Progress 06/01/04 to 05/31/06
Outputs
Funds provided under LGSI supported the efforts of two international consortia to complete whole-genome physical maps for cattle and swine. Physical sequence-ready maps have been completed for both species. A new third generation radiation hybrid map for cattle was integrated with the BAC fingerprint map produced by the Genome Sequencing Centre in Vancouver, Canada, a critical step for proper assembly of the whole bovine genome sequence created at the Baylor College of Medicine with NIH funding. Genome sequencing has begun for the pig, under leadership at UIUC, and a second generation radiation hybrid map of the pig was completed and included over 2,500 markers. Examples of potential economic impact to date include identification of the ABCG2 gene responsible for major differences among dairy cattle in their ability to produce milk with specific levels of fat and protein. Testing for this gene will allow selection of bulls with superior breeding potential for milk
production traits. The gene for tibial hemimelia in Shorthorn cattle was also mapped, resulting in a genetic test used by the industry to eliminate this economically important congenital abnormality. A candidate gene for hypotrichosis in Hereford cattle was identified. Developing a method to identify carriers in cattle will assist producers in making informed breeding decisions to decrease the occurrence of hypotrichosis in Hereford cattle.
Impacts
The ABCG2 gene was identified as responsible for major differences among dairy cattle in their ability to produce milk with specific levels of fat and protein. Testing for this gene will allow breeders to select bulls with superior breeding potential for milk production traits. The gene for tibial hemimelia in Shorthorn cattle was mapped, resulting in a genetic test used by the industry to eliminate this economically important congenital abnormality. Testing for the mutant allele will assist breeding strategies to reduce the frequency of the unwanted mutation. A candidate gene for the hypotrichosis in Hereford cattle was identified. Developing a method to identify carriers in cattle will assist producers in making informed breeding decisions to decrease the occurrence of hypotrichosis in Hereford cattle.
Publications
- Cohen-Zinder, M., Seroussi, E., Larkin, D.M., Loor, J.J., Everts-van der-Wind, A., Heon-Lee, J., Drackley, J.K., Band, M.R., Shani, M., Lewin, H.A., Weller, J.I. and Ron, M. 2005. Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle. Genome Research 15: 936-944.
- Everts-van der Wind, A., Kata, S., Band, M.R., Rebeiz, M., Larkin, D.M., Everts, R.E., Green, C.A., Liu, L., Natarajan, S., Goldammer, T., Lee, J.H., McKay, S., Womack, J.E. and Lewin, H.A. 2004. A 1,463 gene cattle-human comparative map with anchor points defined by human genome sequence coordinates. Genome Research 14: 1424-1437.
- Everts-van der Wind, A., Larkin, D.M., Green, C.A., Elliott, J.S., Olmstead, C.A., Chiu, R., Schein, J.E., Marra, M.A., Womack, J.E. and Lewin, H.A. 2005. A high-resolution whole-genome cattle-human comparative map reveals details of mammalian chromosome evolution. Proceedings of the National Academy of Sciences (USA), 102: 18526-18531.
- Hamernik, D.L., Lewin, H.A. and Schook, L.B. 2003. Allerton III. Beyond livestock genomics. Animal Biotechnology 14: 77-82.
- Larkin, D.M., Everts-van der Wind, A., Rebeiz, M., Schweitzer, P.A., Bachman, S., Green, C., Wright, C.L., Campos, E.J., Benson, L.D., Edwards, J., Liu, L., Osoegawa, K., Womack, J.E., de Jong, P.E. and Lewin, H.A. 2003. A cattle-human comparative map built with cattle BAC-ends and human genome sequence. Genome Research 13: 1966-1972.
- Lewin, H. A. 2004. The future of cattle genomics: The beef is here. Cytogenetics and Genome Research 102: 10-15.
- Meyers, S.N., Rogatcheva, M.B., Yerle, M., Milan, D., Hawken, R.J., Schook, L.B. and Beever, J.E. 2005. Piggy-BACing the human genome: II. A high-resolution, physically-anchored, comparative map of the porcine autosomes. Genomics 86: 739-752.
