Progress 05/15/06 to 05/14/10
Outputs
OUTPUTS: The objectives of this proposal were to: 1) Generate genotypic data for 1200 bulls. 2) Infer haplotypes for bulls genotyped, create Holstein specific hapmap, and provide genotypic data to the bovine hapmap project. 3) Develop statistical methods and infrastructure to implement genomic selection and to integrate the genomic data into the national genetic evaluation system. Because Dr. Jerry Taylor at the University of Missouri had also been funded by the NRI to perform a SNP-based mapping project in cattle, we formed a Consortium (known as the iBMC Consortium) to pool resources and develop an Illumina 50K SNP iSelect Infinium assay for cattle. We postulated that the development of this tool would provide an important resource for the livestock genomics community while simultaneously allowing us to meet all project objectives. Because there were insufficient SNPs developed by the public bovine genome sequencing project that were evenly distributed within the bovine genome and that had high probabilities of converting to real SNP with which to develop a bovine 50K SNP assay, we first performed a de novo SNP discovery project using reduced representation of pooled DNA libraries from Angus, Holstein and mixed beef breeds. These libraries were deep sequenced using an Solexa 1G Analyzer and the analysis of the 71 million produced sequences led to the identification of 62,042 putative SNP for which allele frequencies were simultaneously estimated. Algorithms were developed to identify putative SNP from the high-throughput sequence data with a goal of generating highly reliable SNP with high minor allele frequencies. By genotyping 23,521 SNPs in 66 individuals we demonstrated that 91% of the SNPs were real and that the correlation between sequence and genotype determined allele frequencies was 66%. Because of this success, collaborative efforts have been initiated with the National Cancer Institute's Advanced Biomedical Computing Center for additional software developed and public deployment of this approach. The SNPs derived by the consortium were pooled with other publicly available sources of SNPs and were used to design the Illumina BovineSNP50 assay which has probes for 58,366 SNPs. Algorthms were developed to optimally identify SNPs for the assay based on balancing number of beads needed per SNP genotyped, expected conversion of putative SNPs to informative assays, and genome location. After genotyping samples from Holstein, Angus, Limousin, Hereford, Gelbvieh and Charolais cattle at all iBMC sites, we have arrived at a consensus set of 53,272 SNP which are scoreable and produce high quality genotypes. We have been able to increase the numbers of animals that will be genotyped in this project from 1200 to over 5,000. This has arisen due to the ability to pool data produced by three NRI funded projects (PIs: Taylor, Van Tassell and Schnabel) and due to the assay pricing provided to the iBMC Consortium for the BovineSNP50 assay. PARTICIPANTS: University of Illinois: Dr. Larry Schook (pig SNP chip development). University of Missouri: Drs. Jerry Taylor and Bob Schnabel (iBMC Consortium). University of Pennsylvania: Dr. Bob Whitlock (genetics of resistance to Johne's disease). USDA/USMARC: Drs. Tim Smith, Mark Allan and Warren Snelling (iBMC Consortium). Washington State University: Dr. Holly Neibergs (genetics of resistance to Johne's disease). TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Collaboration with other USDA NRI funded PDs and with groups interested in developing a high density SNP genotyping platform for cattle has led to the development of a reagent that will see widespread use within the international livestock genome research community. Over 1,000,000 sample assays were purchased for use in research and application globally. This platform quickly became the de facto standard and has been used for many genome mapping projects in cattle. This platform is also provided utility in application of whole genome enabled animal selection in beef and dairy cattle. The US dairy industry has embraced this technology and the USDA national dairy cattle evaluation officially included genomic data in the January 2009 release.
Publications
- Hayes B.J., Bowman A.J., Chamberlain A.J., Savin K., Van Tassell C.P., Sonstegard T.S., Goddard M.E. 2009. A Validated Genome Wide Association Study to Breed Cattle Adapted to an Environment Altered by Climate Change. PLoS One 2009 Aug 18;4(8):e6676.
