Genome-wide association studies for feedlot and growth traits in cattle

A genome wide-association study for production traits in cattle was carried out using genotype data from the 10K Affymetrix (Santa Clara, CA) and the 50K Illumina (San Diego, CA) SNP chips. The results for residual feed intake (RFI), BW, and hip height in 3 beef breed types (Bos indicus, Bos taurus, and B. indicus × B. taurus), and for stature in dairy cattle, are presented. The aims were to discover SNP associated with all traits studied, but especially RFI, and further to test the consistency of SNP effects across different cattle populations and breed types. The data were analyzed within data sets and within breed types by using a mixed model and fitting 1 SNP at a time. In each case, the number of significant SNP was more than expected by chance alone. A total of 75 SNP from the reference population with 50K chip data were significant (P < 0.001) for RFI, with a false discovery rate of 68%. These 75 SNP were mapped on 24 different BTA. Of the 75 SNP, the 9 most significant SNP were detected on BTA 3, 5, 7, and 8, with P ≤ 6.0 × 10(-5). In a population of Angus cattle divergently selected for high and low RFI and 10K chip data, 111 SNP were significantly (P < 0.001) associated with RFI, with a false discovery rate of 7%. Approximately 103 of these SNP were therefore likely to represent true positives. Because of the small number of SNP common to both the 10K and 50K SNP chips, only 27 SNP were significantly (P < 0.05) associated with RFI in the 2 populations. However, other chromosome regions were found that contained SNP significantly associated with RFI in both data sets, although no SNP within the region showed a consistent effect on RFI. The SNP effects were consistent between data sets only when estimated within the same breed type.     

Genome-wide association studies of female reproduction in tropically adapted beef cattle

The genetics of reproduction is poorly understood because the heritabilities of traits currently recorded are low. To elucidate the genetics underlying reproduction in beef cattle, we performed a genome-wide association study using the bovine SNP50 chip in 2 tropically adapted beef cattle breeds, Brahman and Tropical Composite. Here we present the results for 3 female reproduction traits: 1) age at puberty, defined as age in days at first observed corpus luteum (CL) after frequent ovarian ultrasound scans (AGECL); 2) the postpartum anestrous interval, measured as the number of days from calving to first ovulation postpartum (first rebreeding interval, PPAI); and 3) the occurrence of the first postpartum ovulation before weaning in the first rebreeding period (PW), defined from PPAI. In addition, correlated traits such as BW, height, serum IGF1 concentration, condition score, and fatness were also examined. In the Brahman and Tropical Composite cattle, 169 [false positive rate (FPR) = 0.262] and 84 (FPR = 0.581) SNP, respectively, were significant (P < 0.001) for AGECL. In Brahman, 41% of these significant markers mapped to a single chromosomal region on BTA14. In Tropical Composites, 16% of these significant markers were located on BTA5. For PPAI, 66 (FPR = 0.67) and 113 (FPR = 0.432) SNP were significant (P < 0.001) in Brahman and Tropical Composite, respectively, whereas for PW, 68 (FPR = 0.64) and 113 (FPR = 0.432) SNP were significant (P < 0.01). In Tropical Composites, the largest concentration of PPAI markers were located on BTA5 [19% (PPAI) and 23% (PW)], and BTA16 [17% (PPAI) and 18% (PW)]. In Brahman cattle, the largest concentration of markers for postpartum anestrus was located on BTA3 (14% for PPAI and PW) and BTA14 (17% PPAI). Very few of the significant markers for female reproduction traits for the Brahman and Tropical Composite breeds were located in the same chromosomal regions. However, fatness and BW traits as well as serum IGF1 concentration were found to be associated with similar genome regions within and between breeds. Clusters of SNP associated with multiple traits were located on BTA14 in Brahman and BTA5 in Tropical Composites.     

A retrospective clinical study of osteochondrosis dissecans in 21 horses

Osteochondrosis dissecans was diagnosed clinically and radiographically in 31 joints of 21 horses. The horses ranged in age from 8 months to 5 years at the time of presentation. The usual age of onset of clinical signs was 18 to 24 months. Presenting complaints included joint effusion and lameness of either gradual or sudden onset. In Thoroughbred horses, the stifle joint was the most common site of lesions and in Standardbred horses lesions occurred more commonly in the hock. In 16 of the 21 horses, the contralateral joint was radiographed and 9 of these horses had bilateral lesions. Thoroughbred horses were affected most commonly, followed by Standardbred horses. The prevalence was higher in males than females, the male: female ratio being 2.5:1.     

