Source: CORNELL UNIVERSITY submitted to NRP
GENETICS OF REPRODUCTION: OVULATION AND UTERINE DISEASE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0221811
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Oct 1, 2009
Project End Date
Sep 30, 2012
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
CORNELL UNIVERSITY
(N/A)
ITHACA,NY 14853
Performing Department
Veterinarian Clinical Sciences
Non Technical Summary
Dairy cow reproductive performance has declined steadily for several decades. Genetics of reproduction has been largely ignored until recently. Much research indicates that cows ovulating early postpartum have improved reproductive performance. Recent studies suggest that time to first postpartum ovulation is more highly heritable than most reproductive traits. This provides an opportunity to identify DNA markers for early ovulation which would be useful in selection of bulls and cows for dairy production. Similarly, we have preliminary evidence to suggest that uterine disease may occur more frequently in daughters of some sires than others. Therefore we plan to identify DNA markers that are associated with susceptibility or resistance to uterine disease.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3033410102010%
3033410108030%
3043410102010%
3043410108010%
3053410102010%
3053410108010%
3113410102010%
3113410108010%
Goals / Objectives
The overall goal of this project is to identify genetic markers that identify cows most likely to ovulate soon after parturition. We also aim to identify markers associated with susceptibility to postpartum uterine disease. This information will augment genetic progress in dairy cows and help improve reproductive performance. Improved reproduction in turn contributes to sustainability of dairy production and diminished environmental impact, while enhancing profitability of food production in accordance with published CUAES research and extension priorities (http://hosts.cce.cornell.edu/admin/pwt/fy08priorities.htm).
Project Methods
Our overall objective is to identify genetic markers for early ovulation and for susceptibility (or resistance) to postpartum uterine disease. We will do this by genome-wide association studies, using the newly available bovine SNP chip from Illumina. We will examine two populations: the first is a well-characterized group of cows for which we have daily energy balance for 30 days pre and post partum, periparturient profile sof several metabolites and hormones (including LH), daily ultrasound examinations, and day of ovulation. (These data are in hand and DNA has been banked.) The second population consistes of large groups of half-sibs on a commercial dairy farm. Approximately 200 daughters of each of five bulls will be characterized for uterine health and time to first postpartum ovulation by regular examination and milk progesterone assay. Whole-genome association studies will be performed to identify informative SNPs for early ovulation and susceptibility / resistance to uterine disease. DNA from these cows will be used for genotyping using the Bovine SNP%) bead chip from Illumina at the Cornell University Life Sciences Core laboratory Center, This chip contains 54,000 evenly distributed polymorphic SNPs with a mean gap of 51.5 kb and representing an average minor allele frequency of 0.25 across all loci. Current research on linkage disequilibrium (LD) in cattle suggests haplotype blocks of approximately 70 kb on average (Khatkar et al., 2007), indicating that the resolution offered by the Bovine SNP50 chip is well within the resolution of LD in cattle. Analysis will be performed for association of SNPs with phenotype (early ovulation, resistance to uterine disease) of interest. A regression approach will be used to allow inclusion of fixed effects and co-variates including the energy status, calf status, insulin resistance status and other known factors that could influence ovulation or uterine disease resistance. We believe this project is highly likely to succeed. All the procedures are in place in laboratories of the investigators, or in the Cornell Life Sciences Core laboratory Center. In addition, the presence of many colleagues with skills in this area of science suggests that we will be able to obtain any necessary assistance or advice on the campus. The experiment for the second objective is large, and the available funding will not allow its completion. Objective 1 will be fully completed. All sampling for Objective 2 will be completed. SNP analysis of selected samples will be possible for Objective 2. Completion of Objective 2 will require additional funding. Conversations are in progress with potential corporate sponsors with an interest in this experiment, and we are confident that we will identify the resources necessary for completion of this experiment and progression to QTL identification and ultimately, to identification of specific genes.