- Murphy, W.J., Larkin, D.M., Everts-van der Wind, A., Bourque, G., Tesler, G., Auvil, L., Beever, J.E., Chowdhary, B.P., Galibert, F., Gatzke, L., Hitte, C., Meyers, S.N., Milan, D., Ostrander, E.A., Pape, G., Parker, H.G., Raudsepp, T., Rogatcheva, M.B., Schook, L.B., Skow, L.C., Welge, M., Womack, J.E., O'Brien, S.J., Pevzner, P.A. and Lewin H.A. 2005. Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps. Science 309: 613-617.
- Rogatcheva, M.B., Beever, J.E., He, W.-S., Larkin, D.M., Meyers, S.N., Marron, B.M. and Schook, L.B. 2006. Piggy-BACing the human genome: I. Constructing a porcine physical map through comparative genomics. Animal Genetics (In Press).
- Rogatcheva, M.M., Rund, L.A., Beever, J.E. and Schook, L.B. 2003. Harvesting the genomic promise: Recombineering sequences for phenotypes. Animal Biotechnology 14:103-118.
- Schook, L.B., Beattie, C.W., Beever, J.E., Donovan, S.M., Jamison, R.D., Niemi, S.M., Rothschild, M.F., Rutherford, M.S., Smith, D.M. and Zuckerman, F.A. 2005. Swine in biomedical research: Creating the building blocks of animal models. Animal Biotechnology 16:183-190.
- Schook, L.B., Beever, J.E., Rogers, J., Humphray, S., Archibald A., Chardon, P., Milan, D., Rohrer, G. and Eversole, K. 2005. Swine Genome Sequencing Consortium (SGSC): A strategic roadmap for sequencing the pig genome. Comparative and Functional Genomics 6, 251-255.
- Smith, D.M., Lunney, J.K., Martens, G.W., Ando, A., Lee, J.-H., Ho, C.-S., Schook, L.B., Renard, C. and Chardon, P. 2005. Nomenclature for factors of the SLA class-I system. Tissue Antigens 65:136-149.
- Smith, D.M., Lunney, J.K., Martens, G.W., Ando, A., Lee, J.-H., Ho, C.-S., Schook, L.B., Renard, C. and Chardon, P. 2005. Nomenclature for factors of the SLA class-II system. Tissue Antigens 66:623-639.
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Progress 01/01/05 to 12/31/05
Outputs
To facilitate assembly of the cattle genome sequence, the new Illinois-Texas high-resolution cattle radiation hybrid (RH) map was integrated with the Genome Sciences Centre cattle fingerprint contigs. These maps share 2,328 BAC-end sequences (BESs) on 2,327 BAC clones, which allowed for direct anchoring and ordering of 46% (300 of 655) of fingerprint contigs on the cattle chromosomes. Approximately 90% agreement was found between the order of BAC clones within cattle contigs and BESs on the RH map. The 180 inconsistencies in marker order were flips of adjacent markers (59%) or markers found in positions significantly different between the two maps (41%). Comparison with orthologous markers in the human genome demonstrates that for the majority of flips of adjacent markers the order of markers in the contigs is consistent with the order in the human genome, whereas the RH map shows higher consistency of order with the human genome for out-of-place markers.
Independently, COMPASS (an in silico comparative mapping tool) was utilized for anchoring of 400 cattle fingerprint contigs to the cattle-human and cattle-dog comparative maps. COMPASS cattle chromosome assignments for 300 contigs were compared with anchored positions of the same contigs on the RH map. This comparison showed 99% agreement between the predicted and actual chromosome assignments. In total, the integrated map allows for chromosome assignment of 60% of cattle fingerprint contigs containing 98% of all BAC clones from fingerprint contigs. The integrated map is thus an invaluable tool for the scaffolding the cattle genome sequence onto the cattle chromosomes. For the pig, a second generation radiation hybrid map was completed and included over 2,500 markers. This map also provides a high resolution (< 1 MB) comparison map to humans based on the BESs generated by previous LGSI funding. Over 100,000 BES of BAC fingerprints were used to anchor BAC contigs to support the
strategy to be utilized in the creation of the pig genome minimal tiling path (MTP). The approach that we developed has permitted anchoring fingerprints generated by collaborators around the world and permitted a revised estimate of the pig genome size. Collaborating with colleagues at the Wellcome Trust Sanger Institute we have completed the development of a BAC MTP that will be used for the pig genome sequencing project. This work was the foundation for the successfully funded ($10M) USDA proposal.
