Brief Summary of Minutes of Annual Meeting

The NCR204 project convened Saturday February 8, 2003 in Ventura, California just prior to the Gordon Conference. William Muir (Chair) restated the administrative structure and the three project objectives. Margaret Dentine (Administrative Advisor) emphasized that the expected outcomes are important and include 1) workshops 2) publicly available software and 3) joint grant and joint papers. The importance of regular attendance was noted, as well as the requirement to fill out and sign appendix E. Richard Fram (the CREES representative) has retired and no replacement is anticipated anytime soon.

The business meeting consisted of discussions on the next meeting place, terms of office, elections, successions, appointments and policies, structure, rules and governance. Guilherme Rosa, Jack Dekkers, and Shizhong Xu were appointed coordinators for objectives 1, 2, and 3 respectively. The new chair is Jeanne Romero-Severson. The new secretary is Jean Luc Jannick.

Xu, Misztal, Saxton, Rosa, Walsh, Romero-Severson, Muir, Dudley, Dekkers and Bailey gave station reports. All stations that are members reported, if the AA report may be counted as Wisconsins report. These stations are UC Riverside, University of Georgia, University of Tennessee, Michigan State, University of Arizona, Purdue University, University of Illinois, Iowa State and University of Wisconsin.

Objective 1: Develop and compare statistical methodology to map genes

Xu (UC Riverside) showed that a Baysian method under the random regression coefficient model can handle a large number of markers in a single model and deal with markers with close to zero expected effect. The Bayesian method produces the L-shaped distribution predicted by the oligogenic hypothesis, wherein most markers have very small or zero effects, while a small number of markers account for most of the observed phenotypic variance.

Rosa (Michigan State) used Baysian methods to construct genetic maps and assigning parentage assuming a genotyping error rate between 1-5%. The Baysian approach delivers a more accurate estimate of gene order, minimizes false exclusion due to genotyping errors and can determine whether or not a DNA sample contains a mixture of genotypes (i.e. more than 1 individual). Dudley (University of Illinois) indicated that random mating an F2 population preserves genetic variance while breaking up parental linkage blocks. The increase in the number of observable recombinations enables more precise estimates of QTL location provided that the population size genotyped is large enough to accommodate the additional markers that must added to prevent linkage map decomposition (the breaking apart of linkage groups due to map expansion).

Dekkers (Iowa State) described how DNA pooling of phenotypic extremes within half-sib families reduces the genotyping burden while permitting estimation of QTL position and effect with minimal loss of power. Least squares interval mapping analysis of pooling data (pool-LSIM) gave high power to detect the QTL (>97%) when family size was large and moderate power (>55%) for small families. For small families, pool-LSIM had up to 14% greater power than single marker analysis, except for distal QTL with known VTE (technical error variance).

Objective 2: Examine the efficiency of incorporating molecular tools in breeding programs through theoretical modeling, computer simulations, and biological testing in actual breeding populations.

1. Microarrays. Rosa summarized the current state of microarray analysis. Different statistical tools have been proposed for the normalization (both location and scale normalizations) and analysis of microarray data, including clustering methods and significance tests, such as permutation-based t-statistics, linear (fixed or mixed) models, mixture models and non-parametric methods.

Saxton (U Tennessee) reported that a combination of microarrays, genotyping and cloning is being used in a project aimed at increased genetic resistance to mastitis in dairy cattle. The design and interpretation of microarray data remains a problem.

Romero-Severson (Purdue) showed that Bonferroni correction, as applied to simple t tests of pairwise comparisons from Affymetrix microarray data, is too conservative. An ad hoc method followed by qRT-PCR found 12 genes with expression differences in excess of 2x for both of the planned comparisons and appropriate tissue specificity. The design included true biological replication and two treatments but was not analyzed using standard statistical models because of the problem posed by autocorrelation among the entries. Autocorrelation was the explanation offered for the failure of the Bonferroni correction.

2. Breeding techniques and statistical theory. Misztal (U Georgia) examined poultry and dairy cow performance data for changes in genetic correlations among performance traits as selection proceeds. Random regression models (RRM) with regressions on functions of year of birth or year of first recording detected large changes in genetic correlations in Holstein breeding programs. Inaccurate genetic correlations will weaken the predictive value of gain from selection estimates.

