Genome-wide DNA methylation analysis using next-generation sequencing to reveal candidate genes responsible for boar taint in pigs.

Boar taint (BT) is an offensive flavor observed in non-castrated male pigs that reduces the carcass price. Surgical castration effectively avoids the taint but is associated with animal welfare concerns. The functional annotation of farm animal genomes for understanding the biology of complex traits can be used in the selection of breeding animals to achieve favorable phenotypic outcomes. The characterization of pig epigenomes/methylation changes between animals with high and low BT and genome-wide epigenetic markers that can predict BT are lacking. Reduced representation bisulfite sequencing of DNA methylation patterns based on next-generation sequencing is an efficient technology to identify candidate epigenetic biomarkers associated with BT. Three different BT levels were analyzed using reduced representation bisulfite sequencing data to calculate the methylation levels of cytosine and guanine dinucleotide (CpG) sites. The co-analysis of differentially methylated CpG sites identified by this study and differentially expressed genes identified by a previous study found 32 significant co-located genes. The joint analysis of GO terms and pathways revealed that methylation and gene expression of seven candidate genes were associated with BT; in particular, FASN plays a key role in fatty acid biosynthesis, and PEMT might be involved in estrogen regulation and the development of BT. This study is the first to report the genome-wide DNA methylation profiles of BT in pigs using next-generation sequencing and summarize candidate genes associated with epigenetic markers of BT, which could contribute to the understanding of the functional biology of BT traits and selective breeding of pigs against BT based on epigenetic biomarkers.

Gene co-expression networks from RNA sequencing of dairy cattle identifies genes and pathways affecting feed efficiency.

BACKGROUND: Selection for feed efficiency is crucial for overall profitability and sustainability in dairy cattle production. Key regulator genes and genetic markers derived from co-expression networks underlying feed efficiency could be included in the genomic selection of the best cows. The present study identified co-expression networks associated with high and low feed efficiency and their regulator genes in Danish Holstein and Jersey cows. RNA-sequencing data from Holstein and Jersey cows with high and low residual feed intake (RFI) and treated with two diets (low and high concentrate) were used. Approximately 26 million and 25 million pair reads were mapped to bovine reference genome for Jersey and Holstein breed, respectively. Subsequently, the gene count expressions data were analysed using a Weighted Gene Co-expression Network Analysis (WGCNA) approach. Functional enrichment analysis from Ingenuity® Pathway Analysis (IPA®), ClueGO application and STRING of these modules was performed to identify relevant biological pathways and regulatory genes. RESULTS: WGCNA identified two groups of co-expressed genes (modules) significantly associated with RFI and one module significantly associated with diet. In Holstein cows, the salmon module with module trait relationship (MTR) = 0.7 and the top upstream regulators ATP7B were involved in cholesterol biosynthesis, steroid biosynthesis, lipid biosynthesis and fatty acid metabolism. The magenta module has been significantly associated (MTR = 0.51) with the treatment diet involved in the triglyceride homeostasis. In Jersey cows, the lightsteelblue1 (MTR = - 0.57) module controlled by IFNG and IL10RA was involved in the positive regulation of interferon-gamma production, lymphocyte differentiation, natural killer cell-mediated cytotoxicity and primary immunodeficiency. CONCLUSION: The present study provides new information on the biological functions in liver that are potentially involved in controlling feed efficiency. The hub genes and upstream regulators (ATP7b, IFNG and IL10RA) involved in these functions are potential candidate genes for the development of new biomarkers. However, the hub genes, upstream regulators and pathways involved in the co-expressed networks were different in both breeds. Hence, additional studies are required to investigate and confirm these findings prior to their use as candidate genes.

Transcriptomics-genomics data integration and expression quantitative trait loci analyses in oocyte donors and embryo recipients for improving invitro production of dairy cattle embryos.

