Genomics in the U.S. in a nutshell
The first U.S. dairy cattle genomic evaluation was released in April 2008. Official status was designated starting with the January 2009 evaluation. Since then, the number of animals genotyped per year has rapidly increased to an impressive figure of 500,000 animals a year (90% of which are females). CDCB certified genotyping laboratories along with breed associations and artificial-insemination (AI) organizations collect samples for DNA extraction, provide pedigree data, and notify the CDCB that they want an animal to receive a genomic evaluation (process known as Nomination). Most animals are genotyped with chips that have between 18,000 and 30,000 single-nucleotide polymorphism (SNP) markers. Higher density chips are used in research and for bulls to be marketed. The SNP genotypes in each submission are evaluated for call rate, portion heterozygous, and parent-progeny consistency.
Each animal genotype is checked against its parents and a grandparent if the parent has not been genotyped. Of the animals with genotypes that are usable for genomic evaluation, 97% had sires and 38% had dams that were genotyped. Each genotype is compared with all others to discover identical genotypes or parent-progeny relationships not in the pedigree. These checks are important to ensure that the genotype is assigned to the correct animal.
Genotypes from chips of differing SNP densities are included in the evaluation by using imputation to fill in the SNPs that are not observed. Currently, 60,671 SNPs are used in U.S. genomic evaluation of dairy cattle. Various genetic abnormalities also are tested for, and these test results are included in the imputation to provide an imputed indication of carrier status for animals that are not tested. Haplotypes that affect fertility also are used to detect reproductive defects. To date, 11 such haplotypes have been detected, and the causative variant has been discovered for 7 of those. Reliance on genomic evaluations to select bulls has increased rapidly. In 2016, 67% of breedings through AI were to bulls with no milking progeny. Evaluations of new animals are released weekly because of owner interest in making culling decisions as early as possible to minimize rearing costs. The AI organizations also rely heavily on genomic evaluations to generate the next generation of bulls. The age of parents at bull birth has dropped to just over 2 years, nearly the biological minimum. This reduction in generation interval has led to almost doubling the annual genetic improvement (over $80/year for lifetime net merit, a genetic-economic index). Research on new traits is constant, with new traits being released each year. With genomics, a new trait can be extended to the entire genotyped population as soon as an adequate reference population has been measured for the trait.
The genomic revolution has resulted in a faster change in dairy cattle breeding than any previous technology. CDCB is leading this effort of providing the best, most reliable and most accurate genomic evaluation for the whole U.S. dairy industry.
How genomic data flows into the system
Genomic data flow starts with the farmer deciding to genotype their animals. By examining the figure above, it is clear that CDCB approved Genomic Nominators role is key to this system. A genomic nominator collects the pedigree information (animal, sire and dam ids, date of birth, etc…) and determines the correct CDCB fee, following the CDCB fee schedule. This process is called Nomination. Among the duties of the nominator, there’s also the (direct or indirect) collection of biological samples and it’s forwarding to a CDCB certified Genotyping laboratory. CDCB receives nomination data from nominators and raw genomic data from genotyping laboratories. Once the data is processed, quality reports are shared to both parties. CDCB monthly reports on the quality of the data received from each genomic nominator and genotyping laboratory, in order to ensure the highest standards possible of the data stored in the CDCB collaborators’ database. Correct and validated data are then included in the genomic evaluations, following the rules of publication (see below) and the genetic evaluations release schedule.
Nomination
Nomination is one of the most important data CDCB receives from its clients. Nomination is a process where a series of critical information is included in the CDCB collaborator database:
- pedigree of the animal: important not only for the evaluation itself but also for genomic checking (parent-progeny control). There is a constant exchange of pedigrees between CDCB and national and international breed associations to ensure the databases are up to date and in synch.
- association between the genotype sample ID and the animal ID.
- fee code. Depending on the contribution of the herd to the system, each animal is assigned a fee for the service provided. Details are provided in the CDCB fee schedule.