Muir (Purdue) used computer simulations and real data to show that direct selection for performance traits tends to select those genotypes that require high input and reduced competition (more space, more fertilizer, more feed). Inclusion of the associative effects of one organism on another in the selection scheme allows selection for tolerance of competition and increased performance. Quail experiments showed that reducing the associative effects results in more gain that selecting on direct effects alone. This concept can be applied to plantation forestry and also permits QTL mapping for associative effects.

Dudley reported that genetic variance in the long term selection experiments has persisted longer than many anticipated. Current hypotheses include the new mutation theory, which implies that genetic variance for a quantitative trait will not disappear under selection in the absence of genetic drift and nonrandom mating.

Objective 3: Use molecular genetics to test hypotheses generated from the fundamental theories of population, quantitative, molecular and evolutionary genetics.

Bruce Walsh described the theory that gene duplication generates genetic variation through neofunctionalization (retention of the old function and addition of a new function) and subfunctionalization (partition of the original function into conditional functions which differ between the two genes). The third possibility, loss of function through gene silencing, will eventually result in a pseudogene as mutations accumulate. The probability of neofunctionalization is a function of the selection coefficient and the effective population size. Tandem duplication followed by chromosome rearrangement then neofunctionalization can break up linkage relationships, while subfunctionalization can reduce potential pleiotropic constraints. In both cases, the change allows testing of new physical and functional combinations

Georgia

Tsuruta. S., I. Misztal, T. J. Lawlor, and B. Klei. 2002. Application of a Random Regression Model at Different Ages for Final Scores in Holsteins. J. Dairy Sci. 85:1324:1330.

Stranden, I., S. Tsuruta, and I. Misztal. 2002. Simple preconditioners for the conjugate gradient method: experience with the test day model. J. Anim. Breeding Genet. 119 (3):166_174.

Misztal, I., S. Tsuruta,T. Strabel, B. Auvray, T. Druet, and D. H. Lee. 2002. BLUPF90 and related programs (BGF90). Proc. 7th World Congress Gen. Appl. Livest. Prod., Monteplier, France. CD_ROM communication 28:07.

Lawlor, T. J., S. Tsuruta, L. Klei and I. Misztal. 2002. Use of a random regression model to investigate changes in genetic parameters over time. Proc. 7th World Congress Gen. Appl. Livest. Prod., Monteplier, France. CD_ROM communication 17:06.

Tsuruta S., I. Misztal, T. J. Lawlor, and L. Klei. 2002. Estimation of genetic parameters over time for final score in holsteins using a random regression model. Proc. 7th World Congress Gen. Appl. Livest. Prod., Monteplier, France. CD_ROM communication 17:20.

Misztal I., S. Tsuruta, T. J. Lawlor, and L. Klei. 2002. Use of a random regression model to investigate changes in genetic parameters over time. 18th Panamerican Congress of Veterinary Sciences, Havana, Cuba. CDROM communication.

Tsuruta, S., I. Misztal, T. J. Lawlor, and L. Klei. 2002. Changes of genetic correlation between milk production and body size over time in Holsteins using random regression models. J. Dairy Sci (Suppl. 1) 85: 197.

Michigan State

Rosa, G. J. M., Yandell, B. S., Gianola, D. A Bayesian approach for constructing genetic maps when markers are miscoded. Genetic, Selection, Evolution, 34(3): 353-369. 2002.

Coussens, P. M., Colvin, C. J., Rosa, G. J. M., Laspiur, J. P., Elftman, M. D. Novel gene expression differences in peripheral blood mononuclear cells from M. paratuberculosis infected and control cattle. Infection and Immunity (submitted)

Madsen, S. A., Rosa, G. J. M., Mccandless, E., Coussens, P. M., Burton, J. L. Microarray analysis of mRNA profiles in neutrophils from periparturient cows reveals a novel phenotype. Veterinary Immunology and Immunopathology (submitted)

Rosa, G. J. M., Gianola, D., Padovani, C. R. Robust linear mixed models with normal/independent distributions and Bayesian MCMC implementation. Biometrical Journal. (accepted)




Tennessee

Stalder, K. J., A. M. Saxton, R. K. Miller, and R. N. Goodwin. 2003. A comparison of hydrogen ion concentration and pH genetic predictions and fixed effect estimations when assessing pork quality. J. Anim. Sci. 81(3): 611-616.

Smiley, R.D., L.G. Stinnett, A.M. Saxton, and E.E. Howell. 2002. Breaking Symmetry: Mutations Engineered into R67 Dihydrofolate Reductase, A D2 Symmetric Homotetramer Possessing a Single Active Site Pore. Biochemistry 41(52): 15664-15675.