In this paper we first provide a brief review of main results from our previously published studies on genome-wide gene expression (transcriptomics) in donor and recipient cattle used in invitro production (IVP) of embryos and embryo transfer (ET). Then, we present novel results from applying integrative systems genomics and biological analyses where transcriptomics data are combined with genomic data in both donor and recipient cattle to map expression quantitative trait loci (eQTLs). The eQTLs are genetic markers that can regulate or control the expression of genes in the entire genome, via complex molecular mechanisms, and thus can act as a powerful tool for genomic and gene-assisted selection. We identified significant eQTLs potentially controlling the expression of 13 candidate genes for donor cow quality (IVP parameters; e.g. cyclin B1 (CCNB1), outer dense fiber of sperm tails 2 like (ODF2L)) and 19 candidate genes for recipient cows quality (endometrial receptivity; e.g. ER membrane protein complex subunit 9 (EMC9), mannosidase beta (MANBA), peptidase inhibitor 16 (PI16)). Annotation and colocation of detected eQTLs show that some of the eQTLs are in the same genomic regions previously reported as QTLs for reproduction-related traits. However, eQTLs and the candidate genes identified should be further validated in larger populations before implementation as genetic markers or used in genomic selection for improving IVP and ET performance.

Systems genetics analysis of pharmacogenomics variation during antidepressant treatment.

Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel the involved genetic components. Moreover, we investigated the potential difference in the genetic interaction networks underlying SSRI treatment response over time. We found four hub genes (ASCC3, PPARGC1B, SCHIP1 and TMTC2) with different connectivity in the initial SSRI treatment period (baseline to week 4) compared with the subsequent period (4-8 weeks after initiation), suggesting that different genetic networks are important at different times during SSRI treatment. The strongest interactions in the initial SSRI treatment period involved genes encoding transcriptional factors, and in the subsequent period genes involved in calcium homeostasis. In conclusion, we suggest a difference in genetic interaction networks between initial and subsequent SSRI response.

RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle.

BACKGROUND: The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. RESULTS: The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences < ~200 bases) were sequenced, 52 million reads were mapped, and 24,616 known transcripts were quantified according to the bovine reference genome. A comparison of the high- and low-RFI groups revealed 70 and 19 significantly DEGs in Holstein and Jersey cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. CONCLUSION: We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP's and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins.

Genomic study and Medical Subject Headings enrichment analysis of early pregnancy rate and antral follicle numbers in Nelore heifers.

Zebu animals () are known to take longer to reach puberty compared with taurine animals (), limiting the supply of animals for harvest or breeding and impacting profitability. Genomic information can be a helpful tool to better understand complex traits and improve genetic gains. In this study, we performed a genomewide association study (GWAS) to identify genetic variants associated with reproductive traits in Nelore beef cattle. Heifer pregnancy (HP) was recorded for 1,267 genotyped animals distributed in 12 contemporary groups (CG) with an average pregnancy rate of 0.35 (±0.01). Disregarding one of these CG, the number of antral follicles (NF) was also collected for 937 of these animals, with an average of 11.53 (±4.43). The animals were organized in CG: 12 and 11 for HP and NF, respectively. Genes in linkage disequilibrium (LD) with the associated variants can be considered in a functional enrichment analysis to identify biological mechanisms involved in fertility. Medical Subject Headings (MeSH) were detected using the MESHR package, allowing the extraction of broad meanings from the gene lists provided by the GWAS. The estimated heritability for HP was 0.28 ± 0.07 and for NF was 0.49 ± 0.09, with the genomic correlation being -0.21 ± 0.29. The average LD between adjacent markers was 0.23 ± 0.01, and GWAS identified genomic windows that accounted for >1% of total genetic variance on chromosomes 5, 14, and 18 for HP and on chromosomes 2, 8, 11, 14, 15, 16, and 22 for NF. The MeSH enrichment analyses revealed significant ( < 0.05) terms associated with HP-"Munc18 Proteins," "Fucose," and "Hemoglobins"-and with NF-"Cathepsin B," "Receptors, Neuropeptide," and "Palmitic Acid." This is the first study in Nelore cattle introducing the concept of MeSH analysis. The genomic analyses contributed to a better understanding of the genetic control of the reproductive traits HP and NF and provide new selection strategies to improve beef production.

Systems genetics and genome-wide association approaches for analysis of feed intake, feed efficiency, and performance in beef cattle.

