Difference between revisions of "Genomic Evaluation Guidelines"

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DNA technology has developed rapidly in the past decade and now has a variety of
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[[Category: Genetic Evaluation]]
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[[Category:Data Collection]]
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DNA technology has developed rapidly in the past nearly two decades and now has a variety of
 
applications. For beef cattle genetic improvement, the primary areas of application are
 
applications. For beef cattle genetic improvement, the primary areas of application are
 
pedigree validation, parentage determination, and gene-based (genotypic) selection.
 
pedigree validation, parentage determination, and gene-based (genotypic) selection.
Individual and parentage verification are now routine practices, while gene-based
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Individual and parentage verifications are now routine practices, and genomic data are now routinely used in [[Expected Progeny Difference | EPD]] production. This chapter describes the current uses of
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.
 
DNA technology and provides an overview of applications currently under development.
==Types of DNA Markers==
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==DNA Markers==
 
Analytical techniques to differentiate DNA of individuals or populations require genetic
 
Analytical techniques to differentiate DNA of individuals or populations require genetic
 
markers, which are defined as identifiable DNA segments that differ in nucleotide
 
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:
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sequence from one individual to the next. The current standard for identifying genomic markers is single nucleotide polymorphisms (SNPs). [https://www.illumina.com/science/technology/beadarray-technology.html Beadarray based "chips"] create uniquely
microsatellites and single nucleotide polymorphisms (SNPs). Both create uniquely
 
 
identifiable DNA patterns that may be used to follow the transmission of specific
 
identifiable DNA patterns that may be used to follow the transmission of specific
 
chromosomal regions from parents to progeny.
 
chromosomal regions from parents to progeny.
  
Microsatellite markers are segments of chromosomal DNA that include a variable
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As the name implies, SNPs are a change (mutation) from the specific nucleotide originally present in a
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
 
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,
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transmitted from parent to offspring, just like a gene. Across evolutionary time,
 
thousands of SNPs have been created by mutation. They now can be found every 100
 
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
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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
 
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.
 
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-
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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 in generating data.
resolution maps because of their high throughput capability and potentially low cost.
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With the availability of whole-genome sequences, SNPs that are dispersed across all
With the availability of whole genome sequences, SNPs that are dispersed across all
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chromosomes present important advantages as markers for genomic analysis.
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
 
Some SNPs are located within the coding region of a gene and can affect the structure
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Other SNPs occur either “upstream” or “downstream” of the coding region of a gene and
 
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
 
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
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interfere with the structure or production of a protein.
they are less likely to undergo spontaneous mutation than microsatellites; thus they are
 
inherited with greater stability.
 
  
 
==DNA Collection==
 
==DNA Collection==
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==Combining Molecular and Quantitative Approaches in Genetic Evaluation==
 
==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
 
Performance testing and genetic evaluation are being conducted on an increasing
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economical view) vary among traits. Types of information include pedigree
 
economical view) vary among traits. Types of information include pedigree
 
relationships, performance measurements (i.e., phenotypes), and DNA test results.
 
relationships, performance measurements (i.e., phenotypes), and DNA test results.
Phenotypes may include direct and indirect measurements on the same trait. Table 1
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Phenotypes may include direct and indirect measurements on the same trait.  
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
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Some traits are difficult to measure for which there are currently no DNA tests available. These
 
traits will likely be the focus of future research. In a second category are traits for which
 
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
 
phenotypes are regularly measured in the field, systematically data-based, and for
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current example would be tenderness. Tenderness phenotypes are difficult and
 
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
 
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 [[Marbling Score | carcass
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both phenotypes and DNA tests are available. A current example would be [[Marbling score | carcass
 
marbling]].
 
marbling]].
  
Table 1. Traits categorized according to information available.
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===Guiding Philosophy===
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.''
 
''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.''
  
==Types of Current DNA Technologies==
 
There are a variety of DNA-based tools available to the beef industry today. The
 
number of DNA-based technologies marketed will likely increase rapidly over time.
 
