Progress 07/01/07 to 06/30/12
Outputs
OUTPUTS: The objectives of my research are to identify and characterize genes and pathways for embryo development, quality, and viability in humans and cattle. This year our results have disseminated to the scientific community by several publications in different journals. PARTICIPANTS: Hasan Khatib, PI; Wen Huang, graduate student; Ashley Driver, graduate student; Bao Zhang, visiting scholar; Geng li, visiting scholar; Asif Nadeem, visiting scholar TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The IVF system developed in our lab is the first system in any mammalian species designed to identify genes affecting fertility traits. The outcomes of these study could lead to solving one of the most urgent problems in the dairy industry, which is the decrease in cow fertility observed for the last 40-50 years.
Publications
- Huang, W., Kirkpatrick BW, Rosa GJM, and Khatib H. 2010. A genome wide association study using selective DNA pooling identifies candidate markers for fertility in Holstein cattle. Anim Genet. 41:570-8.
- Huang W, Khatib H. 2010. Comparison of transcriptomic landscapes of bovine embryos using RNA-Seq. BMC Genomics 11:711.
- Khatib H, Monson RL, Huang W, Khatib R, Schutzkus V, Khateeb V, Parrish JJ. 2010. Validation of In-vitro Fertility Genes in a Holstein Bull Population. J. Dairy Sci. 93:2244-9.
- Zaitoun I, Downs KM, Rosa GJM, Khatib H. 2010. Upregulation of Imprinted Genes in Mouse. Epigenetics 5:149 - 158.
- Huang W, Yandell BS, Khatib H. 2010. Transcriptomic Profiling of Bovine IVF Embryos Revealed Candidate Genes and Pathways Involved in Early Embryonic Death. BMC Genomics 11:23.
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: The decrease in fertility in dairy cattle is a worldwide problem. In the U.S.A., the conception rate for cattle at first artificial insemination has been decreasing for many years with an estimated decrease of 0.45% per year over a 20-year period. The first-service conception rate declined from ~65% in 1951 to ~40% in 1996. In the UK, the conception rate is declining at about 1% per year, and at first-service it is currently lower than 40%. Similar trends of declining fertility in dairy cows have also been observed in France, Ireland, Netherlands, and Canada. The reasons for this reduced reproductive efficiency are manifold, but it seems likely that there is a genetic basis for some of this infertility and thus genetic manipulation may also continue to attenuate this problem. In order to identify genes affecting fertility traits, we have established an in-vitro fertilization system in cattle. In this system, we study the association between fertilization rate and embryonic survival rate with our candidate genes. PARTICIPANTS: Wen Hunag; Xin Wang; Val Schutzkus; Undergraduate students; Guilherme Rosa (collaborator); Ricky Monson (Collaborator); Merial Igenity (support for some of the projects) TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The IVF system developed in our lab is the first system in any mammalian species designed to identify genes affecting fertility traits. Indeed, several genes were found to be associated with fertilization and early embryonic survival. These two traits mimic natural pregnancy in cows. The preliminary data obtained in our lab for few genes has prompted us to carry out whole genome scan in order to screen all genes in the cattle genome for fertility effects. Also, we have established collaborations with the dairy industry in order to validate our in-vitro results in live animals. The outcomes of these study could lead to solving one of the most urgent problems in the dairy industry, which is the decrease in cow fertility observed for the last 40-50 years.
Publications
- Huang W, Mikheil D, Bindrin A, Khatib H. 2009. A SNP in bovine placental lactogen and its interactions with hormone receptors are associated with fertility traits in cattle. Animal 3: 1743-1745.
- Wang X, Schutzkus V, Huang W, Rosa GJM, and Khatib H. 2009. Analysis of segregation distortion and association of the bovine FGF2 with fertilization rate and early embryonic survival. Animal Genetics 40: 722-728.
- Driver AM, Huang W, Gajic S, Monson RL, Rosa GJM, Khatib H. 2009. Effects of the Progesterone Receptor Variants on Fertility Traits in Cattle. J Dairy Sci. 92(8):4082-4085.
- Khatib H, Huang W, Wang X, Tran AH, Bindrim AB, Schutzkus V, Monson RL, Yandell BS. 2009. Single Gene and Gene Interaction Effects on Fertilization and Embryonic Survival Rates in Cattle. J Dairy Sci. 92, 2238-2247.
- Khatib H, Maltecca C, Monson RL, Schutzkus V, and Rutledge JJ. 2009. Monoallelic maternal expression of STAT5A affects embryonic survival in cattle. BMC Genetics 10:13.
