regions and candidate genes associated with metatarsal bone traits in chickens.

The growth and development of chicken bones have an enormous impact on the health and production performance of chickens. However, the development pattern and genetic regulation of the chicken skeleton are poorly understood. This study aimed to evaluate metatarsal bone growth and development patterns in chickens via non-linear models, and to identify the genetic determinants of metatarsal bone traits using a genome-wide association study (GWAS) based on growth curve parameters. Data on metatarsal length (MeL) and metatarsal circumference (MeC) were obtained from 471 F2 chickens (generated by crossing broiler sires, derived from a line selected for high abdominal fat, with Baier layer dams) at 4, 6, 8, 10, and 12 weeks of age. Four non-linear models (Gompertz, Logistic, von Bertalanffy, and Brody) were used to fit the MeL and MeC growth curves. Subsequently, the estimated growth curve parameters of the mature MeL or MeC (A), time-scale parameter (b), and maturity rate (K) from the non-linear models were utilized as substitutes for the original bone data in GWAS. The Logistic and Brody models displayed the best goodness-of-fit for MeL and MeC, respectively. Single-trait and multi-trait GWASs based on the growth curve parameters of the Logistic and Brody models revealed 4 618 significant single nucleotide polymorphisms (SNPs), annotated to 332 genes, associated with metatarsal bone traits. The majority of these significant SNPs were located on Gallus gallus chromosome (GGA) 1 (167.433-176.318 Mb), GGA2 (96.791-103.543 Mb), GGA4 (65.003-83.104 Mb) and GGA6 (64.685-95.285 Mb). Notably, we identified 12 novel GWAS loci associated with chicken metatarsal bone traits, encompassing 35 candidate genes. In summary, the combination of single-trait and multi-trait GWASs based on growth curve parameters uncovered numerous genomic regions and candidate genes associated with chicken bone traits. The findings benefit an in-depth understanding of the genetic architecture underlying metatarsal growth and development in chickens.

Genetic Background of Blood ß-Hydroxybutyrate Acid Concentrations in Early-Lactating Holstein Dairy Cows Based on Genome-Wide Association Analyses.

Ketosis is a common metabolic disorder in the early lactation of dairy cows. It is typically diagnosed by measuring the concentration of ß-hydroxybutyrate (BHB) in the blood. This study aimed to estimate the genetic parameters of blood BHB and conducted a genome-wide association study (GWAS) based on the estimated breeding value. Phenotypic data were collected from December 2019 to August 2023, comprising blood BHB concentrations in 45,617 Holstein cows during the three weeks post-calving across seven dairy farms. Genotypic data were obtained using the Neogen Geneseek Genomic Profiler (GGP) Bovine 100 K SNP Chip and GGP Bovine SNP50 v3 (Illumina Inc., San Diego, CA, USA) for genotyping. The estimated heritability and repeatability values for blood BHB levels were 0.167 and 0.175, respectively. The GWAS result detected a total of ten genome-wide significant associations with blood BHB. Significant SNPs were distributed in Bos taurus autosomes (BTA) 2, 6, 9, 11, 13, and 23, with 48 annotated candidate genes. These potential genes included those associated with insulin regulation, such as INSIG2, and those linked to fatty acid metabolism, such as HADHB, HADHA, and PANK2. Enrichment analysis of the candidate genes for blood BHB revealed the molecular functions and biological processes involved in fatty acid and lipid metabolism in dairy cattle. The identification of novel genomic regions in this study contributes to the characterization of key genes and pathways that elucidate susceptibility to ketosis in dairy cattle.

The effects of case/control ratio and sample size on genome-wide association studies: A simulation study.

