Genomic Prediction for Twin Pregnancies

Simple Summary Twinning in dairy cattle is caused by many different factors, both genetic (i.e., inherited) and non-genetic (i.e., animal management). In dairy operations, twinning is an undesirable trait associated with other reproductive and metabolic diseases, higher operational costs, and higher rates of culling on farm. The animal welfare and economic impacts have resulted in the development of a genomic prediction for twinning (i.e., TWIN) by Zoetis such that producers can make informed breeding decisions for breeding Holstein females that are less likely to become pregnant with twins in a given lactation. This prediction is included in a holistic breeding tool (i.e., selection index) for producers so that they can improve multiple health, fertility, and production traits in parallel with reducing twinning when making breeding decisions for future generations. The objectives of the present study were (1) to describe how the twinning prediction was developed (and included in a selection index), (2) show that the prediction works effectively using real life farm data, and (3) propose how this genetic tool can be used in collaboration with management practices to proactively reduce twin pregnancies on farm. The results of this study provide evidence that twinning can be proactively managed on dairy farms using genetically powered tools. Abstract Twinning is a multifactorial trait influenced by both genetic and environmental factors that can negatively impact animal welfare and economic sustainability on commercial dairy operations. To date, using genetic selection as a tool for reducing twinning rates on commercial dairies has been proposed, but not yet implemented. In response to this market need, Zoetis (Kalamazoo, MI, USA) has developed a genomic prediction for twin pregnancies, and included it in a comprehensive multitrait selection index. The objectives of this study were to (1) describe a genetic evaluation for twinning in Holstein cattle, (2) demonstrate the efficacy of the predictions, (3) propose strategies to reduce twin pregnancies using this information. Data were retrieved from commercial dairies and provided directly by producers upon obtaining their permission. The twin pregnancies trait (TWIN) was defined as a pregnancy resulting in birth or abortion of twin calves, classified as a binary (0,1) event, and analysed using a threshold animal model. Predictions for a subset of cows were compared to their on-farm twin records. The heritability for twin pregnancies was 0.088, and genomic predicted transmitting abilities ((g)PTAs) ranged from −7.45–20.79. Genetic correlations between TWIN and other traits were low, meaning that improvement for TWIN will not negatively impact improvement for other traits. TWIN was effectively demonstrated to identify cows most and least likely to experience a twin pregnancy in a given lactation, regardless of reproductive protocol used. Effective inclusion of the prediction in a multitrait selection index offers producers a comprehensive tool to inform selection and management decisions. When combined with sound management practices, this presents a compelling opportunity for dairy producers to proactively reduce the incidence of twin pregnancies on commercial dairy operations.


Introduction
Selection indexes are a critical component of many breeding programs and provide a way to combine information about many traits into a single number that producers can use to rank animals and inform breeding decisions. 1 The purpose of a selection index is to predict an animal's genetic potential for total economic merit. 2 Historically, selection indexes throughout the world have focused on improving production traits. 3 However, this narrow selection goal contributed to a decrease in health and fertility. 4 Improvement of phenotype recording and development of new trait evaluations led to fertility, 5 longevity, 6 milk quality, 7 and health traits 8 becoming available to breeders. Over the last 25 years, incorporation of these nonproduction traits in selection indexes has grown 9 as breeders strive to account for both incomes and expenses of an animal.
Selection indexes such as Dairy Wellness Profit Index (DWP$), Wellness Trait Index® (WT$®), and Calf Wellness Index™ (CW$™) are key components of the CLARIFIDE Plus genomic test offering. Dairy producers may seek to improve their herds by genomic testing heifers and ranking them based upon DWP$ to inform culling and breeding decisions. The dairy industry benefits from genomic technology as it results in faster genetic progress. 10,11 As the rate of genetic progress is increased, it becomes more important that DWP$ is correctly formulated and includes key economically important traits for the goal of lifetime profit. Dairy producers are leveraging genomic technology to increase selection intensity on their females through culling decisions very early in life and advanced reproductive technologies. With this combination of technologies and strategies, the costs for having a non-optimal selection index could be substantial.
As new traits become available, their influence on lifetime profitability is assessed and added to DWP$ when appropriate. Therefore, Zoetis updated DWP$ in April 2020 to incorporate new traits and update the economic values of traits previously in DWP$.

Dairy Wellness Profit Index Updates
Dairy Wellness Profit Index is a multitrait selection index that includes cow and calf wellness, production, fertility, functional type, longevity, livability, calving ability, and milk quality traits plus polled test results. Developed in 2016 by Zoetis Genetics and updated in 2018, DWP$ estimates the potential lifetime profit an animal will contribute to the dairy operation. DWP$ is expressed in a dollar value with higher positive numbers indicating the animal has the genetic potential to generate and transmit more profit over her lifetime.
In the Dairy Wellness Profit Index 2020 update, numerous changes are being implemented: • New traits that impact lifetime profitability including cow abortion, twinning, cow respiratory disease, and cystic ovaries and are included in the 2020 formulation of DWP$.
• As additional traits that impact the cow's ability to stay in the herd have become available, these traits are directly accounting for the impact of fertility and disease upon longevity. This is resulting in the economic value of productive life decreasing.