Feed intake, feed efficiency, and weight gain are important economic traits of beef cattle in feedlots. In the present study, we investigated the physiological processes underlying such traits from the point of view of systems genetics. Firstly, using data from 1334 Nellore (Bos indicus) cattle and 943,577 single nucleotide polymorphisms (SNPs), a genome-wide association analysis was performed for dry matter intake, average daily weight gain, feed conversion ratio, and residual feed intake with a Bayesian Lasso procedure. Genes within 50-kb SNPs, most relevant for explaining the genomic variance, were annotated and the biological processes underlying the traits were inferred from Database for Annotation, Visualization and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results indicated several putative genomic regions associated with the target phenotypes and showed that almost all genomic variances were in the SNPs located in the intergenic and intronic regions. We further identified five main metabolic pathways related to ion transport, body composition, and feed intake control, which influenced the four phenotypes simultaneously. The systems genetics approach used in this study revealed novel pathways related to feed efficiency traits in beef cattle.

SNP annotation-based whole genomic prediction and selection: an application to feed efficiency and its component traits in pigs.

The study investigated genetic architecture and predictive ability using genomic annotation of residual feed intake (RFI) and its component traits (daily feed intake [DFI], ADG, and back fat [BF]). A total of 1,272 Duroc pigs had both genotypic and phenotypic records, and the records were split into a training (968 pigs) and a validation dataset (304 pigs) by assigning records as before and after January 1, 2012, respectively. SNP were annotated by 14 different classes using Ensembl variant effect prediction. Predictive accuracy and prediction bias were calculated using Bayesian Power LASSO, Bayesian A, B, and Cπ, and genomic BLUP (GBLUP) methods. Predictive accuracy ranged from 0.508 to 0.531, 0.506 to 0.532, 0.276 to 0.357, and 0.308 to 0.362 for DFI, RFI, ADG, and BF, respectively. BayesCπ100.1 increased accuracy slightly compared to the GBLUP model and other methods. The contribution per SNP to total genomic variance was similar among annotated classes across different traits. Predictive performance of SNP classes did not significantly differ from randomized SNP groups. Genomic prediction has accuracy comparable to observed phenotype, and use of genomic prediction can be cost effective by replacing feed intake measurement. Genomic annotation had less impact on predictive accuracy traits considered here but may be different for other traits. It is the first study to provide useful insights into biological classes of SNP driving the whole genomic prediction for complex traits in pigs.

Additive and epistatic genome-wide association for growth and ultrasound scan measures of carcass-related traits in Brahman cattle.

Genome-wide association studies are routinely used to identify genomic regions associated with traits of interest. However, this ignores an important class of genomic associations, that of epistatic interactions. A genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) using highly dense markers can detect epistatic interactions, but is a difficult task due to multiple testing and computational demand. However, It is important for revealing complex trait heredity. This study considers analytical methods that detect statistical interactions between pairs of loci. We investigated a three-stage modelling procedure: (i) a model without the SNP to estimate the variance components; (ii) a model with the SNP using variance component estimates from (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for genome-wide epistasis analysis. We fitted these three-stage models to field data for growth and ultrasound measures for subcutaneous fat thickness in Brahman cattle. The study demonstrated the usefulness of modelling epistasis in the analysis of complex traits as it revealed extra sources of genetic variation and identified potential candidate genes affecting the concentration of insulin-like growth factor-1 and ultrasound scan measure of fat depth traits. Information about epistasis can add to our understanding of the complex genetic networks that form the fundamental basis of biological systems.

Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep.

