S. S. Moore

Assessment of positional candidate genes myf5 and igf1 for growth on bovine chromosome 5 in commercial lines of Bos taurus.

Quantitative trait loci for growth traits in beef cattle have been previously reported and fine-mapped in three chromosomal regions of 0 to 30 cM, 55 to 70 cM, and 70 to 80 cM of bovine chromosome 5. In this study, we further examined the association between gene-specific single nucleotide polymorphisms (SNP) of two positional candidate genes, bovine myogenic factor 5 (myf5) and insulin-like growth factor-1 (igf1), in the QTL regions and the birth weight (BWT), preweaning average daily gain (PWADG), and average daily gain on feed (ADGF) in commercial lines of Bos taurus. The QTL regions for the growth traits identified using a haplotype association analysis, which included the gene-specific SNP markers for both genes in this study, were in agreement with previous studies. The gene-specific SNP marker association analysis indicated that the SNP in myf5 had a significant additive effect on PWADG in the M1 line of Beefbooster Inc. (P < 0.10), and a significant additive effect (P < 0.05) and a significant dominance effect (P < 0.10) on ADGF in the M3 line of Beefbooster Inc. When the data from the two commercial lines were pooled, the SNP in myf5 showed a significant association with PWADG (P < 0.10) and with ADGF (P < 0.05). The association between the SNP and BWT, however, did not reach a significance level in the M1 line, the M3 line, or across the lines. For igf1, no significant association between the SNP and the growth traits was detected in either the M1 line or the M3 line, whereas there was only a significant dominance effect (P < 0.10) on BWT detected for the SNP in igfl when the data from the two commercial lines were pooled. These results suggest that myf5 is a strong candidate gene that influences PWADG and ADGF in beef cattle. The SNP of igf1 may not be a causative or close to the causative mutation that affects the three growth traits in the populations of beef cattle examined in this study. Other SNP of igf1 and myf5 or other genes in their respective chromosomal regions, however, should also be studied.

Molecular basis for residual feed intake in beef cattle.

Feed provision is one of the greatest costs of beef production and, with the increasing costs of feed, will remain so for the foreseeable future. Improvement in efficiency has the potential to not only increase profits for cattle producers, but also to decrease the environmental footprint of beef cattle production. Both are important in addressing the challenges of increasing feed costs and land pressure. Residual feed intake (RFI) has increasingly become the measure of choice when evaluating feed efficiency in beef cattle, especially because it is independent of growth and BW. The main inhibitor to adoption of RFI remains the cost and technical difficulty in measuring the trait. This makes RFI a prime candidate for marker-assisted selection because the trait is moderately heritable and DNA or other predictive markers could be used in selection schemes. Although multiple markers have been described over several studies, no major gene affecting RFI has been found. However, a combination of genetic markers, when examined jointly, can explain a large proportion of the genetic variation. Two main barriers remain before full adoption of markers for genetic evaluation and marker-assisted selection can be implemented. First, the genetic interaction of genes affecting RFI on other traits is, as yet, not fully understood. Second the numbers of animals with high quality estimates of RFI remains small. However, current developments indicate that these challenges will soon be overcome.

Whole genome single nucleotide polymorphism associations with feed intake and feed efficiency in beef cattle.

Feed intake and efficiency are economically important traits because feed is the greatest variable cost in beef production. Feed efficiency can be measured as residual feed intake (RFI), which is the difference between actual DMI of an animal and the expected DMI based on its BW and growth rate. Feed conversion ratio (FCR) is the inverse of gross feed efficiency and is the ratio of DMI to ADG. A total of 2,633 SNP across the 29 bovine autosomes were analyzed in 464 steers sired by Angus, Charolais, or Alberta Hybrid bulls for associations with RFI. A total of 150 SNP were associated with RFI at P < 0.05 of which 23 were significant at P < 0.01. Nine of the SNP pairs show high linkage disequilibrium (r(2) > 0.80), so only 1 of the SNP pairs was used in further multiple-marker analyses. Two methods were used to create a panel of SNP that were maximally informative for RFI based on the data. In the first method, 141 unique SNP were combined in a single multivariate model and a backward elimination model was used to drop SNP until all SNP left in the model were significant at P < 0.05. The SNP had greater effects when combined in the multivariate model than when tested individually. In the second method, the estimates from the 141 SNP were used to create a sequential molecular breeding value (MBV) according to the compound covariate prediction (CCP) procedure. The sequential MBV was built by adding the estimated effects one at a time, but only keeping SNP effects in the sequential MBV if the test statistic and the proportion of variance explained were improved. Predictabilities of the 2 methods were compared by regressing RFI on a final MBV created from SNP that remained in each analytical model. The MBV from the compound covariate prediction model produced an r(2) of 0.497, whereas the multivariate model MBV had a decreased r(2) of 0.416. The significant SNP were also tested for associations with DMI and FCR. The SNP showed different combinations of associations with the 4 traits, including some that were only associated with RFI. About 9.5% of the SNP from the 2 models were within 5 cM of previously identified RFI QTL and pinpoint areas to further explore for positional candidate genes. In conclusion, this study has identified a panel of SNP with significant effects on RFI that need to be validated in an independent population and provides continued progress toward selecting markers for use in marker-assisted selection for feed efficiency in beef cattle.