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: My research program is focused on two major fields. The first is applied research on candidate genes affecting production and reproduction traits in cattle. The second is basic research on the mechanisms leading to differential expression of monoallelically- versus biallelically-expressed genes, including imprinted genes. Currently, candidate genes are chosen based on the results of previous linkage mapping studies and on comparative biological or physiological functions in other species. However, one major limitation when choosing candidate genes with this approach is the large number of provisional genes typically present in quantitative trait loci (QTL) regions. Another limitation is the lack of consistency between position and function of some candidate genes.Thus, we have developed a new approach in which candidate genes are chosen based on their biological functions in metabolic pathways. PARTICIPANTS: Hasan Khatib,Val Schuzkus, Wen Huang,Chris Maltecca, Ricky Monson,Jack Rutledge, and Guilherme Rosa TARGET AUDIENCES: Dairy cattle breeding associations, dairy producers and farmers in Wisconsin and in the US. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Our approach was the first to identify genes affecting milk production and fertility traits based on their biological functions. The resources of the USDA (PROVIDED POPULATION OF BULLS)and those of our department (Dr. George Shook (provided a cow population for testing) have helped much with achieving our objectives. Indeed, there is a great interest in our genes by the dairy industry. Also, as a recognition of the methodology and achievements, the PI was invited by the Chinese government to give presentations and discuss collaborations with Chinese Universities. Several publications have resulted from this project (see publication section).
Publications
- Maltecca C, Weigel K A, Khatib H, Cowan M and Bagnato A. 2008. Whole Genome Search for quantitative trait loci associated with birth weight, gestation length and passive immune transfer in a Holstein Jersey crossbred population. Animal Genetics. In press
- Huang W, Maltecca C, Khatib H. 2008. A proline to histidine mutation in POU1F1 is associated with production traits in dairy cattle.Animal Genetics 39:554-557.
- Khatib H and Kim E. 2008. The distribution and conservation of retrotransposable elements in cattle. Epigenetics 3(2).
- Wang X, Maltecca C, Tal-Stein R, Lipkin E, Khatib H. 2008. Association of bovine fibroblast growth factor 2 (FGF2) gene with milk fat and productive life: an example of the ability of the candidate pathway strategy to identify quantitative trait genes. J Dairy Sci. 91(6):2475-80.
- Khatib H, Maltecca C, Monson RL, Schutzkus V, Wang X, Rutledge JJ. 2008. The fibroblast growth factor 2 gene is associated with embryonic mortality in cattle. J Anim Sci. 86(9):2063-7.
- Khatib H, Monson RL, Schutzkus V, Kohl DM, Rosa GJ, Rutledge JJ. 2008. Mutations in the STAT5A gene are associated with embryonic survival and milk composition in cattle. J Dairy Sci. 91(2):784-93.
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: My research program is focused on two major fields. The first is applied research on candidate genes affecting production and reproduction traits in cattle. The second is basic research on the mechanisms leading to differential expression of monoallelically- versus biallelically-expressed genes, including imprinted genes. Currently, candidate genes are chosen based on the results of previous linkage mapping studies and on comparative biological or physiological functions in other species. However, one major limitation when choosing candidate genes with this approach is the large number of provisional genes typically present in quantitative trait loci (QTL) regions. Another limitation is the lack of consistency between position and function of some candidate genes.
PARTICIPANTS: Valerie Schutskuz (Lab manager)
TARGET AUDIENCES: Dairy cattle breeding associations, dairy producers and farmers in Wisconsin and in the US
Impacts
There is a need to increase the efficiency of positional cloning of quantitative trait genes (QTGs) by choosing candidate genes with a higher chance of success. Once known, QTGs can be selected for or manipulated in genetic improvement programs. My hypothesis is that candidate genes affecting quantitative traits can be identified by tracking their biological action through intracellular effector pathways. Recently, we have used this approach to identify candidate genes affecting fertility and milk production traits.
Publications
- 1. Khatib H, Schutzkus V, Chang Y M, and Rosa G J M. 2007. Pattern of Expression of the Uterine Milk Protein Gene and its Association with Productive Life in Dairy Cattle. J Dairy Sci 90, 2427-2433.
- 2. Khatib H, Zaitoun I, Wiebelhaus-Finger J, Chang Y M and Rosa G J M. 2007. The bovine PPARGC1A and OPN genes are associated with milk composition in Holstein Dairy Cattle. J Dairy Sci 90, 2966-2970.
- 3. Cobanoglu O, Zaitoun I, Chang YM, Shook GE, Khatib H. 2006. Effects of the signal transducer and activator of transcription 1 (STAT1) gene on milk production traits in Holstein dairy cattle. J Dairy Sci. 89, 4433-4437.
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