BACKGROUND: Genome-wide association studies (GWAS) is a useful tool for the detection of disease or quantitative trait-related genetic variations in the veterinary field. For a binary trait, a case/control experiment is designed in GWAS. However, there is limited information on the optimal case/control and sample size in GWAS. OBJECTIVES: In this study, it was aimed to detect the effects of case/control ratio and sample size for GWAS using computer simulation under certain assumptions. METHOD: Using the PLINK software, we simulated three different disease scenarios. In scenario 1, we simulated 10 different case/control ratios with increasing ratio of cases to controls. In scenario 2, we did versa of scenario 1 with the increasing ratio of controls to cases. In scenarios 1 and 2, sample size gradually was increased with the change case/control ratios. In scenario 3, the total sample size was fixed to 2000 to see real effects of case/control ratio on the number of disease-related single nucleotide polymorphisms (SNPs). RESULTS: The results showed that the number of disease-related SNPs were the highest when the case/control ratio is close to 1:1 in scenarios 1 and 2 and did not change with an increase in sample size. Similarly, the number of disease-related SNPs was the highest in case/control ratios 1:1 in scenario 3. However, unbalanced case/control ratio caused the detection of lower number of disease-related SNPs in scenario 3. The estimated average power of SNPs was highest when case/control ratio is 1:1 in all scenarios. CONCLUSIONS: All findings led to the conclusion that an increase in sample size may enhance the statistical power of GWAS when the number of cases is small. In addition, case/control ratio 1:1 may be the optimal ratio for GWAS. These findings may be valuable not only for veterinary field but also for human clinical experiments.

A novel QTL region for pH and meat color in Duroc pigs.

One of the most important processes that occur during the transformation of muscle to meat is the pH decline as a consequence of the post-mortem metabolism of muscle tissue. Abnormal pH declines lead to pork defects such as pale, soft, and exudative meat. There is genetic variance for ultimate pH and the role of some genes on this phenotype is well established. After conducting a genome-wide association study on ultimate pH using 526 purebred Duroc pigs, we identified associated regions on Sus scrofa chromosomes (SSC) 3, 8, and 15. Functional candidate genes in these regions included PRKAG3 and PHKG1. The SSC8 region, at 71.6 Mb, was novel and, although no candidate causative gene could be identified, it may have regulatory effects. Subsequent analysis on 828 pigs from the same population confirmed the impact of the three associated regions on pH and meat color. We detected no interaction between the three regions. Further investigations are necessary to unravel the functional significance of the novel genomic region at SSC8. These variants could be used as markers in marker-assisted selection for improving meat quality.

Identification of candidate genes associated with milk production and mastitis based on transcriptome-wide association study.

Genetic research for the assessment of mastitis and milk production traits simultaneously has a long history. The main issue that arises in this context is the known existence of a positive correlation between the risk of mastitis and lactation performance due to selection. The transcriptome-wide association study (TWAS) approach endeavors to combine the expression quantitative trait loci and genome-wide association study summary statistics to decode complex traits or diseases. Accordingly, we used the farmgtex project results as a complete bovine database for mastitis and milk production. The results of colocalization and TWAS approaches were used for the detection of functional associated candidate genes with milk production and mastitis traits on multiple tissue-based transcriptome records. Also, we used the david database for gene ontology to identify significant terms and associated genes. For the identification of interaction networks, the genemania and string databases were used. Also, the available z-scores in TWAS results were used for the calculation of the correlation between tissues. Therefore, the present results confirm that LYNX1, DGAT1, C14H8orf33, and LY6E were identified as significant genes associated with milk production in eight, six, five, and five tissues, respectively. Also, FBXL6 was detected as a significant gene associated with mastitis trait. CLN3 and ZNF34 genes emerged via both the colocalization and TWAS approaches as significant genes for milk production trait. It is expected that TWAS and colocalization can improve our perception of the potential health status control mechanism in high-yielding dairy cows.

Genome-wide association study identifies a novel candidate gene for egg production traits in chickens.

Qingyuan partridge chicken is a renowned indigenous yellow broiler breed in China. Egg production traits are important economic traits for chickens. With the decreasing cost of whole genome resequencing, identifying candidate genes with more precision has become possible. In order to identify molecular markers and candidate genes associated with egg production traits, we conducted genome-wide association studies based on the resequencing data of 287 female Qingyuan partridge chickens. For each hen, age at first egg and egg laying rate were recorded and calculated, respectively. With a univariate linear mixed model, we detected one genome-wide significant single nucleotide polymorphism (SNP) and three chromosome-wide significant SNPs associated with egg laying rate. MTA2 is highly likely to be a functional gene for egg laying rate. Our study identifies MTA2 as the first time to be associated with egg laying rate. Findings in our study will advance our understanding of the genetic basis of egg production and have the potential to improve the efficiency of genomic selection in chickens.