• Feet & Leg Composite and Udder
Composite, both indirect predictors of Productive Life that are measured in first lactation, have been removed from DWP$ 2020. The lifetime validation study demonstrated that Feet & Leg Composite and Udder Composite did not improve the index; this may be due to both the continued genetic progress for confirmation and the inclusion of the Zoetis wellness traits.
• The economic values of fat and protein have increased. This was done to ensure that the economic values used to develop DWP$ are representative of current and future prices dairy farmers may experience.
• The negative economic value placed upon body weight composite has changed to better represent the feed cost of larger dairy cows.
As a result, the 2020 formulation of DWP$ describes more genetic variation compared to the 2018 version as documented by the large standard deviation (254 vs 242DWP). By including more traits affecting profitability, DWP$ 2020 describes more genetic variation in profit than DWP$ 2018.
To further understand the impact of these updates to DWP$, a side by side comparison of the emphasis placed upon each trait in DWP$ 2020 and DWP$ 2018 is available in Table 1.
The following charts show the amount of emphasis each general category included in DWP$ 2020 and DWP$ 2018.
To assess how the use of DWP$ 2020 would alter genetic progress of underlying traits when compared to DWP$ 2018, the expected response to selection per standard deviation of genetic improvement of the index was estimated. In examining the response of selection between DWP$ 2020 and DWP$ 2018, use of DWP$ 2020 will result in genetic improvement in abortion, twinning, cystic ovary, and cow respiratory. DWP$ 2020 has stronger selection against body size composite resulting in selection for a more moderate sized cow. DWP$ 2020 will maintain a similar selection response for the rest of the traits in DWP$ ( Table 2).

Association Between DWP$® Predictions and Lifetime Performance
As some of the first heifers tested by Zoetis are now finishing their careers, we are now able to examine how well DWP$ predicted lifetime profit. In order to determine if DWP$ 2020 improves the capability to predict lifetime profitability better than DWP$ 2018 a side by side comparison was conducted. 13 Five large herds (n=2,175 enrolled cows) in the United States were chosen for this study because they had: (1) genomic predictions from females born in 2011, (2) recorded production, reproduction and health events to accurately estimate profit per cow (3) at least 200 animals born in 2011.

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Zoetis Lameness 5 6 Zoetis Calf Respiratory 2 2 Zoetis Calf Scours 2 2 Zoetis Calf Livability 2 4 Zoetis Cow Respiratory  Herd records were used to calculate lifetime energy corrected milk (ECM) and income over feed cost based on the actual performance from first freshening through when they left the herd; for cows that were still in the herd, current totals were used. Table 3 shows that when ranked by DWP$ 2020, the best 25% of females produced 21,460 pounds more lifetime ECM per cow than the worst 25%. This additional lifetime ECM represents $1,428 additional Income Over Feed Cost (IOFC) per cow in the best 25% of females than the worst 25%. Table 4 shows that when ranked by DWP$ 2018, the best 25% of females produced 20,018 pounds more lifetime ECM per cow than the worst 25%. This additional lifetime ECM represents $1,287 additional Income Over Feed Cost (IOFC) per cow in the best 25% of females than the worst 25%. The larger difference in lifetime ECM and lifetime IOFC between the best and worst DWP$ groups when ranked by DWP$ 2020 indicates that DWP$ 2020 has improved the ability to predict potential lifetime profitability when compared with DWP$ 2018. The updates and the incorporation of the new fertility and wellness traits to DWP$ 2020 are increasing DWP$'s ability to predict potential lifetime profitability.
Use of DWP$ under real-world conditions confirms the value of DWP$ in helping to coordinate selection toward greater profitability. The 2020 update to DWP$ can assist dairy producers in their goal to improve overall lifetime profitability of their dairy herd. 12

Wellness Trait Index Update
To support selection for reduced risk of disease in dairy females, Zoetis updated the Wellness Trait Index® (WT$®). The 2020 update to WT$ is the inclusion of cow respiratory disease while continuing to include mastitis, lameness, metritis, retained placenta, displaced abomasum, and ketosis plus polled test results. The WT$ index directly estimates potential profit contribution of the wellness traits for an individual animal. By including more wellness traits that affect profitability, WT$ 2020 describes more genetic variation in profit with a standard deviation of 108WT$.

Summary
The 2020 updates to Dairy Wellness Profit and the Wellness Trait index provide an opportunity for dairy producers to continue to select for overall herd profitability. The side by side comparison of DWP$ 2020 and DWP$ 2018 demonstrate the ability of DWP$ predictions to predict lifetime profit of Holstein animals. These results indicate that DWP$ 2020 predictions for young calves can be used to predict potential lifetime profitability. Dairy Wellness Profit predictions are a useful tool for dairy producers interested in using genetics as a method to improve their overall herd profitability. Incorporating DWP$ 2020 into breeding and culling decisions will help dairy producers create future generations of animals that have the capability for higher lifetime profit when combined with best management practices.