Impacts
The ABCG2 gene was identified as responsible for major differences among dairy cattle in their ability to produce milk with specific levels of fat and protein. Testing for this gene will allow breeders to select bulls with superior breeding potential for milk production traits. The gene for tibial hemimelia in Shorthorn cattle was mapped, resulting in a genetic test used by the industry to eliminate this economically important congenital abnormality. Testing for the mutant allele will assist breeding strategies to reduce the frequency of the unwanted mutation. A candidate gene for the hypotrichosis in Hereford cattle was identified. Developing a method to identify carriers in cattle will assist producers in making informed breeding decisions to decrease the occurrence of hypotrichosis in Hereford cattle.
Publications
- Cohen-Zinder, M., E. Seroussi, D. M. Larkin, J. J. Loor, A. Everts-van der Wind, J. H. Lee, J. K. Drackley, M. R. Band, M. Shani, H. A. Lewin, J. I. Weller and M. Ron. 2005. Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and compostion in Holstein Cattle. Genome Research 15:936-944.
- Larkin, D. M., A.Everts-van der Wind, R. Chiu, J. E. Schein, J. S. Elliott, M. A. Marra, J. E. Womack, and H. A. Lewin. 2006. Integration of high-resolution cattle radiation hybrid and fingerprint contig maps. Plant and Animal Genome XIV, San Diego, CA, p232 (abstract)
- Meyers S. N., M. B. Rogatcheva, M. Yerle, D. Milan, R. J. Hawken, L .B. Schook and J. E. Beever. 2005. Piggy-BACing the human genome: II. A high-resolution, physically-anchored, comparative map of the porcine autosomes. Genomics (in press).
- Meyers S.N., T. M Stearns, S. L. Rodriguez-Zas and J. E. Beever, J.E. 2006. Fine-mapping of a pork tenderness QTL on porcine chromosome 2 (SSC2). Plant and Animal Genome XIV, San Diego, CA (abstract)
- Murphy, W. J., D. M. Larkin, A. Everts-van der Wind, G. Bourque, G. Tesler, L. Auvil, J. E. Beever, B. P. Chowdhary, F. Galibert, L. Gatzke, C. Hitte, S. N. Meyers, E. A. Ostrander, G. Pape, H. G. Parker, T. Raudsepp, M. B. Rogatcheva, L. B. Schook, L. C. Skow, M. Welge, J. E. Womack, S. J. OBrien, P. A. Pevzner and H. A. Lewin. 2005. Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps. Science 309:613-617.
- Rogatcheva, M. B., J. E. Beever, W-S He, D. M. Larkin, S. Meyers, B. Marron, and L. B. Schook. 2005. Piggy-BACing the human genome: I. Constructing a porcine physical map through comparative genomics. Animal Genetics (in press).
- Schook, L., C. Beattie, J. Beever, S. Donovan, R. Jamison, S. Niemi, M. Rothschild, M. Rutherford, D. Smith and F. Zuckerman. 2005. Swine in biomedical research: creating the building blocks of animal models. Animal Biotechnology 16:183-190.
- Schook, L. B., J. E. Beever, J. Roger, S. Humphray, A. Archibald, P. Chardon, D. Milan, G. Rohrer and K. Eversole. 2005. Swine Genome Sequencing Consortium (SGSC): a strategic roadmap for sequencing the pig genome. Comparative and Functional Genomics 6, 251-255..
- Smith, D. M., J. K. Lunney, G. W. Martens, A. Ando, J.-H. Lee, C.-S. Ho, L. B. Schook, C. Renard and P. Chardon. 2005. Nomenclature for factors of the SLA class-I system. Tissue Antigens 65:136-149.
- Smith, D. M., J. K. Lunney, G. W. Martens, A. Ando, J.-H. Lee, C.-S. Ho, L. B. Schook, C. Renard and P. Chardon. 2005. Nomenclature for factors of the SLA class-II system. Tissue Antigens 66:623-639.