Genome-wide association study identified five quantitative trait loci and two candidate genes for digestive traits in Suhuai pigs.

This work aimed to identify markers and candidate genes underlying porcine digestive traits. In total, 331 pigs were genotyped by 80 K Chip data or 50 K Chip data. For apparent neutral detergent fiber digestibility, a total of 19 and 21 candidate single nucleotide polymorphisms (SNP) were respectively identified using a genome-wide efficient mixed-model association algorithm and linkage-disequilibrium adjusted kinship. Among them, three quantitative trait locus (QTL) regions were identified. For apparent acid detergent fiber digestibility, a total of 16 and 17 SNPs were identified by these two methods, respectively. Of these, three QTL regions were also identified. Moreover, two candidate genes (MST1 and LATS1), which are functionally related to intestinal homeostasis and health, were detected near these significant SNPs. Taken together, our results could provide a basis for deeper research on digestive traits in pigs.

Genomic insights into shank and eggshell color in Italian local chickens.

Eggshell and shank color in poultry is an intriguing topic of research due to the roles in selection, breed recognition, and environmental adaptation. This study delves into the genomics foundations of shank and eggshell pigmentation in Italian local chickens through genome-wide association studies analysis to uncover the mechanisms governing these phenotypes. To this purpose, 483 animals from 20 local breeds (n = 466) and 2 commercial lines (n = 17) were considered and evaluated for shank and eggshell color. All animals were genotyped using the Affymetrix Axiom 600 K Chicken Genotyping Array. As regards shank color, the most interesting locus was detected on chromosome Z, close to the TYRP1 gene, known to play a key role in avian pigmentation. Additionally, several novel loci and genes associated with shank pigmentation, skin pigmentation, UV protection, and melanocyte regulation were identified (e.g., MTAP, CDKN2A, CDKN2B). In eggshell, fewer significant loci were identified, including SLC7A11 and MITF on chromosomes 4 and 12, respectively, associated with melanocyte processes and pigment synthesis. This comprehensive study shed light on the genetic architecture underlying shank and eggshell color in Italian native chicken breeds, contributing to a better understanding of this phenomenon which plays a role in breed identification and conservation, and has ecological and economic implications.

Genetic parameter estimation and molecular foundation of chicken egg-laying trait.

The age of first egg (AFE) in chicken can affect early and even life-time egg production performance to some extent, and therefore is an important economic trait that affects production efficiency. To better understand the genetic patterns of AFE and other production traits including body weight at first egg (BWA), first egg weight (FEW), and total egg number from AFE to 58 wk of age (total-EN), we recorded the production performance of 2 widely used layer breeds, white leghorn (WL) and Rhode Island Red (RIR) and estimated genetic parameters based on pedigree and production data. The results showed that the heritability of AFE in both breeds ranged from 0.4 to 0.6, and AFE showed strong positive genetic and phenotypic correlations to BWA as well as FEW, while showing strong negative genetic and phenotypic correlations with total-EN. Furtherly, by genome-wide association analysis study (GWAS), we identified 12 and 26 significant SNPs to be related to AFE in the 2-layer breeds, respectively. A total of 18 genes were identified that could affect AFE based on the significant SNP annotations obtained, but there were no gene overlapped in the 2 breeds indicating the genetic foundation of AFE could differ from breed to breed. Our results provided a deeper understanding of genetic patterns and molecular basement of AFE in different breeds and could help in the selection of egg production traits.

Genome-wide association studies of egg production traits by whole genome sequencing of Laiwu Black chicken.