Fine mapping quantitative trait loci for feed intake and feed efficiency in beef cattle

Feed intake and feed efficiency are economically important traits in beef cattle because feed is the greatest variable cost in production. Feed efficiency can be measured as feed conversion ratio (FCR, intake per unit gain) or residual feed intake (RFI, measured as DMI corrected for BW and growth rate, and sometimes a measure of body composition, usually carcass fatness, RFI(bf)). The goal of this study was to fine map QTL for these traits in beef cattle using 2,194 markers on 24 autosomes. The animals used were from 20 half-sib families originating from Angus, Charolais, and University of Alberta Hybrid bulls. A mixed model with random sire and fixed QTL effect nested within sire was used to test each location (cM) along the chromosomes. Threshold levels were determined at the chromosome and genome levels using 20,000 permutations. In total, 4 QTL exceeded the genome-wise threshold of P < 0.001, 3 exceeded at P < 0.01, 17 at P < 0.05, and 30 achieved significance at the chromosome-wise threshold level (at least P < 0.05). No QTL were detected on BTA 8, 16, and 27 above the 5% chromosome-wise significance threshold for any of the traits. Nineteen chromosomes contained RFI QTL significant at the chromosome-wise level. The RFI(bf) QTL results were generally similar to those of RFI, the positions being similar, but occasionally differing in the level of significance. Compared with RFI, fewer QTL were detected for both FCR and DMI, 12 and 4 QTL, respectively, at the genome-wise thresholds. Some chromosomes contained FCR QTL, but not RFI QTL, but all DMI QTL were on chromosomes where RFI QTL were detected. The most significant QTL for RFI was located on BTA 3 at 82 cM (P = 7.60 x 10(-5)), for FCR on BTA 24 at 59 cM (P = 0.0002), and for DMI on BTA 7 at 54 cM (P = 1.38 x 10(-5)). The RFI QTL that showed the most consistent results with previous RFI QTL mapping studies were on BTA 1, 7, 18, and 19. The identification of these QTL provides a starting point to identify genes affecting feed intake and efficiency for use in marker-assisted selection and management.

Genome Sequence and Assembly of Bos indicus

Cattle are divided into 2 groups referred to as taurine and indicine, both of which have been under strong artificial selection due to their importance for human nutrition. A side effect of this domestication includes a loss of genetic diversity within each specialized breed. Recently, the first taurine genome was sequenced and assembled, allowing for a better understanding of this ruminant species. However, genetic information from indicine breeds has been limited. Here, we present the first genome sequence of an indicine breed (Nellore) generated with 52X coverage by SOLiD sequencing platform. As expected, both genomes share high similarity at the nucleotide level for all autosomes and the X chromosome. Regarding the Y chromosome, the homology was considerably lower, most likely due to uncompleted assembly of the taurine Y chromosome. We were also able to cover 97% of the annotated taurine protein-coding genes.

A whole genome scan to map QTL for milk production traits and somatic cell score in Canadian Holstein bulls.

The detection and mapping of genetic markers linked to quantitative trait loci (QTL) can be utilized to enhance genetic improvement of livestock populations. With the completion of the bovine genome sequence assembly, single nucleotide polymorphisms (SNP) assays spanning the whole bovine genome and research work on large scale identification, validation and analysis of genotypic variation in cattle has become possible. The objective of the present study was to perform a whole genome scan to identify and map QTL affecting milk production traits and somatic cell scores using linkage disequilibrium (LD) regression and 1536 SNP markers. Three and 18 SNP were found to be associated with only milk yield (MY) at a genome and chromosome wise significance (p < 0.05) level respectively. Among the 21 significant SNP, 16 were in a region reported to have QTL for MY in other dairy cattle populations and while the rest five were new QTL finding. Four SNP out of 21 are significant for the milk production traits (MY, fat yield, protein yield (PY), and milk contents) in the present study. Six and nine SNP were associated with PY at a genome and chromosome wise significant (p < 0.05) level respectively. Three and 17 SNP were found to be associated with FY at a genome and chromosome wise significant (p < 0.05) level. Five and seven SNP were mapped with somatic cell score at a genome and chromosome wise significant (p < 0.05) level respectively. The results of this study have revealed QTL for MY, PY, protein percentage, FY, fat percentage, somatic cell score and persistency of milk in the Canadian dairy cattle population. The chromosome regions identified in this study should be further investigated to potentially identify the causative mutations underlying the QTL.