Following is a list of the broad types available based on their applications. All are based
 
on identifying differences in DNA base-pair sequence among animals. The number of
 
base pairs involved, and the lab techniques employed vary greatly.
 
Parentage Identification/Validation tests are used to identify or validate identification
 
of sires and dams of calves. The calf and at least one parent are tested.
 
 
'''Identification/Traceability tests'' are used to track animals and tissues through the food
 
production chain as animals and their products change ownership and move from
 
location to location. Variation in DNA is used to identify individual animals. Each animal
 
being tracked must be tested.
 
 
'''Management tests''' are used to predict the future phenotypes of animals in specific
 
production/marketing systems. They are based on identifying differences in total genetic
 
merit among animals (i.e., additive and non-additive genetic merit).
 
 
'''Selection tests''' are used to estimate breeding value (i.e., distinguish among animals on
 
the basis of their progeny performance). Traits may be qualitative or quantitative in
 
nature. Qualitative traits are controlled by one or a few loci, and phenotypes generally
 
fall into distinct classes (e.g., presence of horns, coat color, and certain genetic
 
defects). Quantitative traits are controlled by many loci. Quantitative phenotypes may be
 
measured on a continuous scale (e.g., weights) or in classes (e.g., pregnancy success).
 
''The focus of the guidelines presented here is on DNA tests for quantitative traits used
 
for selection.''
 
 
==Validation==
 
==Validation==
 
DNA tests are developed based on associations between variations in base-pair
 
DNA tests are developed based on associations between variations in base-pair
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using DNA tests for selection.
 
using DNA tests for selection.
  
''BIF recommends that breeders who use DNA-tests should, whenever possible, choose DNA-tests that have been validated in populations that are representative of the beef cattle industry by scientists independent of the organization that developed or will market the test.''
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''BIF recommends that breeders who use DNA tests should, whenever possible, choose DNA tests that have been validated in populations that are representative of the beef cattle industry by scientists independent of the organization that developed or will market the test.''
  
 
==Assessment==
 
==Assessment==
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DNA tests overlap and how non-target traits will be influenced by selection based on
 
DNA tests overlap and how non-target traits will be influenced by selection based on
 
these tests. For example, it is important to know if selection based on a DNA test for
 
these tests. For example, it is important to know if selection based on a DNA test for
[[Shear Force | tenderness]] has any desirable or adverse effects on other economically important traits
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[[Measures of Tenderness | tenderness]] has any desirable or adverse effects on other economically important traits
 
(growth, feed intake, fertility, etc.). As with validation, assessment studies are
 
(growth, feed intake, fertility, etc.). As with validation, assessment studies are
 
considered to be more reliable if conducted by scientists who have no vested interest in
 
considered to be more reliable if conducted by scientists who have no vested interest in
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''BIF recommends that assessment studies should be conducted in populations that are representative of the beef cattle industry by scientists independent of the organization that developed or will market the test.''
 
''BIF recommends that assessment studies should be conducted in populations that are representative of the beef cattle industry by scientists independent of the organization that developed or will market the test.''
 
==Reference Populations==
 
As used here, reference populations are: 1) pedigreed herds that are representative of
 
and genetically linked to commercial populations in the beef industry, 2) managed in
 
production/marketing systems representative of the beef industry, 3) measured for
 
economically relevant traits and (or) important indicator traits, and 4) from which tissue
 
samples are available.
 
 
Ownership may be public or private; however, as envisioned here the most useful on-
 
going reference populations are likely to be federally owned and managed.
 
BIF recognizes the critical importance of pedigreed reference populations for the
 
successful implementation of DNA-based selection tools in the beef industry. BIF
 
considers the partnerships of USDA-ARS and Agriculture Canada in the establishment
 
and maintenance of reference populations to be vital to the successful implementation
 
of DNA-based selection tools in the beef industry.
 