AIM: To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history. METHODS: In a 3 × 2 factorial design, twin-pregnant ewes were for the last 6 weeks of gestation (term = 147 days) assigned to HIGH (N = 13; 150 and 110% of energy and protein requirements, respectively), NORM (N = 9; 100% of requirements) or LOW (N = 14; 50% of requirements) diets. The twin offspring were raised on high-carbohydrate-high-fat (HCHF; N = 35) or conventional (CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose (GTT; overnight fasted), insulin (ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity. RESULTS: Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than glucose, and HIGH lambs became more hyperglycaemic, hyperlactataemic and secreted less insulin compared to the hypercholesterolaemic LOW lambs. Propionate-induced insulin secretion was virtually abolished in fasted HCHF lambs, but upregulated in fasted compared to fed CONV lambs. HCHF lambs had the greatest glucose-induced insulin secretory responses. CONCLUSION: Prenatal malnutrition differentially programmed glucose-lactate metabolic pathways and cholesterol homeostasis. Prenatal overnutrition predisposed for hyperglycaemia and hyperlactataemia, whereas undernutrition predisposed for hypercholesterolaemia upon exposure to an obesogenic diet. Prenatal overnutrition (not undernutrition) interfered with pancreatic insulin secretion by non-glucose-dependent mechanisms.

Molecular genetic diversity and genetic structure of Vietnamese indigenous pig populations.

The study characterized genetic diversity and genetic structure of five indigenous pig populations (Ha Lang, Muong Te, Mong Cai, Lung and Lung Pu), two wild pig populations (Vietnamese and Thai wild pigs) and an exotic pig breed (Yorkshire) using FAO/ISAG recommended 16 microsatellite markers in 236 samples. All estimated loci were very polymorphic indicated by high values of polymorphism information content (from 0.76 in S0225 to 0.92 in Sw2410). Indigenous populations had very high level of genetic diversity (mean He = 0.75); of all indigenous breeds, Lung Pu showed highest mean number of alleles (MNA = 10.1), gene diversity (He = 0.82), allele richness (5.33) and number of private alleles (10). Thirteen percentage of the total genetic variation observed was due to differences among populations. The neighbour-joining dendrogram obtained from Nei's standard genetic distance differentiated eight populations into four groups including Yorkshire, two wild populations, Mong Cai population and a group of four other indigenous populations. The Bayesian clustering with the admixture model implemented in Structure 2.1 indicated seven possible homogenous clusters among eight populations. From 79% (Ha Lang) to 98% (Mong Cai). individuals in indigenous pigs were assigned to their own populations. The results confirmed high level of genetic diversity and shed a new light on genetic structure of Vietnam indigenous pig populations.

Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds.

Obesity has reached epidemic proportions globally and has become the cause of several major health risks worldwide. Presently, more than 100 loci have been related to obesity and metabolic traits in humans by genome-wide association studies. The complex genetic architecture behind obesity has triggered a need for the development of better animal models than rodents. The pig has emerged as a very promising biomedical model to study human obesity traits. In this study, we have characterized the expression patterns of six obesity-related genes, leptin (LEP), leptin receptor (LEPR), melanocortin 4 receptor (MC4R), fat mass and obesity associated (FTO), neuronal growth regulator 1 (NEGR)1 and adiponectin (ADIPOQ), in seven obesity-relevant tissues (liver; muscle; pancreas; hypothalamus; and retroperitoneal, subcutaneous and mesenteric adipose tissues) in two pig breeds (production pigs and Göttingen minipigs) that deviate phenotypically and genetically from each other with respect to obesity traits. We observe significant differential expression for LEP, LEPR and ADIPOQ in muscle and in all three adipose tissues. Interestingly, in pancreas, LEP expression is only detected in the fat minipigs. FTO shows significant differential expression in all tissues analyzed, and NEGR1 shows significant differential expression in muscle, pancreas, hypothalamus and subcutaneous adipose tissue. The MC4R transcript can be detected only in hypothalamus. In general, the expression profiles of the investigated genes are in accordance with those observed in human studies. Our study shows that both the differences between the investigated breeds and the phenotypic state with respect to obesity/leanness play a large role for differential expression of the obesity-related genes.

Genetic parameters for male fertility and its relationship to skatole and androstenone in Danish Landrace boars.