- Decker J.E., Pires J.C., Conant G.C., McKay S.D., Heaton M.P., Chen K., Cooper A., Vilkki J., Seabury C.M., Caetano A.R., Johnson G.S., Benneman R.A., Hanotte O., Eggert L.S., Wiener P., Kim J.J., Kim K.S., Sonstegard T.S., Van Tassell C.P., Neibergs H.L., McEwan J.C., Braunig R., Coutinho L.L., Babar M.E., Wilson G.A., McClure M.C., Rolf M.M., Kim J., Schnabel R.D., Taylor J.F. 2009. Resolving the evolution of extant and extinct ruminants with high-throughput phylogenomics. Proc Natl Acad Sci USA, 106:18644-18649
- Ramos A.M., Crooijmans R.P.M.A., Affara N.A., Amaral A.J., Archibald A.L., Beever J.E., Bendixen C., Churcher C., Clark R., Dehais P., Hansen M.S. Hedegaard, J., Hu Z.L., Kerstens H.H., Law A.S., Megens H.J., Milan D., Nonneman D.J., Rohrer G.A., Rothschild M.F., Smith T.P.L., Schnabel R.D., Van Tassell C.P., Taylor J.F., Wiedmann R.T., Schook L.B. Groenen, M.A.M. 2009. PLoS One 4(8):E6524. p. 1-13
- Weigel K.A., Van Tassell C.P., O'Connell J.R., VanRaden P.M., Wiggans G.R. 2010. Prediction of unobserved single nucleotidepolymorphism genotypes of Jersey cattle usingreference panels and population-basedimputation algorithms. J. Dairy Sci. 93:2229-2238
- Wiggans G.R., Sonstegard T.S., VanRaden P.M., Matukumalli L.K., Schnabel R.D., Taylor J.F., Schenkel F.S. & Van Tassell C.P. 2009. Selection of single-nucleotide polymorphisms and quality of genotypes used in genomic evaluation of dairy cattle in the United States and Canada. Journal of Dairy Science 92:3431-3436
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Progress 05/15/08 to 05/14/09
Outputs
OUTPUTS: The objectives of this proposal were to: 1) Generate genotypic data for 1200 bulls. 2) Infer haplotypes for bulls genotyped, create Holstein specific hapmap, and provide genotypic data to the bovine hapmap project. 3) Develop statistical methods and infrastructure to implement genomic selection and to integrate the genomic data into the national genetic evaluation system. Because Dr. Jerry Taylor at the University of Missouri had also been funded by the NRI to perform a SNP-based mapping project in cattle, we formed a Consortium (known as the iBMC Consortium) to pool resources and develop an Illumina 50K SNP iSelect Infinium assay for cattle. We postulated that the development of this tool would provide an important resource for the livestock genomics community while simultaneously allowing us to meet all project objectives. Because there were insufficient SNPs developed by the public bovine genome sequencing project that were evenly distributed within the bovine genome and that had high probabilities of converting to real SNP with which to develop a bovine 50K SNP assay, we first performed a de novo SNP discovery project using reduced representation of pooled DNA libraries from Angus, Holstein and mixed beef breeds. These libraries were deep sequenced using an Solexa 1G Analyzer and the analysis of the 71 million produced sequences led to the identification of 62,042 putative SNP for which allele frequencies were simultaneously estimated. Algorithms were developed to identify putative SNP from the high-throughput sequence data with a goal of generating highly reliable SNP with high minor allele frequencies. By genotyping 23,521 SNPs in 66 individuals we demonstrated that 91% of the SNPs were real and that the correlation between sequence and genotype determined allele frequencies was 66%. Because of this success, collaborative efforts have been initiated with the National Cancer Institute's Advanced Biomedical Computing Center for additional software developed and public deployment of this approach. The SNPs derived by the consortium were pooled with other publicly available sources of SNPs and were used to design the Illumina BovineSNP50 assay which has probes for 58,366 SNPs. Algorthms were developed to optimally identify SNPs for the assay based on balancing number of beads needed per SNP genotyped, expected conversion of putative SNPs to informative assays, and genome location. After genotyping samples from Holstein, Angus, Limousin, Hereford, Gelbvieh and Charolais cattle at all iBMC sites, we have arrived at a consensus set of 53,272 SNP which are scoreable and produce high quality genotypes. We have been able to increase the numbers of animals that will be genotyped in this project from 1200 to over 5,000. This has arisen due to the ability to pool data produced