  
 
==Inclusion of DNA Test Information in NCE Programs==
 
==Inclusion of DNA Test Information in NCE Programs==
 
Statistical procedures for incorporating DNA test information into NCE and the
 
Statistical procedures for incorporating DNA test information into NCE and the
computation of EPD and associated accuracies is described in [[Single-step Hybrid Marker Effects Models]] and [[Single-step Genomic BLUP]]. Results of the evaluation of a DNA test will also provide estimated genetic correlations
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computation of EPD and associated accuracies are described in [[Single-step Hybrid Marker Effects Models]] and [[Single-step Genomic BLUP]]. Results of the evaluation of a DNA test will also provide estimated genetic correlations
 
among competing DNA tests, genetic correlations between DNA tests and non-target
 
among competing DNA tests, genetic correlations between DNA tests and non-target
 
traits, and the fraction of the additive genetic variance of the target trait accounted for by
 
traits, and the fraction of the additive genetic variance of the target trait accounted for by
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and increase in accuracy provided by the addition of the DNA test information.
 
and increase in accuracy provided by the addition of the DNA test information.
 
BIF recommends that a DNA test should be considered for inclusion in the NCE system
 
BIF recommends that a DNA test should be considered for inclusion in the NCE system
when after estimating the covariances and running the NCE system, use of the DNA
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when, after estimating the covariances and running the NCE system, use of the DNA
 
test results in more accurate EPD at a young age.
 
test results in more accurate EPD at a young age.
  
 
Reporting of DNA Test Results by Genomic Companies
 
Reporting of DNA Test Results by Genomic Companies
It is important the DNA test results be reported to beef industry in a consistent,
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It is important the DNA test results be reported to the beef industry in a consistent,
 
understandable format. Further, the format should be compatible with NCE methods. It’s
 
understandable format. Further, the format should be compatible with NCE methods. It’s
 
possible that a single DNA test (i.e., genotypes from a single panel of markers) may
 
possible that a single DNA test (i.e., genotypes from a single panel of markers) may
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An independent organization such as NBCEC should conduct or coordinate the
 
An independent organization such as NBCEC should conduct or coordinate the
validation studies of novel DNA tests. Validation may be approximated by review and
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validation studies of DNA tests for novel traits. Validation may be approximated by review and
 
(or) re-analysis of data used to develop the test. Such data should include DNA test
 
(or) re-analysis of data used to develop the test. Such data should include DNA test
 
results, phenotypes, and pedigree relationships. Data used to develop such new tests
 
results, phenotypes, and pedigree relationships. Data used to develop such new tests
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==Attribution==
 
==Attribution==
Information in this article was derived from Chapter 4 of the 9th edition of the BIF Guidelines. The attribution in that chapter was to: M. W. Tess and the BIF Commission on DNA Markers. Commission members:
+
Information in this article was derived from Chapter 4 of the 9th edition of the BIF Guidelines, with substantial modification for updating to current technology and methods. The attribution in that chapter was to: M. W. Tess and the BIF Commission on DNA Markers. Commission members:
Bill Bowman, Ronnie Green, Ronnie Silcox, Darrell Wilkes, and Jim Wilton.
+
Bill Bowman, Ronnie Green, Ronnie Silcox, Darrell Wilkes, and Jim Wilton. Please view the history link for this article for more information on these modifications.

Latest revision as of 18:28, 12 April 2021

DNA technology has developed rapidly in the past nearly two decades 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 verifications are now routine practices, and genomic data are now routinely used in EPD production. This chapter describes the current uses of DNA technology and provides an overview of applications currently under development.

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. The current standard for identifying genomic markers is single nucleotide polymorphisms (SNPs). Beadarray based "chips" create uniquely identifiable DNA patterns that may be used to follow the transmission of specific chromosomal regions from parents to progeny.

As the name implies, SNPs 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 a 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 in generating data. With the availability of whole-genome sequences, SNPs that are dispersed across all chromosomes present important advantages as markers for genomic 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.

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

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.

Some traits are difficult to measure for which there are currently 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.

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.