Compared to high-yield commercial laying hens, Chinese indigenous chicken breeds have poor egg laying capacity due to the lack of intensive selection. However, as these breeds have not undergone systematic selection, it is possible that there is a greater abundance of genetic variations related to egg laying traits. In this study, we assessed 5 egg number (EN) traits at different stages of the egg-laying period: EN1 (from the first egg to 23 wk), EN2 (from 23 to 35 wk), EN3 (from 35 to 48 wk), EN4 (from the first egg to 35 wk), and EN5 (from the first egg to 48 wk). To investigate the molecular mechanisms underlying egg number traits in a Chinese local chicken breed, we conducted a genome-wide association study (GWAS) using data from whole-genome sequencing (WGS) of 399 Laiwu Black chickens. We obtained a total of 3.01 Tb of raw data with an average depth of 7.07 × per individual. A total of 86 genome-wide suggestive or significant single-nucleotide polymorphisms (SNP) contained within a set of 45 corresponding candidate genes were identified and found to be associated with stages EN1-EN5. The genes vitellogenin 2 (VTG2), lipase maturation factor 1 (LMF1), calcium voltage-gated channel auxiliary subunit alpha2delta 3 (CACNA2D3), poly(A) binding protein cytoplasmic 1 (PABPC1), programmed cell death 11 (PDCD11) and family with sequence similarity 213 member A (FAM213A) can be considered as the candidate genes associated with egg number traits, due to their reported association with animal reproduction traits. Noteworthy, results suggests that VTG2 and PDCD11 are not only involved in the regulation of EN3, but also in the regulation of EN5, implies that VTG2 and PDCD11 have a significant influence on egg production traits. Our study offers valuable genomic insights into the molecular genetic mechanisms that govern egg number traits in a Chinese indigenous egg-laying chicken breed. These findings have the potential to enhance the egg-laying performance of chickens.

Molecular genetic foundation of a sex-linked tailless trait in Hongshan chicken by whole genome data analysis.

As a Chinese local chicken breed, Hongshan chickens have 2 kinds of tail feather phenotypes, normal and taillessness. Our previous studies showed that taillessness was a sex-linked dominant trait. Abnormal development of the tail vertebrae could be explained this phenomenon in some chicken breeds. However, the number of caudal vertebrae in rumpless Hongshan chickens was normal, so rumplessness in Hongshan chicken was not related to the development of the caudal vertebrae. Afterwards, we found that rumplessness in Hongshan was due to abnormal development of tail feather rather than abnormal development of caudal vertebrae. In order to understand the genetic foundation of the rumplessness of Hongshan chickens, we compared and reanalyzed 2 sets of data in normal and rumpless Hongshan chickens from our previous studies. By joint analysis of genome-wide selection signature analysis and genome-wide association approach, we found that 1 overlapping gene (EDIL3) and 16 peak genes (ENSGALG00000051843, ENSGALG00000053498, ENSGALG00000054800, KIF27, PTPRD, ENSGALG00000047579, ENSGALG00000041052, ARHGEF28, CAMK4, SERINC5, ENSGALG00000050776, ERCC8, MCC, ADAMTS19, ENSGALG00000053322, CHRNA8) located on the Z chromosome was associated with the rumpless trait. The results of this study furtherly revealed the molecular mechanism of the rumpless trait in Hongshan chickens, and identified the candidate genes associated with this trait. Our results will help to improve the shape of chicken tail feathers and to rise individual economic value in some specific market in China.

Whole genome resequencing reveals genomic regions related to red plumage in ducks.

Plumage color is a characteristic trait of ducks that originates as a result of natural and artificial selection. As a conspicuous phenotypic feature, it is a breed characteristic. Previous studies have identified some genes associated with the formation of black and white plumage in ducks. However, studies on the genetic basis underlying the red plumage phenotype in ducks are limited. Here, genome-wide association analysis (GWAS) and selection signal detection (Fst, θπ ratio, and cross-population composite likelihood ratio [XP-CLR]) were conducted to identify candidate regions and genes underlying duck plumage color phenotype. Selection signal detection revealed 29 overlapping genes (including ENPP1 and ULK1) significantly associated with red plumage color in Ji'an Red ducks. ENSAPLG00000012679, ESRRG, and SPATA5 were identified as candidate genes associated with red plumage using GWAS. Selection signal detection revealed that 19 overlapping genes (including GMDS, PDIA6, and ODC1) significantly correlated with light brown plumage in Brown Tsaiya ducks. GWAS to narrow down the significant regions further revealed nine candidate genes (AKT1, ATP6V1C2, GMDS, LRP4, MAML3, PDIA6, PLD5, TMEM63B, and TSPAN8). Notably, in Brown Tsaiya ducks, GMDS, ODC1, and PDIA6 exhibit significantly differentiated allele frequencies among other feather-colored ducks, while in Ji'an Red ducks, ENSAPLG00000012679 has different allele frequency distributions compared with that in other feather-colored ducks. This study offers new insights into the variation and selection of the red plumage phenotype using GWAS and selective signals.