by three NRI funded projects (PIs: Taylor, Van Tassell and Schnabel) and due to the assay pricing provided to the iBMC Consortium for the BovineSNP50 assay. PARTICIPANTS: University of Illinois: Dr. Larry Schook (pig SNP chip development). University of Missouri: Drs. Jerry Taylor and Bob Schnabel (iBMC Consortium). University of Pennsylvania: Dr. Bob Whitlock (genetics of resistance to Johne's disease). USDA/USMARC: Drs. Tim Smith, Mark Allan and Warren Snelling (iBMC Consortium). Washington State University: Dr. Holly Neibergs (genetics of resistance to Johne's disease). TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Collaboration with other USDA NRI funded PDs and with groups interested in developing a high density SNP genotyping platform for cattle has led to the development of a reagent that will see widespread use within the international livestock genome research community. Over 20,000 sample assays were purchased by members of the iBMC Consortium as part of the platform development project with Illumina and genotyping with these reagents has almost been completed. This platform will be used for the foreseeable future for many genome mapping projects in cattle and it will also provide the initial platform for evaluating the utility of whole genome enabled animal selection in beef and dairy cattle.
Publications
- Bovine Genome Sequencing and Analysis Consortium. 2009. The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science. 324(5926):522-8.
- Bovine HapMap Consortium. 2009. Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds. Science. 324(5926):528-32.
- Matukumalli, L.K., Lawley, C.T., Schnabel, R.D., Taylor, J.F., Allan, M.F., Heaton, M.P., O'Connell, J., Moore, S.S., Smith, T.P., Sonstegard, T.S., Van Tassell, C.P. 2009. Development and characterization of a high density SNP genotyping assay for cattle. PLoS ONE. 4(4):e5350.
- Decker, J.E., Pires, J.C., Conant, G.C., McKay, S.D., Heaton, M.P., Chen, K., Cooper, A., Vilkki, J., Seabury, C.M., Caetano, A.R., Johnson, G.S., Brenneman, R.A., Hanotte, O., Eggert, L.S., Wiener, P., Kim, J.J., Kim, K.S., Sonstegard, T.S., Van Tassell, C.P., Neibergs, H.L., McEwan, J.C., Brauning, R., Coutinho, L.L., Babar, M.E., Wilson, G.A., McClure, M.C., Rolf, M.M., Kim, J., Schnabel, R.D., and Taylor, J.F. 2009. Resolving the evolution of extant and extinct ruminants with high-throughput phylogenomics. Proceedings of the National Academy of Sciences. 106(44):18644-9.
- Wiggans, G.R., Sonstegard, T.S., VanRaden, P.M., Matukumalli, L.K., Schnabel, R.D., Taylor, J.F., Schenkel, F.S., Van Tassell, C.P. 2009. Selection of single-nucleotide polymorphisms and quality of genotypes used in genomic evaluation of dairy cattle in the United States and Canada. J. Dairy Sci. 92(7):3431-6.
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Progress 05/15/07 to 05/14/08
Outputs
OUTPUTS: Over 25 million 25 bp Solexa reads were generated using reduced representation DNA libraries. Over 80,000 novel SNP were identified. Over 25,00 of those were used to design and construct a high density SNP genotyping assay that has been commercialized by Illumina as the BovineSNP50 genotyping assay. PARTICIPANTS: Participants: Drs. Curt Van Tassell (PD), Tad Sonstegard and Lakshmi Matukumalli, George Wiggans (Co-PD) (iBMC Consortium). Collaborators: Drs. Jerry Taylor and Bob Schnabel (University of Missouri - iBMC Consortium); Drs. Tim Smith, Mark Allan and Warren Snelling (USDA/USMARC -iBMC Consortium) TARGET AUDIENCES: This project has impacted both scientists and dairy industry partners. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
The objectives of this grant proposal were to generate genotypic data on 10,000 SNP for 1,200 Holstein bulls, create a Holstein-specific HapMap, and then provide genotypic data to the bovine HapMap project. This objective was met. Over 15,000 Holsteins (more than 10,000 by our lab) have been genotyped using this assay. Genotypic data for HapMap population will be released publically upon publication of the manuscript derived from those data. The final objective is to develop statistical methods and infrastructure to implement genomic selection and to combine the genetic merit prediction using genomic data with results from the national genetic evaluation system. This objective has been largely met. Genetic predictions are currently generated for Holsteins using SNP data.