Pighetti, G. M., J. L. Edwards, F. N. Schrick, A. M. Saxton, C. J. Davies, and S. P. Oliver. 2003. Cloning adult dairy cows: A viable new tool in the fight against mastitis. National Mastitis Council Annual Meeting.

Youngerman, S. M., S. P. Oliver, A. M. Saxton, J. L. Edwards, F. N. Schrick, C. J. Davies, and G. M. Pighetti. 2003. Interleukin-8 receptor: A candidate gene for mastitis resistance. National Mastitis Council Annual Meeting.


Purdue

Muir, W.M. and R.D. Howard. 2002. Methods to Assess Ecological Risks of Transgenic Fish Releases. In Genetically Engineered Organisms: Assessing Environmental and Human Health Effects Eds. D.K. Letourneau and B. E. Burrows. CRC Press p355-383.

Muir, WM and R.D. Howard 2002. Environmental Risk Assessment of Transgenic Fish With Implications for Other Diploid Organisms. Transgenic Research 11:101-114.

Muir, W.M. 2002. Potential Environmental Risks And Hazards Of Biotechnology. Potential Environmental Risks And Hazards Of Biotechnology Part I: Risks and Hazards. http://www.isb.vt.edu/news/2001/news01.nov.html#nov0105. Information Systems For Biotechnology (online version)

Muir, W.M. 2002. Potential Environmental Risks And Hazards Of Biotechnology.Part II: Methods to Estimate Risks and Hazards http://www.isb.vt.edu/news/2002/news02.feb.html#feb0201. Information Systems For Biotechnology (online version)

Muir, W.M. and A. Schinckel. 2002. Incorporation of competitive effects in breeding programs to improve productivity and animal well being. Proc. 7th World Congress of Genetics Applied to Livestock Breeding. 32:35-36

Muir, W.M. 2002. Use of molecular genetics in poultry breeding. Proc. 7th World Congress of Genetics Applied to Livestock Breeding. 30:193-200

NRC (National Research Council). 2002. Animal Biotechnology: Science Based Concerns. Washington, DC: National Academy Press.

Muir, W.M.. 2002. Indirect Selection for Improvement of Animal Well-Being. In Poultry Breeding and Biotechnology Eds. WM Muir and S Aggrey. CABI Press (in press).

Muir, W.M.. 2002. Incorporating Molecular Information in Breeding Programs, Applications and Limitations. In Poultry Breeding and Biotechnology Eds. WM Muir and S Aggrey. CABI Press (in press).

Muir, W.M., D. Miles, and A.E. Bell, 2002. Long Term Selection Studies In Tribolium Castaneum, Alternative Selection Strategies, And Associated Nature Of Quantitative Genetic Variation. Plant Breeding Reviews (In Press)

Rider, Sj Jr, TE Henderson, RE Jerome. HJ Edenberg, J Romero-Severson, J Ogas. 2003 Coordinate Repression of Regulators of Embryonic Identity by PICKLE During Germination in Arabidopsis. The Plant Journal. In press.


Iowa

Chaiwong, N., J.C.M. Dekkers, R.L. Fernando, and M.F. Rothschild. 2002. Introgressing multiple QTL in backcross breeding programs of limited size. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 22:08.

Chakraborty, R., L. Moreau, and J. C. M. Dekkers. 2002. A method to optimize selection on multiple identified quantitative trait loci. Genet. Sel. Evol. 34: 145-170.

Cruickshank, J., M. R. Dentine, P. J. Berger, and B. W. Kirkpatrick. 2002. Mapping quantitative trait loci for twinning in Holstein dairy cattle. Proc. 28th Intl. Conf. Anim. Genet. p. 164. Goettingen, Germany.

Dekkers, J. C. M. and P. Settar. 2002. Long-term Selection with Known Quantitative Trait Loci. Plant Breeding Reviews. Wiley. (Accepted).

Dekkers, J. C. M., R. Chakraborty, and L. Moreau. 2002. Optimal selection on two quantitative trait loci with linkage. Genet. Sel. Evol. 34 171-192.

Dekkers, J.C.M., and R. Chakraborty. 2002. Purebred selection for crossbred performance using QTL. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 22:15.

Fernandez, S. A., and R. L. Fernando. 2002. Determining Peeling Order Using Sparse Matrix Algorithms. J. Dairy Sci. 85:1623-1629.