Validation

DNA tests are developed based on associations between variations in base-pair sequences at one or more loci with variations in phenotypes. The animal populations used to develop the test may or may not be representative of beef industry populations. Validation generally involves the confirmation or rejection of these associations in populations that are representative of the beef industry and different from those in which the tests were developed. Validation studies are considered to be more reliable if conducted by scientists who have no vested interest in the tests (e.g., development, commercialization, or marketing). To date, components of commercially available DNA tests have been validated by the National Beef Cattle Evaluation Consortium (NBCEC) serving as an independent third party. Validation serves to reduce risk for breeders using DNA tests for selection.

BIF recommends that breeders who use DNA tests should, whenever possible, choose DNA tests that have been validated in populations that are representative of the beef cattle industry by scientists independent of the organization that developed or will market the test.

Assessment

Assessment involves determining how specific DNA tests are associated with each other and with non-target phenotypes. Assessment seeks to determine how competing DNA tests overlap and how non-target traits will be influenced by selection based on these tests. For example, it is important to know if selection based on a DNA test for tenderness has any desirable or adverse effects on other economically important traits (growth, feed intake, fertility, etc.). As with validation, assessment studies are considered to be more reliable if conducted by scientists who have no vested interest in the tests.

BIF recommends that assessment studies should be conducted in populations that are representative of the beef cattle industry by scientists independent of the organization that developed or will market the test.

Inclusion of DNA Test Information in NCE Programs

Statistical procedures for incorporating DNA test information into NCE and the computation of EPD and associated accuracies are described in Single-step Hybrid Marker Effects Models and Single-step Genomic BLUP. Results of the evaluation of a DNA test will also provide estimated genetic correlations among competing DNA tests, genetic correlations between DNA tests and non-target traits, and the fraction of the additive genetic variance of the target trait accounted for by the DNA test.

Results of the evaluation phase (described above) will provide all the statistical parameters needed for NCE. The decision to include a DNA test in a NCE system should be made by the organization responsible for computing the EPD. Consideration should be given to heritability of the trait, availability of producer-collected phenotypes, and increase in accuracy provided by the addition of the DNA test information. BIF recommends that a DNA test should be considered for inclusion in the NCE system when, after estimating the covariances and running the NCE system, use of the DNA test results in more accurate EPD at a young age.

Reporting of DNA Test Results by Genomic Companies It is important the DNA test results be reported to the beef industry in a consistent, understandable format. Further, the format should be compatible with NCE methods. It’s possible that a single DNA test (i.e., genotypes from a single panel of markers) may yield information useful for both management and selection. Predictors based on these tests should be clearly identified with respect to their uses – i.e., future phenotypes versus breeding value.

BIF recommends that DNA test results be reported in the form of an EPD, in units of the trait, on a continuous scale, and with a corresponding BIF accuracy. It is likely that research will develop new DNA tests for traits that have no industry-collected phenotypes. If the target trait is measured in the reference populations, evaluation of the DNA test as a selection tool should be as described above.

Novel Traits

It’s conceivable that the target traits for some new DNA tests may not be measured in reference populations. In such cases precise definition of the target trait will be important.

An independent organization such as NBCEC should conduct or coordinate the validation studies of DNA tests for novel traits. Validation may be approximated by review and (or) re-analysis of data used to develop the test. Such data should include DNA test results, phenotypes, and pedigree relationships. Data used to develop such new tests should be of sufficient quality and quantity to allow the estimation of the additive genetic variance of the target trait and the covariance between the DNA test score and the target trait.

BIF recommends that, for DNA tests targeting traits that have no industry-collected phenotypes and for which no phenotypes are collected in reference populations, results should be reported in the form of an EPD, in the units of the trait, on a continuous scale, and with a corresponding BIF accuracy.

Attribution

Information in this article was derived from Chapter 4 of the 9th edition of the BIF Guidelines, with substantial modification for updating to current technology and methods. The attribution in that chapter was to: M. W. Tess and the BIF Commission on DNA Markers. Commission members: Bill Bowman, Ronnie Green, Ronnie Silcox, Darrell Wilkes, and Jim Wilton. Please view the history link for this article for more information on these modifications.