Publications
- Van Tassell CP, Smith TPL, Matukumalli LK, Taylor JF, Schnabel RD, Lawley CT, Haudenchild CD, Moore SS, Warren WC and Sonstegard TS. 2008. Simultaneous SNP discovery and allele frequency estimation by high throughput sequencing of reduced representation genomic libraries. Nature Methods. 5:247-252 cover article.
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Progress 05/15/06 to 05/14/07
Outputs
OUTPUTS: Because Dr. Jerry Taylor at the University of Missouri had also been funded by the NRI to perform a SNP-based mapping project in cattle, we formed a Consortium (known as the iBMC Consortium) to pool resources and develop an Illumina 50K SNP iSelect Infinium assay for cattle. We postulated that the development of this tool would provide an important resource for the livestock genomics community while simultaneously allowing us to meet all project objectives. Because there were insufficient SNPs developed by the public bovine genome sequencing project that were evenly distributed within the bovine genome and that had high probabilities of converting to real SNP with which to develop a bovine 50K SNP assay, we first performed a de novo SNP discovery project using reduced representation of pooled DNA libraries from Angus, Holstein and mixed beef breeds. These libraries were deep sequenced using an Solexa 1G Analyzer and the analysis of the 71 million produced sequences led to
the identification of 62,042 putative SNP for which allele frequencies were simultaneously estimated. Algorithms were developed to identify putative SNP from the high-throughput sequence data with a goal of generating highly reliable SNP with high minor allele frequencies. By genotyping 23,521 SNPs in 66 individuals we demonstrated that 91% of the SNPs were real and that the correlation between sequence and genotype determined allele frequencies was 66%. Because of this success, collaborative efforts have been initiated with the National Cancer Institute's Advanced Biomedical Computing Center for additional software development and the public deployment of this software. The SNPs derived by the consortium were pooled with other publicly available sources of SNPs and were used to design the Illumina BovineSNP50 assay which has probes for 58,366 SNPs. Algorthms were developed to optimally identify SNPs for the assay based on balancing number of beads needed per SNP genotyped, expected
conversion of putative SNPs to informative assays, and genome location. After genotyping samples from Holstein, Angus, Limousin, Hereford, Gelbvieh and Charolais cattle at all iBMC sites, we have arrived at a consensus set of 53,272 loci (may not all be variable) which are scoreable and produce high quality genotypes. We have been able to increase the numbers of animals that will be genotyped in this project from 1200 to over 5,000. This has arisen due to the ability to pool data produced by three NRI funded projects (PIs: Taylor, Van Tassell and Schnabel) and due to the assay pricing provided to the iBMC Consortium for the BovineSNP50 assay.
PARTICIPANTS: University of Illinois: Dr. Larry Schook (pig SNP chip development). University of Missouri: Drs. Jerry Taylor and Bob Schnabel (iBMC Consortium). University of Pennsylvania: Dr. Bob Whitlock (genetics of resistance to Johne's disease). USDA/USMARC: Drs. Tim Smith, Mark Allan and Warren Snelling (iBMC Consortium). Washington State University: Dr. Holly Neibergs (genetics of resistance to Johne's disease).
Impacts
Collaboration with other USDA NRI funded PDs and with groups interested in developing a high density SNP genotyping platform for cattle has led to the development of a reagent that will see widespread use within the international livestock genome research community. Over 20,000 sample assays were purchased by members of the iBMC Consortium as part of the platform development project with Illumina and genotyping with these reagents has almost been completed. This platform will be used for the foreseeable future for many genome mapping projects in cattle and it will also provide the initial platform for evaluating the utility of whole genome enabled animal selection in beef and dairy cattle.
Publications
- No publications reported this period
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