Genome-wide association studies of anserine and carnosine contents in the breast meat of Korean native chickens.

Histidine-containing dipeptides (HCDs), such as anserine and carnosine, are enormously beneficial to human health and contribute to the meat flavor in chickens. Meat quality traits, including flavor, are polygenic traits with medium to high heritability. Polygenic traits can be improved through a better understanding of their genetic mechanisms. Genome-wide association studies (GWAS) constitute an effective genomic tool to identify the significant single-nucleotide polymorphisms (SNPs) and potential candidate genes related to various traits of interest in chickens. This study identified potential candidate genes influencing the anserine and carnosine contents in chicken meat through GWAS. We performed GWAS of anserine and carnosine using the Illumina chicken 60K SNP chip (Illumina Inc., San Diego, CA) in 637 Korean native chicken-red-brown line (KNC-R) birds consisting of 228 males and 409 females. The contents of anserine and carnosine in breast meat of KNC-R chickens were investigated. The mean value of the anserine and carnosine are 29.12 mM/g and 10.69 mM/g respectively. The genomic heritabilities were moderate (0.24) for anserine and high (0.43) for carnosine contents. Four and nine SNPs were significantly (P < 0.05) associated with anserine and carnosine, respectively. Based on the GWAS result, the 30.6 to 31.9 Mb region on chicken chromosome 7 was commonly associated with both anserine and carnosine. Through the functional annotation analysis, we identified HNMT and HNMT-like genes as potential candidate genes associated with both anserine and carnosine. The results presented here will contribute to the ongoing improvement of meat quality to satisfy current consumer demands, which are based on healthier, better-flavored, and higher-quality chicken meat.

Genome-wide association study for bone quality of ducks during the laying period.

The cage-rearing model of the modern poultry industry makes the bones of birds, especially egg-laying birds, more vulnerable to fracture, which poses serious damage to the health of birds. Research confirms that genetic material plays an important role in regulating bone growth, development, and remodeling. However, the genetic architecture underlying bone traits is not well understood. The objectives of this study are to identify valuable genes and genetic markers through a genome-wide association study (GWAS) for breeding to improve the duck bone quality. First, we quantified the tibia and femur quality traits of 260 laying ducks. Based on GWAS, a total of 75 SNP loci significantly associated with bone quality traits were identified, and 67 potential candidate genes were annotated. According to gene function analysis, genes P4HA2, WNT3A, and BST1 et al may influence bone quality by regulating bone cell activity, calcium and phosphate metabolism, or bone collagen maturation and cross-linking. Meanwhile, combined with the transcriptome results, we found that HOXB cluster genes are also important in bone growth and development. Therefore, our findings were helpful in further understanding the genetic architecture of the duck bone quality and provided a worthy theoretical basis and technological support to improve duck bone quality by breeding.

Deciphering the population structure and genetic basis of growth traits from whole-genome resequencing of the leopard coral grouper ( Plectropomus leopardus).

The leopard coral grouper ( Plectropomus leopardus) is a species of significant economic importance. Although artificial cultivation of P. leopardus has thrived in recent decades, the advancement of selective breeding has been hindered by the lack of comprehensive population genomic data. In this study, we identified over 8.73 million single nucleotide polymorphisms (SNPs) through whole-genome resequencing of 326 individuals spanning six distinct groups. Furthermore, we categorized 226 individuals with high-coverage sequencing depth (≥14×) into eight clusters based on their genetic profiles and phylogenetic relationships. Notably, four of these clusters exhibited pronounced genetic differentiation compared with the other populations. To identify potentially advantageous loci for P. leopardus, we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity ( θπ) and fixation index ( F ST) in these four clusters. Using these high-coverage resequencing data, we successfully constructed the first haplotype reference panel specific to P. leopardus. This achievement holds promise for enabling high-quality, cost-effective imputation methods. Additionally, we combined low-coverage sequencing data with imputation techniques for a genome-wide association study, aiming to identify candidate SNP loci and genes associated with growth traits. A significant concentration of these genes was observed on chromosome 17, which is primarily involved in skeletal muscle and embryonic development and cell proliferation. Notably, our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs, showing potential for genetic selective breeding efforts. These findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting P. leopardus.