Concerns have been raised regarding selection against the boar taint compounds, androstenone and skatole, due to potential unfavorable genetic correlations with important male fertility traits (i.e., selection of boars with low levels of these boar taint compounds might also reduce male fertility). Hence, the objective of this investigation was to study the genetic association between direct measures of male fertility and the boar taint compounds in Danish Landrace pigs. Concentrations of skatole and androstenone in the back fat were available for approximately 6,000 and 1,000 Landrace boars, respectively. The litter size traits, such as total number born, live piglets at d 5, and piglet survival until d 5 on relatives of the slaughter boars, were extracted from the Danish Landrace breeding program, yielding 35,715 records. Semen volume, sperm concentration, subjective sperm quality score, and total number of sperm were available from 95,267 ejaculates. These ejaculates were collected between 2005 and 2012 and originated from 3,145 Landrace boars from 12 AI stations in Denmark. The traits were analyzed using single and multitrait animal models including univariate random regression models. Skatole and androstenone concentrations were moderate to highly heritable (i.e., 0.33 and 0.59, respectively). The genetic correlation between the two compounds was moderate (0.40). Genetic variance of sperm production per ejaculate increased during the productive life of the boar, resulting in heritability estimates increasing from 0.18 to 0.31. Genetic correlations between sperm production per ejaculate at different ages were high and generally larger than 0.8, indicating that later genetic merit can be predicted from records at an early age. The heritability (based on service-sire genetic component) of both total number of piglets born and survival to d 5 were 0.02, and the correlation between these effects and the additive genetic effect on boar taint ranged from 0.05 to -0.40 (none of these correlations were significantly different from zero). Most importantly, the genetic correlations between skatole and androstenone and the different semen traits tended to be more favorable with increase in age of the boars. In conclusion, these data suggest that concentrations of skatole and androstenone can be reduced through genetic selection without negatively affecting important male fertility traits in Danish Landrace pigs.

Genetic parameters for different measures of feed efficiency and related traits in boars of three pig breeds.

Residual feed intake (RFI) is commonly used as a measure of feed efficiency at a given level of production. A total of 16,872 pigs with their pedigree traced back as far as possible was used to estimate genetic parameters for RFI, growth performance, food conversion ratio (FCR), body conformation, and feeding behavior traits in 3 Danish breeds [Duroc (DD), Landrace (LL), and Yorkshire (YY)]. Two measures of RFI were considered: residual feed intake 1 (RFI1) was calculated based on regression of daily feed intake (DFI) from 30 to 100 kg on initial test weight and ADG from 30 to 100 kg (ADG2). Residual feed intake 2 (RFI2) was as RFI1, except it was also regressed with respect to backfat (BF). The estimated heritabilities for RFI1 and RFI2 were 0.34 and 0.38 in DD, 0.34 and 0.36 in LL, and 0.39 and 0.40 in YY, respectively. The heritabilities ranged from 0.32 (DD) to 0.54 (LL) for ADG2, from 0.54 (DD) to 0.67 (LL) for BF, and from 0.13 (DD) to 0.19 (YY) for body conformation. Feeding behavior traits including DFI, number of visits to feeder per day (NVD), total time spent eating per day (TPD), feed intake rate (FR), feed intake per visit (FPV), and time spent eating per visit (TPV) were moderately to highly heritable. Residual feed intake 2 was genetically independent of ADG2 and BF in all breeds, except it had low genetic correlation to ADG2 in YY (0.2). Residual feed intake 1 was also genetically independent of ADG2 in DD and LL. Both RFI traits had strong genetic correlations with DFI (0.85 to 0.96) and FCR (0.76 to 0.99). They had low or no genetic correlations with feeding behavior traits. Unfavorable genetic correlations were found between ADG2 and both BF and DFI. Among feeding behavior traits, DFI had low genetic correlations to other traits in all breeds. High and negative genetic correlations were also found between TPD with FR (-0.79 in YY to -0.88 in DD), NVD, and TPD (-0.91 in DD to -0.94 in YY) and between NVD and FPV (-0.83 in DD to -0.91 in YY) in all breeds. The genetic trend for feed efficiency was favorable in all breeds regardless of the definition of feed efficiency used. In summary, RFI1 and RFI2 were heritable and selection for reduced RFI2 can be performed without adversely affecting ADG and BF and could replace FCR in the selection index for the Danish pig breeds. Selection could also be based on RFI1 for breeds with fewer concerns about a negative effect of BF or for breeds that do not have BF records.