Progress 10/01/09 to 09/30/12

Outputs
OUTPUTS: Findings of this study have been incorporated into lectures in dairy cattle reproduction to veterinary professional students. A visiting lecture was delivered at Cambridge University, UK, during May 2011. Findings have also been disseminated at extension meetings in Florida, by a former student. Work was included in the graduate work of Dr. S.H. Cheong and incorporated into his PhD defense seminar at Cornell University, and at seminars given at the University of Illinois. Results of this project have been included in presentations to veterinarians in Argentina (2010), Italy (2010), Uruguay (2010), Brazil (2010) and Canada (2010) by Dr. Gilbert. Results of this research were incorporated into presentations to veterinarians registered for PhD degrees in reproduction at a course given jointly by the University of Tartu and the Estonian University of Life Sciences in May, 2010; 22 veterinarians from Scandinavia and Eastern Europe attended. Results were incorporated into presentations for veterinarians in China 2010, 2011 and 2012. PARTICIPANTS: Dr. R.O. Gilbert: PI Dr. W.R. Butler: Co-PI Trainees: Dr. S.H. Cheong (PhD) Dr. O. Balogh (PhD) Dr. K.N. Galvao Collaborating institutions: University of Florida St. Istvan University, Hungary. TARGET AUDIENCES: Academic veterinarians and animal scientists. Practicing veterinarians and animal scientists involved in the dairy industry. Veterinary professional students. Dairy producers. Dairy geneticists and animal breeding organizations. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The major findings of this project are as follows: 1. Cows ovulating before 21 days postpartum have superior reproductive performance to cows ovulating for the first time between 21 and 49 days postpartum, which, in turn, have better reproductive performance than those whose first ovulation occurs later than 49 days postpartum. 2. Cows ovulating earlier in the postpartum period are less likely to suffer from endometritis. 3. The detrimental effects of late ovulation and endometritis on reproductive performance are independent, and additive. 4. Cows failing to ovulate the first postpartum dominant follicle have lower dry matter intake starting at least 30 days prepartum, have more severe negative energy balance, and greater insulin resistance than cows ovulating the first dominant follicle. 5. Although cows ovulating the first postpartum dominant follicle have higher circulating concentrations of anti-Muellerian hormone (AMH; a measure of antral follicular count, or ovarian reserve) than non-ovulating cows, this effect is weak, and the high antral follicle count and early postpartum ovulation seem to be independent characteristics. 6. Preliminary results of a Genome-wide Association Study indicate that most significant hits so far are on chromosome 15 (SAAL1 - serum amyloid A like-1) and chromosome 4(HIBADH -- 3-hydroxyisobutyrate dehydrogenase; TAX1BP1 - tax-1 binding protein-1). Both genes play a role in signaling cascades related to inflammation. 7. In other results we have established a role for the GH-IGF-1 axis. These results were made possible by the activities of the personnel involved in this project. These results provide justification for enrollment of a greater number of cows into a genome-wide association study, with a high likelihood of discovering genetic markers to aid selection for fertility, and identification of genes that will enhance our understanding of fertility of dairy cows.

Publications

  • Balogh O, Kovacs K, Kulcar M, Gaspardy A, Febel H, Zsolnai A, Fesus L, Delavaud C, Chilliard Y, Gilbert RO, Huszenicza Gy. Interrelationship of growth hormone ALUI polymorphism and hyperketonemia with plasma hormones and metabolites in the beginning of lactation in dairy cows. Livestock Science. 2009; 123: 180-186.
  • Galvao KN, Butler WR, Brittin SB, Frajblat M, Guard CL, Gilbert RO. Effect of early postpartum ovulation on fertility in dairy cows. Reproduction in Domestic Animals. 2010 45, e207-e211 (2010)
  • Galvao KN, Pighetti GM, Cheong SH, Nydam DV, Gilbert RO. Association between CXCR1 polymorphism and disease incidence, reproductive performance and milk production in Holstein cows. Journal of Dairy Science. 2011; 94: 2083-2091
  • Gilbert RO. The effects of endometritis on the establishment of pregnancy in cattle. Reproduction, Fertility and Development. 2012; 24: 252-257. doi: 10.1071/RD11915; PMID: 22394966


Progress 10/01/10 to 09/30/11

Outputs
OUTPUTS: Dissemination of data during the reporting period has included incorporation of new information in lectures on dairy cow reproduction for veterinary students, both at Cornell University and the University of Cambridge. PARTICIPANTS: This project has supported part of the work upon which the PhD project of Dr. S.H. Cheong is based. TARGET AUDIENCES: The target audiences include veterinarians and veterinary students, professional animal scientists and animal science students, the animal breeding industry and dairy producers. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Preliminary results have indicated that genes located on chromosomes 15 and 4 are likely to be associated with likelihood of ovulation of the first postpartum dominant follicle. These findings will be consolidated with examination of additional animals in the current year. Identification of specific genes and polymorphisms associated with early postpartum ovulation will allow specific selection of animals likely to ovulate early in the postpartum period, with the attendant health and reproduction benefits.

Publications

  • Galvao KN, Pighetti GM, Cheong SH, Nydam DV, Gilbert RO. 2011. Association between CXCR1 polymorphism and disease incidence, reproductive performance and milk production in Holstein cows. J.Dairy Sci. 94:2083-2091.