New insights into the genetic loci related to egg weight and age at first egg traits in broiler breeder.

Egg weight (EW) and age at first egg (AFE) are economically important traits in breeder chicken production. The genetic basis of these traits, however, is far from understood, especially for broiler breeders. In this study, genetic parameter estimation, genome-wide association analysis, meta-analysis, and selective sweep analysis were carried out to identify genetic loci associated with EW and AFE in 6,842 broiler breeders. The study found that the heritability of EW ranged from 0.42 to 0.44, while the heritability of AFE was estimated at 0.33 in the maternal line. Meta-analysis and selective sweep analysis identified two colocalized regions on GGA4 that significantly influenced EW at 32 wk (EW32W) and at 43 wk (EW43W) with both paternal and maternal lines. The genes AR, YIPF6, and STARD8 were located within the significant region (GGA4: 366.86-575.50 kb), potentially affecting EW through the regulation of follicle development, cell proliferation, and lipid transfer etc. The promising genes LCORL and NCAPG were positioned within the significant region (GGA4:75.35-75.42 Mb), potentially influencing EW through pleiotropic effects on growth and development. Additionally, 3 significant regions were associated with AFE on chromosomes GGA7, GGA19, and GGA27. All of these factors affected the AFE by influencing ovarian development. In our study, the genomic information from both paternal and maternal lines was used to identify genetic regions associated with EW and AFE. Two genomic regions and eight genes were identified as the most likely candidates affecting EW and AFE. These findings contribute to a better understanding of the genetic basis of egg production traits in broiler breeders and provide new insights into future technology development.

Unravelling novel and pleiotropic genes for cannon bone circumference and bone mineral density in Yorkshire pigs.

Leg weakness is a prevalent health condition in pig farms. The augmentation of cannon bone circumference and bone mineral density can effectively improve limb strength in pigs and alleviate leg weakness. This study measured forelimb cannon bone circumference (fCBC) and rear limb cannon bone circumference (rCBC) using an inelastic tapeline and rear limb metatarsal area bone mineral density (raBMD) using a dual-energy X-ray absorptiometry bone density scanner. The samples of Yorkshire castrated boars were genotyped using a 50K single-nucleotide polymorphism (SNP) array. The SNP-chip data were imputed to the level of whole-genome sequencing data (iWGS). This study used iWGS data to perform genome-wide association studies and identified novel significant SNPs associated with fCBC on SSC6, SSC12, and SSC13, rCBC on SSC12 and SSC14, and raBMD on SSC7. Based on the high phenotypic and genetic correlations between CBC and raBMD, multi-trait meta-analysis was performed to identify pleiotropic SNPs. A significant potential pleiotropic quantitative trait locus (QTL) regulating both CBC and raBMD was identified on SSC15. Bayes fine mapping was used to establish the confidence intervals for these novel QTLs with the most refined confidence interval narrowed down to 56 kb (15.11 to 15.17 Mb on SSC12 for fCBC). Furthermore, the confidence interval for the potential pleiotropic QTL on SSC15 in the meta-analysis was narrowed down to 7.45 kb (137.55 to137.56 Mb on SSC15). Based on the biological functions of genes, the following genes were identified as novel regulatory candidates for different phenotypes: DDX42, MYSM1, FTSJ3, and MECOM for fCBC; SMURF2, and STC1 for rCBC; RGMA for raBMD. Additionally, RAMP1, which was determined to be located 23.68 kb upstream of the confidence interval of the QTL on SSC15 in the meta-analysis, was identified as a potential pleiotropic candidate gene regulating both CBC and raBMD. These findings offered valuable insights for identifying pathogenic genes and elucidating the genetic mechanisms underlying CBC and BMD.