Genetic parameters for androstenone and skatole as indicators of boar taint and their relationship to production and litter size traits in Danish Landrace.

Boar taint is an offensive odor that affects the smell and taste of cooked pork, resulting mainly from the accumulation of skatole and androstenone in the back fat of intact males. The aim of the study was to estimate genetic parameters for skatole and androstenone and their genetic relationship to production and litter size traits. Concentrations of skatole and androstenone in the back fat were available for approximately 6,000 and 1,000 Landrace boars, respectively. The concentrations were log-transformed to align phenotypic measures to a normal distribution. Heritability estimates for Log(skatole) and Log(androstenone) were 0.33 and 0.59, respectively. The genetic correlation between the 2 measures of boar taint was 0.37, suggesting that genetic selection against boar taint based on only 1 of the chemical compounds could be insufficient. The boar taint compounds had low and mostly favorable genetic correlations with the production traits. Most noticeable, a favorable genetic correlation of -0.20 between meat percentage and Log(skatole) was estimated and hence continued selection for lean pigs can also slowly reduce the level of boar taint if the desired carcass weight is kept constant. The relationship between litter size traits (measured on sows related to boars) and boar taint compounds was low and not significantly different from 0. In conclusion, skatole and androstenone can be reduced through selection without affecting important economical production and litter size traits. Therefore, animal breeding offers an effective and sustainable solution to surgical castration of male piglets.

Polymorphisms of the SLC11A1 gene and resistance to bovine tuberculosis in African Zebu cattle.

Bovine tuberculosis (BTB) is a considerable health threat to livestock keepers and general communities in many developing countries. Information on genetic resistance or susceptibility because of polymorphisms of candidate genes could be used in making selection decisions for breeding disease tolerant/resistant animals. Here, we investigated associations between polymorphisms at the solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1 gene (SLC11A1, previously known as natural resistant associated macrophage protein 1, NRAMP1), with BTB phenotypes in Chadian cattle. Phenotypes were (i) single intradermal comparative cervical tuberculin test (SICCT) outcome, (ii) presence of gross visible lung lesions, (iii) a bacteriological culture test outcome and (iv) a predicted true BTB infection status using a Bayesian model. All traits were recorded as binary (presence or absence) traits. A total of 211 cattle were genotyped for a microsatellite within the SLC11A1 candidate gene. Standard linear and threshold-liability models regressing BTB traits on copy number of SLC11A1 alleles revealed statistically significant effects of SLC11A1 alleles (P < 0.001) on most BTB traits. Polymorphisms (alleles 211, 215 and 217) are significantly related to lower incidence of BTB traits in Chadian cattle. This is the first study to report the association of SLC11A1 gene polymorphisms with BTB traits in Chadian or any other African cattle breeds.

Genetical systems biology in livestock: application to gonadotrophin releasing hormone and reproduction.

Genetical systems biology or systems genetics treats the genome as the central reference point for all omics variations and is an emerging new branch of systems biology. Quantitative genetic principles were developed for high-throughput genomic, transcriptomic and metabolomic data observed in large populations. New statistical genetic models were developed for expression quantitative trait loci (eQTL), namely, marker regression eQTL mapping and marker-expression co-factor mapping. Evaluations of power to detect eQTL showed that sample size requirements are higher for detecting trans-acting genes than cis-acting genes. Power is higher for eQTL with high heritability than for eQTL with low heritability. These results will be valuable for systems genetic investigations. Gonadotrophin releasing hormone (GnRH) and its receptor gene (GnRH-R) are crucial for mammalian reproduction. Whole genome scan of eQTLs for GnRH-R gene expression in mouse showed three possible trans-eQTL regions on chr 13 and 19, harbouring regulatory genes. Applications of genetical genomics in systems biology were identified as: (1) detection and validation of causal gene for complex traits; (2) development of genetic interaction networks; (3) prediction of transcription factor binding sites and (4) in data-driven systems biology. These applications were illustrated using data on eQTL, protein network and signalling pathways for GnRH. Gpr54 (G protein-coupled receptor kinase 54), Prl (prolactin), Ins1 (insulin) and Fos (viral oncogenes) were found to be major regulators of GnRH and GnRH-R; thus validating their important role in reproduction, mammary gland development and sexual (im)maturity. These results will be useful for further study of mammalian reproductive biology.