Fernandez, S. A., R. L. Fernando, B. Gulbrandtsen, C. Stricker, M. Schelling, and A. L. Carriquiry. 2002. Irreducibility and efficiency of ESIP to sample marker genotypes in large pedigrees with loops. Genet. Sel Evol. 34:537-555.

Fernando, R. L. and L. R. Totir. 2002. Advances in genetic and statistical models to predict breeding values. 7th World Congress Genet. Appl. Livest.\Prod. 20-01.

Fernando, R. L., J. C. M. Dekkers and M. Soller. 2002. Controlling the proportion of false positives (PFP) in a multiple test genome scan for marker-QTL linkage. 7th World Congress Genet. Appl. Livest. Prod. 20-01.

Fernando, R.L., J.C.M. Dekkers, and M. Soller. 2002. Controlling the proportion of false positive (PFP) in a multiple test genome scan for marker-QTL linkage. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 21:37.

Grapes, L., R. L. Fernando and M. F. Rothschild. 2002. Analysis of methods for fine mapping quantitative trait loci using linkage disequilibrium. 7th Wld Congress Genet. Appl. Livest. Prod. 21-19.

Heifetz, E., R. L. Fernando and M. Soller. 2002. Targeted recombinant progeny: a design for ultra high-resolution mapping of QTL using a saturated marker map. 7th World Congress Genet. Appl. Livest. Prod. 21-25.

Hwang, J. T. G. and Nettleton, D. (2003). Principal components regression with data-chosen components and related methods. Accepted for publication in Technometrics.

Jannink, J.-L. 2003. Selection dynamics and limits under additive-by-additive epistatic gene action. Crop Sci. 43: In Press.

Jannink, J.-L., and X.-L. Wu. 2003. Estimating allelic number and identity in state of QTL in interconnected families. Genet. Res. 81: In Press.

Jansen, R.C., J.-L. Jannink, and W.D. Beavis. 2003. Mapping quantitative trait loci in plant breeding populations: use of parental haplotype sharing. Crop Sci. 43:In Press.

Kachman, S. D. and R. L. Fernando. 2002. Analysis of generalized linear models with MATVEC. 7th World Congress Genet. Appl. Livest. Prod. 28-04.

Lee, H.K., J.C.M. Dekkers, M. Soller, M. Malek, R.L. Fernando, and M.F. Rothschild, 2002. Application of the false discovery rate to QTL interval mapping with multiple traits. Genetics 161: 905-914.

McElroy, J.P., D.E. Harry, J.C.M. Dekkers, and S.J. Lamont. 2002. Molecular markers associated with growth and carcass traits in meat-type chickens. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 04:04.

Settar, P., J.C.M. Dekkers, and H.A.M. van der Steen. 2002. Control of QTL frequency in breeding populations. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 23:04.

Stricker, C., M. Schelling, F. Du, I. Hoeschelle, S. A. Fernandez and R. L. Fernando. 2002. A comparison of efficient genotype samplers for complex pedigrees and multiple linked loci. 7th World Congress Genet. Appl. Livest. Prod. 21-12.

Thomsen, H., J.C.M. Dekkers, H.K. Lee, and M.F. Rothschild. 2002. Characterisation of quantitative loci for growth and meat quality in a breed cross in swine. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 15:05.

Totir, L.R., R.L. Fernando, J.C.M. Dekkers, and S.A. Fernandez. 2002. A strategy to improve the computational efficiency of marker assisted genetic evaluation under finite locus models. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 16:02.

Villanueva, B., J.C.M. Dekkers, J.A. Woolliams, and P. Settar. 2002. Maximising genetic gain with QTL information and control of inbreeding. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 22:18.

Wang, J., M. Soller, and J.C.M. Dekkers. 2002. Mapping QTL with selective DNA pooling by least squares interval mapping. 2002. 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France, 21:08.
Minnesota

SOFTWARE RELEVANT TO NCR-204

GMO Risk Assessment Using Net Fitness Components Approach
Available at http://web.ics.purdue.edu/~bmuir/
Author: William Muir


COURSES GIVEN ON STATISTICAL GENETICS

ANS 824: Methods of Quantitative and Molecular Genetics for Livestock. Spring 2003. Credits 1-0, Michigan State University. Guillerme Rosa.

ANS 890/901: Design and analysis of microarray gene expression experiments. Fall 2002. Credits 1-0, Michigan State University. Guillerme Rosa.