- Wagner, E.K., S. N. Meyers, M. B. Rogatcheva, D. Milan, L. B. Schook, and J. E. Beever. 2006. A comparative radiation hybrid map of the porcine X chromosome. Plant and Animal Genome XIV, San Diego, CA (abstract)
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Progress 01/01/04 to 12/31/04
Outputs
We previously localized a quantitative trait locus (QTL) on chromosome 6 affecting milk fat and protein concentration to a 4 cM confidence centered on the microsatellite BM143. We characterized the genes and sequence variation in this region, and identified common haplotypes spanning five polymorphic sites in the genes IBSP, SPP1, PKD2, and ABCG2 for two sires segregating for this QTL. Expression of SPP1 and ABCG2 in the bovine mammary gland increased during lactation. SPP1 was fully sequenced, and all the coding exons of ABCG2 and PKD2 were sequenced for these two sires. Only the single nucleotide change capable of encoding a substitution of tyrosine to serine (YS) corresponded to the segregation status of all three heterozygous and 15 homozygous sires for the QTL in the Israeli and U.S. Holstein populations (P = 0.00008). The allele substitution fixed effects on the genetic evaluations of 335 Israeli sires were -340 kg milk, +0.15% fat, and +0.13% protein (F-value =
200). None of the other polymorphisms gave significant effects for fat and protein concentration in models that also included YS. The allele substitution effects on the genetic evaluations of 670 cows daughters of two heterozygous sires were -226 kg milk, 0.09% fat, and 0.08% protein (F-value = 394), with partial dominance towards the S homozygous. We therefore propose that this YS polymorphism is the causative site for this QTL. These results clearly demonstrate the value of resequencing of genomic regions known to contain QTL. For the pig, the following research results are reported. The recent availability of the complete human genome sequence and thousands of homologous porcine sequences provides a tremendous resource for the construction of such a map of the porcine genome. Using the INRA-Minnesota porcine Radiation Hybrid (IMpRH) panel, we have constructed a radiation hybrid map composed of 2,272 markers, including 206 ESTs and 2,066 porcine BAC-end sequences (BESs). The average
spacing between comparative anchor loci is 1.15 Mb based on human genome sequence. This radiation hybrid map has the highest resolution of any porcine genome map to date, and should greatly facilitate the positional cloning of porcine genes influencing traits of economic importance. Additionally, this map will provide a framework for anchoring contigs generated through BAC fingerprinting efforts as well as assist in the selection of a BAC minimal tiling path and assembly of the first sequence-ready map of the porcine genome.
Impacts
Identification of the mutation that is responsible for lower milk yield and production traits will have a significant impact on dairy cattle improvement. A relatively simple genetic test can be used to eliminate the undesirable allele from the bull population. The development of a high resolution pig RH map consisting of more than 2,000 markers that are linked to the human genome will facilitate identification of genes controlling economically important traits for swine production.
Publications
- Cohen, M., Reichenstein, M., Everts-van der Wind, A., Lee, J.H., Shani, M., Lewin, H.A., Weller, J.I., Ron, M. and Seroussi, E. 2004. Cloning and characterization of FAM13A1: Evidence for population-wide linkage disequilibrium with a milk protein QTL on BTA6 in Israeli Holsteins. Genomics 84:374-383.
- Cohen-Zinder, M., Seroussi, E., Larkin, D.M., Loor, J.J., Everts-van der Wind, A., Lee, J.H., Drackley, J.K., Band, M.R., Shani, M., Lewin, H.A., Weller, J.I. and Ron, M. 2005. Identification of a missense mutation in the gene responsible for the QTL on BTA6 affecting milk yield and composition in dairy cattle. (Submitted).
- Humphrey, S.J., Clark, R.C., Beever, J., Scott, C.E., Plumb, B., Chardon, P., Milan, D., Archibald, A., Schook, L. and Rogers, J. 2005. Plant and Animal Genomes Conference XIII, San Diego, CA (Abstract P559).
- Lewin, H.A. 2004. The future of cattle genomics: The beef is here. Cytogenetics and Genome Research 102:10-15.
- Meyers, S. N., Rogatcheva, M.B., Yerle, M., Milan, M., Hawkins, R.J., Schook, L.B. and Beever, J.E. 2005. A high resolution, physically anchored, human-pig comparative map of the porcine autosomes. Plant and Animal Genomes Conference XIII, San Diego, CA (Abstract P558).
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