Identification of polymorphisms influencing feed intake and efficiency in beef cattle

Feed efficiency is an economically important trait in beef cattle. Net feed efficiency, measured as residual feed intake (RFI), is the difference between actual feed intake and the predicted feed intake required for maintenance and gain of the animal. SNPs that show associations with RFI may be useful quantitative trait nucleotides for marker-assisted selection. This study identified associations between SNPs underlying five RFI QTL on five bovine chromosomes (BTA2, 5, 10, 20 and 29) with measures of dry matter intake (DMI), RFI and feed conversion ratio (FCR) in beef cattle. Six SNPs were found to have effects on RFI (P < 0.05). The largest single SNP allele substitution effect for RFI was -0.25 kg/day located on BTA2. The combined effects of the SNPs found significant in this experiment explained 6.9% of the phenotypic variation of RFI. Not all the RFI SNPs showed associations with DMI and FCR even though these traits are highly correlated with RFI (r = 0.77 and r = 0.62 respectively). This shows that these SNPs may be affecting the underlying biological mechanisms of feed efficiency beyond feed intake control and weight gain efficiency. These SNPs can be used in marker-assisted selection but first it will be important to verify these effects in independent populations of cattle.

A Whole-Genome Scan to Map Quantitative Trait Loci for Conformation and Functional Traits in Canadian Holstein Bulls

Genetic improvement of livestock populations can be achieved through detection and mapping of genetic markers linked to quantitative trait loci (QTL). With the completion of the bovine genome sequence assembly, single nucleotide polymorphism (SNP) assays spanning the whole bovine genome and research work on large-scale identification, validation, and analysis of genotypic variation in cattle has become possible. A total of 462 Canadian Holstein Bulls were used to test the association between SNP and QTL. Single locus linkage disequilibrium regression model was implemented to perform a whole genome scan to identify and map QTL affecting conformation and functional traits. One thousand five hundred thirty-six SNP markers from introns and exons of potential QTL regions for economically important traits across the bovine genome were selected for association analysis. A total of 45 and 151 SNP were found to be associated with 17 conformation and functional traits at a genome- and chromosome-wise significance level, respectively. Among the 196 significant SNP, 169 of them are newly detected in this study, whereas 27 of them have been reported in previous literature and 161 of these were located in genes and are worth further investigating to potentially identify the causative mutations underlying the QTL. The single locus linkage disequilibrium regression method using SNP marker genotypes has proven to be a successful methodology for detecting and mapping QTL in dairy cattle populations.

Linkage disequilibrium and signatures of selection on chromosomes 19 and 29 in beef and dairy cattle.

The objective of this study was to quantify the extent of linkage disequilibrium (LD) on bovine chromosomes 19 and 29 and to study the pattern of selection signatures in beef and dairy breeds (Angus and Holstein) of Bos taurus. The extent of LD was estimated for 370 and 186 single nucleotide polymorphism markers on BTA19 and 29 respectively using the square of the correlation coefficient (r2) among alleles at pairs of loci. A comparison of the extent of LD found that the decline of LD followed a similar pattern in both breeds. We observed long-range LD and found that LD dissipates to background levels at a locus separation of about 20 Mb on both chromosomes. Along each chromosome, patterns of LD were variable in both breeds. We find that a minimum of 30 000 informative and evenly spaced markers would be required for whole-genome association studies in cattle. In addition, we have identified chromosomal regions that show some evidence of selection for economically important traits in Angus and Holstein cattle. The results of this study are of importance for the design and application of association studies.

Transcriptome analysis of subcutaneous adipose tissues in beef cattle using 3′ digital gene expression-tag profiling 1

The molecular mechanisms that regulate fat deposition in bovine adipose tissue have not been well studied. To elucidate the genes and gene networks involved in bovine fat development, transcriptional profiles of backfat (BF) tissues from Hereford × Aberdeen Angus (HEAN, n = 6) and Charolais × Red Angus (CHRA, n = 6) steers with high or low BF thickness were characterized by digital gene expression-tag profiling. Approximately 9.8 to 21.9 million tags were obtained for each library, and a total of 18,034 genes were identified. In total, 650 genes were found to be differentially expressed, with a greater than 1.5-fold difference between the 2 crossbreds (Benjamini-Hochberg false discovery rate ≤ 0.05). The majority of differentially expressed genes that were more highly expressed in CHRA vs. HEAN were associated with development, whereas the differentially expressed genes with greater expression in HEAN vs. CHRA were overrepresented in biological processes such as metabolism and immune response. Thirty-six and 152 differentially expressed genes were detected between animals with high (n = 3) and low (n = 3) BF thickness in HEAN and CHRA, respectively (Benjamini-Hochberg false discovery rate ≤0.05). The differentially expressed genes between high and low groups in CHRA were related to cell proliferation and development processes. In addition, lipid metabolism was 1 of the top 5 molecular and cellular functions identified in both crossbreds. Ten and 17 differentially expressed genes were found to be involved in fat metabolism in HEAN and CHRA, respectively. Genes associated with obesity, such as PTX3 (pentraxin 3, long) and SERPINE1 (serpin peptidase inhibitor, clade E, member 1), were more highly expressed (P < 0.05) in the subset of CHRA animals with greater BF thickness. Our study revealed that the expression patterns of genes in BF tissues differed depending on the genetic background of the cattle.