Incidence of osteochondrosis (dissecans) in Dutch warmblood horses presented for pre-purchase examination

Data are lacking in the literature regarding the incidence of osteochondrosis (dissecans) [OC(D)] in relation to lameness evaluation in Dutch Warmblood horses. The objective of this retrospective study was to assess the incidence of radiological abnormalities consistent with osteochondrosis or osteochondrosis dissecans in 1,231 sound Dutch Warmblood (DW) horses presented for pre-purchase examination. Standardised (Dutch) pre-purchase examination protocols were evaluated. The pre-purchase examination included a clinical, lameness and radiological evaluation, performed at a private equine clinic in the Netherlands. Radiographical examination included views of the distal (DIP) and proximal (PIP) interphalangeal, metacarpo- and metatarsophalangeal (MCP/MTP), tarsocrural (TC) and femoropatellar (FP) joints. Radiographical evidence of OC(D) was found in 44.3% of clinically sound DW horses. In this study, 443 horses (36%, n = 1,231) had evidence of OCD and 102 horses (8.3%, n = 1,231) had evidence of OC on pre-purchase radiographs. The results also indicated that the TC joints were significantly more likely to be affected. A considerable number of horses did not demonstrate any lameness, although radiographs revealed OC(D).     

Frequency and severity of osteochondrosis in horses with cervical stenotic myelopathy

We compared the frequency and severity of osteochondrosis lesions in young Thoroughbred horses with cervical stenotic myelopathy (CSM) vs that in clinically normal Thoroughbreds of the same age. All lesions of the cervical vertebrae and appendicular skeleton were classified histologically as osteochondrosis or nonosteochondrosis and were measured for severity. Minimal sagittal diameter was significantly smaller in horses with CSM from C2 through C6; no difference was detected at C7. Severity of cervical vertebral osteochondrosis was greater in the horses with CSM, however frequency was not different. Frequency and severity of nonosteochondrosis lesions were not different in cervical vertebrae or appendicular skeleton. Frequency and severity of appendicular skeleton osteochondrosis lesions were both greater in horses with CSM. Osteochondrosis and nonosteochondrosis lesions were more severe on facets at sites of compression than on facets at noncompressed sites in horses with CSM. However, compression was also observed at sites with no articular facet lesions. The association of widespread osteochondrosis and spinal canal narrowing with CSM suggests CSM may represent a systemic failure in the development or maturation of cartilage and bone.     

Quantitative analysis of short‐ and long‐distance racing performance in young and adult horses and association analysis with functional candidate genes in Spanish Trotter horses

The association of five candidate genes with sporting performance in young and adult Spanish Trotter horses (STHs) was performed according to a previous selection based on quantitative analysis of the trait time per kilometre (TPK). A total of 334 516 records of TPK from 5958 STHs were used to estimate the estimated breeding values (EBVs) at different age groups (young and adults horses) throughout the range of distances (1600–2700 m) using a bicharacter random regression model. The heritability estimated by distance ranged from 0.16 to 0.40, with a different range for the two age groups. Considering the animals with the best and the worst deregressed EBV, 321 STHs were selected for SNP genotyping in MSTN, COX4I2, PDK4, DMRT3 and CKM genes. An association analysis based on ridge and logistic regression revealed that the young trotters with genotype GG in PDK4 (p < 0.05) and AA of DMRT3 (p < 0.001) SNPs show the best potential in short‐distance races, while those carrying the genotype AA in DMRT3 (p < 0.001) and CC in CKM (p < 0.05) genes seem to be the best in long‐distance races. Adult trotters with genotype AA in DMRT3 also display greater speed (p < 0.05) and endurance (p < 0.001).     

Radiological investigations of osteochondrosis dissecans in Standardbred Trotters and Swedish Warmblood horses

A total of 106 Standardbred Trotters and 27 Swedish Warmblood horses, with a radiological diagnosis of osteochondrosis dissecans, were studied over a six year period. The majority were young horses. No statistical difference in frequency between the sexes was demonstrated. In both breeds osteochondrosis was most common in the hock joints, the site of predilection being the distal dorsal tip of the intermediate tibial ridge. On radiographs the lesions of the hock joints were graded on a scale from 0 to 5 according to size, number and localisation of defects and visible loose bodies. The sizes of the loose bodies estimated radiologically were fairly closely correlated with those found at surgery or autopsy.     