- type of service required. Some genotypes are received for parentage checking only, some others for full evaluation service.
Genotyping
In order to ensure the best data quality possible, CDCB accepts genotypes from CDCB approved Genotyping Laboratories or from international evaluation centers. The CDCB collaborator’s database can store multiple genotypes for the same animal, as it relies in chip identification and sample location on the chip (a.k.a. barcode and barcode position). As samples are loaded to the database, they are checked on an animal basis for call rate, sex and (grand)parent-progeny conflicts. A preliminary check is provided to enable the laboratory to correct problems before submitting genotypes for loading. In addition to conflicts with reported (grand)parents, a conflict also is reported if an unexpected close relationship is found in the database. Quality of the genotypes received by the CDCB is audited on a monthly basis, based on a series of metrics defined in the CDCB Quality Certification document.
Fee Schedule
The CDCB genomic fees are structured to reward producers that are providing the most data or information for the greatest value to the CDCB cooperator database. The current fee schedule encourages contributors to not only maintain, but to increase the amount and kinds of data they are contributing to the system, to improve accurate genetic evaluations. All required Initial Fees are to be collected by the genomic nominator. The AI Service Fee is collected by NAAB. All fees collected will be then be forwarded to the CDCB. The female and initial male fees will be charged only for the first genotype submitted for genomic evaluation for the animal. There will be no refund of fees, except for errors generated by CDCB. Even if the genomic test results do not work to the submitter’s satisfaction or a male is not placed into service. The detailed information is described in here . The CDCB has also created the CDCB Fee Schedule application: a decision tree tool to help users determining the appropriate fee codes.
Genotypes and genomic evaluation
Genotypes declared “usable” (e.g. those who pass all the quality controls and have a complete nomination) are considered for genomic evaluation. The process starts with their extraction from the database. Although CDCB stores the raw genotypes, not all SNPs are extracted. Only SNPs belonging to the list of 60,671 currently used in the genomic evaluation are considered. Imputation using FindHap algorithm (VanRaden et al., 2011) is used to fill in missing genotypes.
The SNP effects on traditional evaluations are estimated for more than 30 traits. Traditional evaluations are de-regressed to make data more like individual records, as explained in Wiggans et al. (2010). Methodology to obtain SNP effects and the process to obtain a full genomic prediction is explained in VanRaden et al. (2009).
Rules of publication
Publication of animals depends on a series of characteristics. Nomination has to be successful and a fee code for the animal has to be assigned. Each animal genotype undergoes a thorough checking process to determine which genotypes are designated as “usable” and, therefore, receive a preliminary (unofficial) weekly genomic evaluation.
U.S. animals, irrespectively of their sex, and foreign females will be then published on each official monthly genomic evaluation. The only exception is for those animals that are marketed using CDCB genomic evaluations (i.e. animals with AI service fee paid): these animals are published during the tri-annual official runs.
Foreign animals are published on monthly evaluations until they reach their 16th month of age. After that, foreign animals will be published (on the triannual evaluations) if their AI service fee is paid.
Note no animal can be marketed using U.S. evaluations if not included in the NAAB cross-reference program and their AI service fee is paid (or waived).
References
- VanRaden, P.M., J.R. O’Connell, G.R. Wiggans, and K.A. Weigel (2011). Genomic evaluations with many more genotypes. Genet. Sel. Evol. 43:10.
- Wiggans, G.r., VanRaden, P.M., and T.A. Cooper (2010). The genomic evaluation system in the United States: Past, present, future. J. Dairy Sci. 94:3202-3211
- VanRaden, P.M., Van Tassell, C.P., Wiggans, G.R., Sonstegard, T.S., Schnabel, R.D., Taylor, J..F and F.S. Schenkel (2009). Invited review: reliability of genomic predictions for North American Holstein bulls. J. Dairy Sci. 92:16-24.