Genomic Evaluation Guidelines

DNA technology has developed rapidly in the past decade and now has a variety of applications. For beef cattle genetic improvement, the primary areas of application are pedigree validation, parentage determination, and gene-based (genotypic) selection. Individual and parentage verification are now routine practices, while gene-based selection is in the early stages of development. This chapter describes current uses of DNA technology and provides an overview of applications currently under development.

Types of DNA Markers

Analytical techniques to differentiate DNA of individuals or populations require genetic markers, which are defined as identifiable DNA segments that differ in nucleotide sequence from one individual to the next. Two types of markers may be used: microsatellites and single nucleotide polymorphisms (SNPs). Both create uniquely identifiable DNA patterns that may be used to follow the transmission of specific chromosomal regions from parents to progeny.

Microsatellite markers are segments of chromosomal DNA that include a variable number of repeated two to six nucleotide base sequences. Such markers are interspersed throughout the genome and are generally found in non-coding regions. These repetitive regions are subject to additions and subtractions in the number of tandem repeats of basic two to six nucleotide segments, and this creates uniquely identifiable alleles at each site within the genome where the particular microsatellite is found. Microsatellites routinely have been used in parentage analysis, because multiple alleles generally found at each locus make them highly informative. They have provided the basis for individual and parentage identification in humans, dogs, cattle, and many other species.

Single nucleotide polymorphisms are the type of other marker. As the name implies, they are a change (mutation) from the specific nucleotide originally present in a particular location in an individual to a different nucleotide at that same site and are transmitted from parent to offspring, just like any other gene. Across evolutionary time, thousands of SNPs have been created by mutation. They now can be found every 100 to 300 bases throughout the 3 billion base pairs in the genome. Because SNPs are widely distributed, it is likely that any gene of economic importance is located closely adjacent to several SNPs that can be used to mark its presence. SNP markers promise to be increasingly useful in the future for developing high- resolution maps because of their high throughput capability and potentially low cost. With the availability of whole genome sequences, SNPs that are dispersed across all chromosomes, present important advantages as markers for genome analysis. Some SNPs are located within the coding region of a gene and can affect the structure and function of a protein. This type of variation may be directly responsible for differences among individuals in phenotypic merit for economically important traits. Other SNPs occur either “upstream” or “downstream” of the coding region of a gene and may influence the regulation of gene expression. Others occur in locations that do not interfere with the structure or production of a protein. SNPs have the advantage that they are less likely to undergo spontaneous mutation than microsatellites; thus they are inherited with greater stability.

DNA Collection

DNA is found in every nucleated cell in the body. It can be extracted from semen, muscle, fat, white blood cells found in blood and milk, skin, and epithelial cells collected from saliva. Minute amounts of tissue, such as a single drop of blood or several mucosal cells, are all that are required for routine DNA analysis. Common collection methods include a drop of blood blotted on a paper that is dried, covered, and stored at room temperature, ear tag systems that deposit a tissue sample in an enclosed container with bar code identification, and hair follicles. Techniques have been developed that allow for rapid release of DNA from cells and immediate analysis of the samples.

Combining Molecular and Quantitative Approaches in Genetic Evaluation

Research into the molecular basis of inheritance is progressing at a rapid pace. Technologies that permit identification of molecular genetic differences in deoxyribonucleic acid (DNA) sequence among animals are also evolving very rapidly. Several DNA-based tools are being marketed in the beef industry; some as selection tools. These tools are known by a variety of names in the academic community and within the beef industry (e.g., genomic tests, DNA markers, molecular tests or markers). DNA-based selection tools present opportunities and challenges to the U.S. beef industry. Accurate DNA-based selection tools will give beef cattle breeders opportunity to identify animals with superior breeding value (BV) as soon as a tissue sample can be collected and analyzed, potentially leading to significant savings in time and money associated with performance testing and genetic evaluation. However, as currently marketed, the BV information provided by DNA-based tools is not uniformly reported and the proportion of variation in true BV accounted for by the tools is unknown. Further, the BV information provided by competing DNA-based tools overlaps and is not independent of information provided by current national cattle evaluation (NCE) systems. Performance testing and genetic evaluation are being conducted on an increasing number of traits. Types of information available (i.e., available from a practical and economical view) vary among traits. Types of information include pedigree relationships, performance measurements (i.e., phenotypes), and DNA test results. Phenotypes may include direct and indirect measurements on the same trait. Table 1 illustrates various combinations. Because most animals marketed in the U.S. as seedstock have known parentage the table assumes that pedigree relationships are known. Some traits are difficult to measure for which there are no DNA tests available. These traits will likely be the focus of future research. In a second category are traits for which phenotypes are regularly measured in the field, systematically data-based, and for which EPDs are computed. The emergence of DNA tests now permits estimation of BV on animals for which little or no phenotypic information is available (a third category). A current example would be tenderness. Tenderness phenotypes are difficult and expensive to measure, but DNA tests are available. In a fourth category are traits where both phenotypes and DNA tests are available. A current example would be carcass marbling Table 1. Traits categorized according to information available. Industry-collected Phenotypes DNA Tests No Yes No Yes --- EPD EPD EPD 1 Prepared by M. W. Tess and the BIF Commission on DNA Markers. Commission members: Bill Bowman, Ronnie Green, Ronnie Silcox, Darrell Wilkes, and Jim Wilton.

Guiding Philosophy

BIF believes that information from DNA tests only has value in selection when incorporated with all other available forms of performance information for economically important traits in NCE, and when communicated in the form of an EPD with corresponding BIF accuracy. For some economically important traits information other than DNA tests may not be available. Selection tools based on these tests should still be expressed as EPD within the normal parameters of NCE.