Location: Livestock Bio-Systems2015 Annual Report
Objective 1: Identify genetic markers associated with reproductive performance suitable for use in commercial pigs. -Subobjective 1.A. Identify QTL for novel phenotypic traits associated with female reproductive performance. -1.B. Develop genetic markers in QTL regions that are predictive of phenotype in commercial populations. Objective 2: Identify genetic variation associated with genes affecting female reproductive traits in swine. -Subobjective 2.A. Create a database of genetic variants segregating in the USMARC BX population that are expected to affect gene function. -Subobjective 2.B. Determine if genetic variants from Sub-objective 2A residing in positional candidate genes for validated QTL from Objective 1 are associated with phenotypic variation. Objective 3: Provide the swine industry with the necessary information and tools to implement marker assisted selection for sow reproductive and lifetime performance.
The goal of this research is to ensure US swine producers are a competitive source of pork products by providing the genetic information necessary to maintain superior production levels. The approach will use genetic markers and genomic technologies to understand how the genome regulates animal performance and determine the molecular basis behind non-additive genetic effects. Availability of the draft swine genome sequence will allow continuation of research on genomic regions affecting components of reproductive performance, growth, and carcass quality to move faster and more efficiently. Future studies will include a broader list of phenotypes including metabolic parameters to understand nutrient utilization, animal disposition and incidence of disease during natural outbreaks in the population. This project will use genomic approaches in combination with extensively phenotyped swine populations to identify genetic markers associated with production traits and understand these complex biological processes. Our approach will be to conduct genome-wide QTL scans and then fine map these QTL and develop SNP markers in tight linkage with the causative polymorphisms. QTL scans will be conducted in subsets of the USMARC BX swine population that have been extensively phenotyped for a wide variety of traits. This will permit a more complete biological understanding of each QTL region. Follow-up studies on QTL will be conducted in the BX population on larger groups of animals that may be phenotyped for a specific set of traits. Standard QTL analyses will first be conducted followed by statistical models to identify components to nonadditive genetic variation affecting performance such as intra-locus (dominance and imprinting) and inter-locus (epistatic) interactions. These analyses will also yield valuable information about pleiotropic effects to understand the molecular bases of genetic correlations. A high density SNP map (5-20 SNP/cM) will be developed for the studied regions and genotyped across additional generations of BX animals to fine map QTL. Significant SNP markers developed from these approaches will be evaluated in additional commercially relevant lines of pig to ensure their applicability in commercial pigs. Markers that exhibit useful predictive genetic information will be disseminated to the swine industry. Finally with all of the genetic and phenotypic knowledge in hand, we should be well equipped to determine the causative gene for some QTL and greatly improve our understanding of the physiological effects of these QTL. A precise location of the causative gene as predicted from fine mapping studies, knowledge about different biological pathways affected from the extensively phenotyped population and knowledge about the genes located in the region from the swine genome sequence should allow selection of positional candidate gene to study for causative variation. These studies will be supplemented with functional genomic and marker-assisted animal experimentation.
Significant progress has been made in the past fiscal year. To facilitate QTL discovery and validation, we have genotyped over 600 animals that have contributed progeny in the U.S. Meat Animal Research Center (USMARC) commercial swine population. A process to implement genotypic data imputation was developed. The procedure will permit filling in genotypes for nearly 70,000 single nucleotide polymorphism (SNP) markers for any pig in the USMARC population that has been genotyped with any of the Illumina BeadChip platforms (GGPLD, SNP60.v1, SNP60.v2 or GGPHD). This procedure was originally tested on a data set from the National Pork Board where two different platforms were used (GGPLD and SNP60.v2). Genome-wide association analyses have been completed for the remaining phenotypes collected in the USMARC BX QTL discovery population (mammary gland development and a group of blood marker phenotypes) and analyses are nearly complete for the phenotypes collected in the National Pork Board Gilt Development study. This study has numerous unique phenotypes that are relevant to attainment of puberty and development of the reproductive tract in gilts. Variant calling from an additional 100X coverage of the porcine genome of 36 intermediate parents in the BX population (generations 5 and 6) has been completed. Variants were localized on the current swine genome build (build 10.2). These data have helped verify genetic variants and will be used to create segregating haplotypes in this population. The variant calling in the BX population has permitted identifying potential causative genetic variation in the BX population that can be tested. To this end, approximately 75 potentially functional SNP were tested for their effect on immunocrit values in the current USMARC rotational commercial population. Similarly, 90 putative functional SNP are currently being tested for age at first estrus. Finally, as the current swine genome build 10.2 has regions that need to be corrected, we have launched an effort to create a new genome build using next generation, long-read sequence technologies. The data have been collected (70X genome equivalents) and is currently being assembled. Annotation of this build will be facilitated with expression data collected from seven diverse tissues. The expression data will include evaluating different transcripts for each gene (splice variants, alternative transcriptional start and stop sites, etc.) along with transcript abundance.