Prevalence of osteochondrosis in the limb joints of South German Coldblood horses

This study aimed to quantify the factors associated with the prevalence of the radiological signs of osteochondrosis (OC) and osteochondrosis dissecans (OCD) in South German Coldblood (SGC) horses. The prevalence of OC and OCD in fetlock and hock joints was analysed in 167 young coldblood horses with a mean age of 14 months. The presence of at least one osteochondrotic lesion (OC) in fetlock or hock joints was documented for 61.7% of the horses and 26.9% of the horses had osseus fragments. Osteochondrotic findings at the dorsal aspect of the sagittal ridge of the third metacarpal/metatarsal bone were seen in 53.9% of the horses and palmar/plantar osseous fragments in fetlock joints in 16.2% of the horses. Hock joint OC was found in 40.1% of the horses and hock OCD in 0.6%. Osteochondrotic findings in the distal part of the tibia were prevalent in 28.1% and in the lateral trochlea tali in 17.4% of the horses. The sex of the investigated horses significantly influenced the prevalence of OC in fetlock and hock joints, as well as the findings in the distal part of the tibia and lateral trochlea tali. Age at radiological examination was significant for the prevalence of OC in hock joints, palmar/plantar osseous fragments in fetlock joints and osteochondrotic findings in the distal part of the tibia. Female horses showed a 2-fold higher risk for OC in fetlock and hock joints than male horses. The distribution of the affected horses by age classes showed that radiographic signs of OC in fetlock and hock joints significantly increased at an age of about 1 year. We can conclude from our study that fetlock and hock OC is a prevalent radiographic finding in more than 1-year-old female and male SGC horses.     

Genetic parameters for the prevalence of osteochondrosis in the limb joints of South German Coldblood horses

Heritabilities were estimated for osteochondrosis (OC) in fetlock and hock joints and palmar/plantar osseous fragments in fetlock joints of South German Coldblood (SGC) horses using Residual Maximum Likelihood (REML) under a linear animal model. The analyses were based on the results of a standardized radiographic examination of 167 SGC horses with a mean age of 14 months. The heritabilities linearly estimated and transformed onto the liability scale were for OC in fetlock joints 0.16 and for OC in hock joints 0.04. Considering fetlock and hock OC together, results in a heritability of 0.17. Palmar/plantar osseus fragments of the fetlock joints showed a heritability of 0.48. We concluded that there is most likely a genetic component in the variation of the development of osteochondrosis in fetlock and hock joints as well as for palmar/plantar osseus fragments of fetlock joints of the investigated population of SGC horses.     

Genome-wide association studies of preweaning growth and in vivo carcass composition traits in Esme sheep

Sheep are considered as a major contributor of global food security. Moreover, sheep preweaning growth traits as well as in vivo carcass composition traits such as ultrasonic measurements of Longissimus dorsi muscle depth (UMD) and back-fat thickness (UFD) are crucially important indicators of meat yield and hot carcass composition. Despite their relative importance for productivity and profitability of a sheep production system, detected QTL for these traits are quite scarce. Therefore, we implemented GWAS for these traits using animal mixed model-based association approach provided by GenABEL in Esme sheep. Three genome-wide and 14 individual chromosome-wide associated SNPs were discovered. As a result, ESRP1, LOC105613082, ZNF641, DUSP5, TEAD1, SMOX, PTPRT, RALYL, POM121C, PHIP, LOC101106051, ZIM3, PEG3, TRPC7, FBXL4, LOC105610397, LOC105616489 and DNAAF2 were suggested as candidates. Some of the discovered genes and involved pathways were already annotated to contribute growth and development in various species including human, mice and cattle. All in all, the results of this study are expected to strongly contribute to shed a light on the underlying molecular mechanisms behind growth and carcass composition traits, with potential implications on studies aiming faster genetic improvement, targeted low-resolution SNP panel designs and genome-editing studies.     

Genome-wide association study for age at puberty in young Nelore bulls

Selection for bulls that would reach puberty early reduces the generation interval and increases fertility and herd productivity. Despite its economic importance, there are few QTL associated with age at puberty described in the literature. In this study, a weighted single-step genome-wide association study was performed to detect genomic regions and putative candidate genes related to age at puberty in young Nelore bulls. Several protein-coding genes related to spermatogenesis functions were identified within the genomic regions that explain more than 0.5% of the additive genetic variance for age at puberty in Nelore bulls, such as ADAM11, BRCA1, CSNK2A, CREBBP, MEIOC, NDRG2, NECTIN3, PARP2, PARP9, PRSS21, RAD51C, RNASE4, SLX4, SPA17, TEX14, TIMP2 and TRIP13 gene. Enrichment analysis by DAVID also revealed several GO terms related to spermatogenesis such as DNA replication (GO:0006260), male meiosis I (GO:0007141), double-strand break repair (GO:0006302), base excision repair (GO:0006284), apoptotic process (GO:0006915), cell–cell adhesion (GO: 0098609) and focal adhesion (GO:0005925). The heritability for age at puberty shows that this trait can be improved based on traditional EBV selection. Adding genomic information to the system helps to elucidate genes and molecular mechanisms controlling the sexual precocity and could help to predict sexual precocity in Nelore bulls with greater accuracy at younger age, which would speed up the breeding programme for this breed.     