Selection on multiple QTL with control of gene diversity and inbreeding for long-term benefit.

The purpose of this study was to develop and investigate selection strategies that aim at maximizing long-term genetic response while conserving gene diversity and controlling inbreeding in populations of limited effective size, assuming complete knowledge of all genes affecting a quantitative trait. Three selection strategies were proposed to select on 100 quantitative trait loci (QTL) and compared with truncation selection on breeding value. Alternative selection strategies aimed at maximizing the average breeding value of parents with a penalty on (1) the number of unfavourable QTL genotypes among parents (OS-I), (2) the negative of the logarithm of the frequency of the favourable allele at each QTL among parents (OS-II), and (3) the average pedigree relationship among parents (OS-III). When all QTL and their effects were known, the strategies examined were able to obtain extra long-term responses, conserve QTL diversity and reduce inbreeding, compared with truncation selection. Strategy OS-II was the most effective in conserving QTL diversity and OS-III in reducing inbreeding. By changing the magnitude of the penalties applied, the impact on long-term response, inbreeding and diversity can be controlled. Extra long-term responses over truncation selection of OS-I and OS-II were even greater when effects of QTL were estimated rather than assumed known, indicating the applicability of results to practical strategies for marker-assisted selection. Extra responses are expected to be reduced for larger population sizes.

Genetic correlations between body condition scores and fertility in dairy cattle using bivariate random regression models.

Genetic correlations between body condition score (BCS) and fertility traits in dairy cattle were estimated using bivariate random regression models. BCS was recorded by the Swiss Holstein Association on 22,075 lactating heifers (primiparous cows) from 856 sires. Fertility data during first lactation were extracted for 40,736 cows. The fertility traits were days to first service (DFS), days between first and last insemination (DFLI), calving interval (CI), number of services per conception (NSPC) and conception rate to first insemination (CRFI). A bivariate model was used to estimate genetic correlations between BCS as a longitudinal trait by random regression components, and daughter's fertility at the sire level as a single lactation measurement. Heritability of BCS was 0.17, and heritabilities for fertility traits were low (0.01-0.08). Genetic correlations between BCS and fertility over the lactation varied from: -0.45 to -0.14 for DFS; -0.75 to 0.03 for DFLI; from -0.59 to -0.02 for CI; from -0.47 to 0.33 for NSPC and from 0.08 to 0.82 for CRFI. These results show (genetic) interactions between fat reserves and reproduction along the lactation trajectory of modern dairy cows, which can be useful in genetic selection as well as in management. Maximum genetic gain in fertility from indirect selection on BCS should be based on measurements taken in mid lactation when the genetic variance for BCS is largest, and the genetic correlations between BCS and fertility is strongest.

Genetic and phenotypic parameters for conformation and yield traits in three Swiss dairy cattle breeds.

This study presents genetic parameters for conformation traits and their genetic and phenotypic correlations with milk production traits and somatic cell score (SCS) in three Swiss dairy cattle breeds. Data on first lactations from Holstein (67,839), Brown Swiss (173,372) and Red & White breeds (53,784) were available. Analysed conformation traits were stature and heart girth (both in cm), and linear scores of body depth, rump width, dairy character or muscularity, and body condition score (only in Holstein). A sire model, with relationships among sires, was used for all breeds and traits and variance components were estimated using AS-REML. Heritabilities for stature were high (0.6-0.8), and for the linear type traits ranged from 0.3 to 0.5, for all breeds. Genetic correlations with production traits (milk, fat and protein yield) and SCS differed between the dairy breeds. Most markedly, stronger correlations were found between SCS and some conformation traits in Brown Swiss and Red & White, indicating that a focus on a larger and more 'dairy' type in these breeds would lead to increased SCS. Another marked difference was that rump width correlated positively with milk yield traits in Holstein and Red & White, but negative in Brown Swiss. Results indicate that conformation traits generally can be used as predictors for various purposes in dairy cattle breeding, but may require specific adaptation for each breed.