1. Genomic locations controlling vertebral development in swine were discovered. While number of vertebrae is highly conserved across most mammalian species, considerable variation exists within pigs and has been linked to production traits. Therefore, ARS scientists at Clay Center, Nebraska, conducted a genome-wide association study for genes affecting number of thoracic and lumbar vertebrae in their commercial swine population. Thirty-one genomic regions were discovered to control at least one trait and these results highlight the importance of the HOX gene families in regulating this critical developmental process. Genetic variation within candidate genes is being studied to further understand how development of the vertebral column is regulated. Genetic markers within these regions would enable the swine industry to modify vertebral numbers in commercial populations.
2. Genome-wide association for age at puberty in pigs reveals common biological mechanisms among mammals. Pigs that reach puberty earlier stay in the herd longer and have a greater productive lifetime. Predictive markers will allow selection for younger age at puberty and desirable traits correlated with sow lifetime productivity. ARS scientists at Clay Center, Nebraska, conducted a genomic study for age at puberty in pigs revealing over 200 DNA marker associations and twenty-seven significant QTL. Eight marker associations confirmed previously identified regions for age at puberty in the pig and twelve loci for age at puberty or body mass index (obesity) in humans. Many of the candidate genes are involved in energy balance and some are associated with fatness in pigs. Six other genes have been associated with puberty in rodents or cattle. Sequence variation in these genes is being evaluated for functional variation in gene action and use as predictive markers for pig production.
Schneider, J.F., Nonneman, D.J., Wiedmann, R.T., Vallet, J.L., Rohrer, G.A. 2014. Genomewide association and identification of candidate genes for ovulation rate in swine. Journal of Animal Science. 92(9):3792-3803.
Schneider, J.F., Miles, J.R., Brown-Brandl, T.M., Nienaber, J.A., Rohrer, G.A., Vallet, J.L. 2015. Genomewide association analysis for average birth interval and stillbirth in swine. Journal of Animal Science. 93(2):529-540.
Selsby, J.T., Ross, J.W., Nonneman, D., Hollinger, K. 2015. Porcine models of muscular dystrophy. ILAR Journal. 56(1):116-126.
Andersson, L., Archibald, A.L., Bottema, C.D., Brauning, R., Burgess, S.C., Burt, D.W., Casas, E., Cheng, H.H., Clarke, L., Couldrey, C., Dalrymple, B.P., Elski, C.G., Foissac, S., Giuffra, E., Groenen, M.A., Hayes, B.J., Huang, L.S., Khatib, H., Kijas, J.W., Kim, H., Lunney, J.K., McCarthy, F.M., McEwan, J.C., Moore, S., Nanduri, B., Notredame, C., Palti, Y., Plastow, G.S., Reecy, J.M., Rohrer, G.A., Sarrapoulou, E., Schmidt, C.J., Silverstein, J., Tellam, R.L., Tixier-Biochard, M., Tosser-Klopp, G., Tuggle, C.K., Vilkki, J., White, S.N., Zhao, S., Zhou, H. 2015. Coordinated international action to accelerate genome-to-phenome with FAANG, The Functional Annotation of Animal Genomes project. Genome Biology. 16:57. DOI:10.1186/S13059-015-0622-4.
Rempel, L.A., Vallet, J.L., Lents, C.A., Nonneman, D.J. 2015. Measurements of body composition during late gestation and lactation in first and second parity sows and its relationship to piglet production and post-weaning reproductive performance. Livestock Science. 178:289-295.
Wiedmann, R.T., Nonneman, D.J., Rohrer, G.A. 2015. Genome-wide copy number variations using SNP genotyping in a mixed breed swine population. PLoS One. 10(7):e0133529. DOI: 10.1371/journal.pone.0133529.
Calderón Díaz, J.A., Vallet, J.L., Lents, C.A., Nonneman, D.J., Miles, J.R., Wright, E.C., Rempel, L.A., Cushman, R.A., Freking, B.A., Rohrer, G.A., Phillips, C., Dedecker, A., Foxcroft, G., Stalder, K.J. 2015. Age at puberty, ovulation rate, and uterine length of developing gilts fed two lysine and three metabolizable energy concentrations from 100 to 260 d of age. Journal of Animal Science. 93(7):3521-3527.
Vallet, J.L., Miles, J.R., Rempel, L.A., Nonneman, D.J., Lents, C.A. 2015. Relationships between day one piglet serum immunoglobulin immunocrit and subsequent growth, puberty attainment, litter size, and lactation performance. Journal of Animal Science. 93(6):2722-2729.
Vallet, J., Calderon, J., Stalder, K., Phillips, C., Bradley, G., Miles, J., Rempel, L., Lents, C., Freking, B., Rohrer, G., Nonneman, D., Cushman, R. 2014. Optimal dietary energy and protein for the development of gilts - NPB #12-209. National Pork Board. Available: http://research.pork.org/FileLibrary/ResearchDocuments/12-209-Vallet-USDA.pdf.