蒺藜苜蓿耐酸铝性状的全基因组关联分析

铝毒害是酸性土壤耕种的主要限制因素,每年造成大量作物减产。蒺藜苜蓿是紫花苜蓿的一年生近缘种,广泛分布于世界各地,是紫花苜蓿遗传改良的重要基因资源。本研究利用蒺藜苜蓿群体的耐酸铝性状差异,进行全基因组关联分析,筛选蒺藜苜蓿耐酸铝性状相关的遗传位点,共得到58个与蒺藜苜蓿耐酸铝性状相关的SNP标记。对其周围基因进行功能注释分析,发现这些SNP位点主要参与苜蓿的细胞壁、脂质代谢、环境胁迫响应过程、氧化还原反应过程以及小分子转运等过程。最后,通过基因组选择方法将发掘SNP标记应用到蒺藜苜蓿耐酸铝性状的预测,预测准确性达到0.80,这说明本研究发掘的SNP标记可以用于蒺藜苜蓿及其近缘物种紫花苜蓿耐酸铝性状的遗传改良。     

Pharmacokinetic studies on tobramycin in horses

The objective of the study was to evaluate the pharmacokinetics of tobramycin in plasma and urine in the horse (n = 7) after intravenous administration of a dose of 4 mg/kg b.w. Plasma tobramycin concentrations were assayed microbiologically and by means of HPLC analyses. Pharmacokinetic parameters, calculated on the basis of concentrations determined with the microbiological assay were not statistically different from those obtained when data from HPLC analysis were used, but the microbiological assay was more sensitive in the detection of low plasma and urine values. The values of the total body clearance (Cl(B)) were 101.4 +/- 30.1 and 130.0 +/- 49.9 mL/kg/h, respectively. The overall extraction ratio was 2.9%. The determined capacity of elimination of tobramycin in horses was similar to those for other aminoglycosides. Within 24 h after treatment, 57.6 +/- 12.2% of injected antibiotic was excreted in the urine.     

Pharmacokinetic studies of theophylline in horses

Ingvast-Larsson, C, Paalzow, G., Paalzow, L., Ottosson, T., Lindholm, A. & Appelgren, L.E. Pharmacokinetic studies of theophylline in horses. J. vet. Pharmacol. Therap. 8, 76–81.
The pharmacokinetics of theophylline were determined in Standardised trotters after single intravenous and oral administration. A bi-exponential equation was fitted to the intravenous data and a tri-exponential equation to the oral data. The biological half-life of theophylline was found to be 14.8 h, the volume of distribution 1.02 l/kg and the total plasma clearance 0.86 ml/kg/min. The oral absorption of the drug was complete (bioavailability 108%) and rapid (absorption half-life 0.4 h).
Professor L. E. Appelgren, Department of Pharmacology and Toxicology, Biomedicum. Box 573, S-75J 23 X'ppsala, Sweden.     

Estimation of genetic parameters for racing speed at different distances in young and adult Spanish Trotter horses using the random regression model

A total of 71 522 records (from 3154 horses) with the times per kilometre (TPK), recorded in Spanish Trotter horses (individual races) from racing performances held from 1991 to 2007, were available for this study. The TPK values for the different age groups (young and adult horses) and different distances (1600–2700 m) were considered as different traits, and a bi character random regression model (RRM) was applied to estimate the (co)variance components throughout the trajectory of age groups and distances. The following effects were considered as fixed: the combination of hippodrome‐date of race (404 levels); sex of the animals (3 levels); type of start (2 levels) and a fixed regression of Legendre polynomials (order 2). Those considered as random effects were the random regression Legendre polynomial (order 1) for animals (9201 animals in the pedigree); the individual environment permanent (3154 animals with data) and the driver (n = 957 levels). The residual variance was considered as heterogeneous with two classes (ages). The heritability estimated by distance ranged from 0.12 to 0.34, with a different trajectory for the two age groups. Within each age group, the genetic correlations between adjacent distances were high (>0.90), but decreased when the differences between them were over 400 metres for both age groups. The genetic correlations for the same distance across the age groups ranged from 0.47 to 0.78. Accordingly, the analysed trait (TPK) can be considered as positive genetic correlated but as different traits along the trajectory of distance and age. Therefore, some re‐ranking should be expected in the breeding value of the horses at different characteristics of the racing. The use of RRM is recommended because it allows us to estimate the breeding value along the whole trajectory of race competition.