Progress 10/01/09 to 09/30/10

Outputs
OUTPUTS: This being the first year of the project, much of the dissemination of information was limited to our preliminary data and findings upon which the application was based although some new information was discovered and disseminated. Information obtained to date in this project has been shared in a variety of ways. These include incorporation of current findings in lectures to veterinary students taking an advanced dairy cattle reproduction course. Material was also included in lectures to veterinarians and veterinary students participating in the Summer Dairy Institute at Cornell in 2010. In addition, presentations were made to graduate students at several universities worldwide, including: University of Saskatchewan, College of Veterinary Medicine, March 2010; State University of Sao Paulo, Brazil, College of Veterinary Medicine, 2010; University of the Republic of Uruguay (Universidad de la Republica), College of Veterinary Medicine, April, 2010; University of Tartu and Estonian University of Life Sciences, Estonia, May 23 - 28, 2010; and the Faculty of Veterinary Science, Universidad Nacional del Centro, Tandil, Buenos Aires, Argentina, July 2010. Some data were also presented at a meeting of Veterinarians in dairy practice in Italy: SIVAR (Societa Italiana Veterinari per Animali da Reddito) Congress, Cremona Italy, May 6-8, 2010. Most of these audiences consisted of veterinarians or veterinary students. In many cases, proceedings were published, often in local languages, further facilitating dissemination of the information. The data and concepts of this study were discussed at the annual technical meeting of the National Association of Animal Breeders (NAAB) in Milwaukee, Wisconsin in September 2010. This audience consists of management of bull studs from around North America as well as leading reproductive scientists. At this meeting, officials of the NAAB also agreed to share some bull genomic information to facilitate our study and prevent duplication. Discussion of the goals and activities of this project in Uruguay have led to inauguration of a new collaborative effort to advance progress in this field. The animals in Uruguay are mainly of US genetics, so the information obtained there will be applicable in the USA. PARTICIPANTS: Project Director: Dr. R.O. Gilbert Co-Investigator: Dr. W.R. Butler Dr. Marcela Bicalho: postdoctoral associate Graduate Students: Dr. Klibs Galvao: Completed PhD and now Assistant Professor, University of Florida. Dr. Soon Hon Cheong: Current PhD student, Cornell University Collaborators: Dr. Gina Pighetti, University of Tennessee Dr. Ana Meikle, University of Uruguay Dr. Daniel Cavestany, University of Uruguay TARGET AUDIENCES: During the reporting year, veterinary students and veterinarians were targeted in presentations at Cornell University, the University of Saskatchewan, the University of Sao Paulo, the University of Tandil, Argentina, the University of Uruguay, the University of Tartu and the Estonian University of Life Sciences, Estonia. A non-veterinary audience was targeted at the annual meeting of the National Association of Animal Breeders. A greater awareness of the importance of genetics in dairy cattle reproduction is likely to be multiplied in their interactions with their producer-clients. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
For several decades genetics have been overlooked as a potential contributor to steadily deteriorating reproductive performance in high producing dairy cows. Our interest in this subject and our preliminary findings, along with those of others, have rekindled interest in a genetic approach to enhanced reproductive performance. The result is that reproductive traits are now given more prominence in many national and international breeding / selection indices. Although we cannot claim to have brought this about, we do feel we have contributed to this movement. Investigation of specific candidate genes suspected to have an impact on dairy cow reproduction has had mixed results. We have been able to confirm a lack of effect of mutations in the CXCR2 gene, and the ALU1 gene. On the other hand, we have obtained very encouraging data related to GHR polymorphism. Although we will continue to investigate candidate genes in an effort to understand the relevant biology, we have turned our attention for now to genome-wide association studies in the hope of identifying areas of linkage disequilibrium, which in turn will lead to more promising candidate genes and processes. In collecting samples and characterizing performance (phenotype) of dairy cows for this project, we have reinforced the importance of the relationship between energy status, uterine health, and ovarian function. Genes common to these processes seem likely to provide selection markers and we will continue to investigate them.

Publications

  • Galvao KN, Butler WR, Brittin SB, Frajblat M, Guard CL, Gilbert RO. 2010. Effect of early postpartum ovulation on fertility in dairy cows. Reproduction in Domestic Animals. 45, e207 -e211 (2010); doi: 10.1111/j.1439-0531.2009.01517.x ISSN 0936-676
  • Balogh O, Kovacs K, Kulcar M, Gaspardy A, Febel H, Zsolnai A, Fesus L, Delavaud C, Chilliard Y, Gilbert RO, Huszenicza Gy. 2009. Interrelationship of growth hormone ALUI polymorphism and hyperketonemia with plasma hormones and metabolites in the beginning of lactation in dairy cows. Livestock Science. 123: 180-186.