Leg weakness, a highly prevalent health condition in pig breeding farms, adversely affects the lifespan of breeding pigs. The augmentation of cannon bone circumference (CBC) and bone mineral density (BMD), which are objective measures of limb strength in pigs, can effectively alleviate leg weakness. To identify candidate genes regulating CBC and BMD in pigs, this study performed single-trait genome-wide association studies and multi-trait meta-analysis on all individuals with phenotype data. Additionally, the confidence intervals of quantitative trait locus (QTL) were determined using Bayesian methods. Four CBC-associated QTLs and one BMD-associated QTL were identified. Additionally, one potential pleiotropic QTL associated with both CBC and rear limb metatarsal area BMD (raBMD) was identified. This study demonstrated that DDX42, MYSM1, FTSJ3, and MECOM were candidate genes regulating forelimb CBC, while SMURF2 and STC1 were candidate genes regulating rear limb CBC. Additionally, RGMA was demonstrated to regulate raBMD, while RAMP1 was identified as a potential pleiotropic gene regulating both CBC and raBMD. The findings of this study provide valuable insights into the genetic mechanisms underlying limb growth and bone mineral accumulation.

Genetic basis of sow hyperprolificacy and litter size optimization based on a genome-wide association study.

Over the last few decades, there has been a constant increase in sow litter size, the consequences of which include parturition duration extension, an increase in the percentage of stillborn and hypoxic piglets, and increased variation in piglet birth weight, which reduces their vitality. As such, it seems clear that further increasing sow fertility will generate difficulties and costs in rearing numerous litters with low birth weights. Therefore, the current study aimed to analyze the genetic background of sow hyperprolifcacy using a genome-wide association study (GWAS). The research included 144 sows in the maternal component, divided into two equal groups. The first group (control) consisted of females giving birth to the optimal number of piglets in their third and fourth litters (14-16), while the second group (cases) included those with excessive litter size (>16). The analyzed sows were genotyped using Illumina's PorcineSNP60v2 BeadChip microarray, comprising 64,232 single nucleotide polymorphisms (SNPs). Statistical analysis using R included quality control of genotyping data and GWAS analysis based on five logistic regression models (dominant, codominant, overdominant, recessive, and log-additive) with a single SNP marker as the explanatory variable. On this basis, one SNP (SIRI0000069) was identified on chromosome seven within the EFCAB11 (EF-hand calcium binding domain 11) gene that had a statistically significant effect on sow hyperprolificacy. Additionally, ten SNPs (INRA0007631, ALGA0011600, ALGA0043433, ALGA0043428, M1GA0010535 ALGA00443338, ALGA0087116, MARC0056787, ALGA0112928, and ALGA0089047) had a relationship with the analyzed feature at a level close to significance, set at 1-5. These SNPs appear important since they are located on chromosomes on which a large number of quantitative trait loci (QTLs) and SNPs associated with reproductive characteristics, including litter size, have been identified.

Genome-wide association and functional annotation analysis for the calving interval in Nellore cattle.

Calving interval (CI) measures the number of days between two consecutive calves of the same cow, and previous studies based on phenotype and pedigree data reported low heritability for this trait. However, the genetic architecture of CI in the Nellore breed was not evaluated based on genomic data. Thus, this study aimed to estimate the heritability based on genomic data and carry out a genome-wide association study (GWAS) for CI in the Nellore breed, using 12,599 pedigree records, 5078 CI records, and 3818 animals genotyped with 50k SNPchip panel. Both quality control and GWAS were performed in BLUPF90 family packages, which use the single-step genomic best linear unbiased predictor (ssGBLUP) method. The average CI was 427.6 days, with a standard deviation of 106.9 and a total range of 270-730 days. The heritability estimate was 0.04 ± 0.04. The p-values of GWAS analysis resulted in a genomic inflation factor (lambda) of 1.08. The only significant SNP (rs136725686) at the genome-wide level (p-value = 1.53E-06) was located on BTA13. Other 19 SNPs were significant at the chromosome-wide level, distributed on BTA1, 2, 3, 6, 10, 13, 14, 17, 18, 22, and 26. Functional annotation analysis found thirty-six protein-coding genes, including genes related to cell cycle (RAD21, BCAR3), oocyte function (LHX8, CLPX, UTP23), immune system (TXK, TEC, NFATC2), endocrine function (LRRFIP2, GPR158), estrous cycle (SLC38A7), and female fertility (CCK, LYZL4, TRAK1, FOXP1, STAC). Therefore, CI is a complex trait with small heritability in Nellore cattle, and various biological processes may be involved with the genetic architecture of CI in Nellore cattle.