Genome-wide association study to identify chromosomal regions associated with antibody response to Mycobacterium avium subspecies paratuberculosis in milk of Dutch Holstein-Friesians
Hulzen, K.J.E. van; Schopen, G.C.B. ; Arendonk, J.A.M. van; Nielen, M. ; Koets, A.P. ; Schrooten, C. ; Heuven, H.C.M. - \ 2012
Journal of Dairy Science 95 (2012)5. - ISSN 0022-0302 - p. 2740 - 2748.
single nucleotide polymorphisms - estimated breeding values - quantitative trait loci - genetic-variation - johnes-disease - linkage disequilibrium - short-communication - us holsteins - infection - cattle
Heritability of susceptibility to Johne's disease in cattle has been shown to vary from 0.041 to 0.159. Although the presence of genetic variation involved in susceptibility to Johne's disease has been demonstrated, the understanding of genes contributing to the genetic variance is far from complete. The objective of this study was to contribute to further understanding of genetic variation involved in susceptibility to Johne's disease by identifying associated chromosomal regions using a genome-wide association approach. Log-transformed ELISA test results of 265,290 individual Holstein-Friesian cows from 3,927 herds from the Netherlands were analyzed to obtain sire estimated breeding values for Mycobacterium avium subspecies paratuberculosis (MAP)-specific antibody response in milk using a sire-maternal grandsire model with fixed effects for parity, year of birth, lactation stage, and herd; a covariate for milk yield on test day; and random effects for sire, maternal grandsire, and error. For 192 sires with estimated breeding values with a minimum reliability of 70%, single nucleotide polymorphism (SNP) typing was conducted by a multiple SNP analysis with a random polygenic effect fitting 37,869 SNP simultaneously. Five SNP associated with MAP-specific antibody response in milk were identified distributed over 4 chromosomal regions (chromosome 4, 15, 18, and 28). Thirteen putative SNP associated with MAP-specific antibody response in milk were identified distributed over 10 chromosomes (chromosome 4, 14, 16, 18, 19, 20, 21, 26, 27, and 29). This knowledge contributes to the current understanding of genetic variation involved in Johne's disease susceptibility and facilitates control of Johne's disease and improvement of health status by breeding.
The impact of genotyping different groups of animals on accuracy when moving from traditional to genomic selection
Pszczola, M.J. ; Strabel, T. ; Arendonk, J.A.M. van; Calus, M.P.L. - \ 2012
Journal of Dairy Science 95 (2012)9. - ISSN 0022-0302 - p. 5412 - 5421.
estimated breeding values - relationship matrices - genetic evaluation - full pedigree - dairy-cattle - unified approach - holstein cattle - information - populations - prediction
Compared with traditional selection, the use of genomic information tends to increase the accuracy of estimated breeding values (EBV). The cause of this increase is, however, unknown. To explore this phenomenon, this study investigated whether the increase in accuracy when moving from traditional (AA) to genomic selection (GG) was mainly due to genotyping the reference population (GA) or the evaluated animals (AG). In it, a combined relationship matrix for simultaneous use of genotyped and ungenotyped animals was applied. A simulated data set reflected the dairy cattle population. Four differently designed (i.e., different average relationships within the reference population) small reference populations and 3 heritability levels were considered. The animals in the reference populations had high, moderate, low, and random (RND) relationships. The evaluated animals were juveniles. The small reference populations simulated difficult or expensive to measure traits (i.e., methane emission). The accuracy of selection was expressed as the reliability of (genomic) EBV and was predicted based on selection index theory using relationships. Connectedness between the reference populations and evaluated animals was calculated using the prediction error variance. Average (genomic) EBV reliabilities increased with heritability and with a decrease in the average relationship within the reference population. Reliabilities in AA and AG were lower than those in GG and were higher than those in GA (respectively, 0.039, 0.042, 0.052, and 0.048 for RND and a heritability of 0.01). Differences between AA and GA were small. Average connectedness with all animals in the reference population for all scenarios and reference populations ranged from 0.003 to 0.024; it was lowest when the animals were not genotyped (AA; e.g., 0.004 for RND) and highest when all the animals were genotyped (GG; e.g., 0.024 for RND). Differences present across designs of the reference populations were very small. Genomic relationships among animals in the reference population might be less important than those for the evaluated animals with no phenotypic observations. Thus, the main origin of the gain in accuracy when using genomic selection is due to genotyping the evaluated animals. However, genotyping only one group of animals will always yield less accurate estimates.
Reliability of direct genomic values for animals with different relationships within and to the reference population
Pszczola, M.J. ; Strabel, T. ; Mulder, H.A. ; Calus, M.P.L. - \ 2012
Journal of Dairy Science 95 (2012)1. - ISSN 0022-0302 - p. 389 - 400.
quantitative trait loci - genetic-relationship information - estimated breeding values - dairy-cattle - linkage disequilibrium - holstein population - selection - accuracy - association - predictions
Accuracy of genomic selection depends on the accuracy of prediction of single nucleotide polymorphism effects and the proportion of genetic variance explained by markers. Design of the reference population with respect to its family structure may influence the accuracy of genomic selection. The objective of this study was to investigate the effect of various relationship levels within the reference population and different level of relationship of evaluated animals to the reference population on the reliability of direct genomic breeding values (DGV). The DGV reliabilities, expressed as squared correlation between estimated and true breeding value, were calculated for evaluated animals at 3 heritability levels. To emulate a trait that is difficult or expensive to measure, such as methane emission, reference populations were kept small and consisted of females with own performance records. A population reflecting a dairy cattle population structure was simulated. Four chosen reference populations consisted of all females available in the first genotyped generation. They consisted of highly (HR), moderately (MR), or lowly (LR) related animals, by selecting paternal half-sib families of decreasing size, or consisted of randomly chosen animals (RND). Of those 4 reference populations, RND had the lowest average relationship. Three sets of evaluated animals were chosen from 3 consecutive generations of genotyped animals, starting from the same generation as the reference population. Reliabilities of DGV predictions were calculated deterministically using selection index theory. The randomly chosen reference population had the lowest average relationship within the reference population. Average reliabilities increased when average relationship within the reference population decreased and the highest average reliabilities were achieved for RND (e.g., from 0.53 in HR to 0.61 in RND for a heritability of 0.30). A higher relationship to the reference population resulted in higher reliability values. At the average squared relationship of evaluated animals to the reference population of 0.005, reliabilities were, on average, 0.49 (HR) and 0.63 (RND) for a heritability of 0.30; 0.20 (HR) and 0.27 (RND) for a heritability of 0.05; and 0.07 (HR) and 0.09 (RND) for a heritability of 0.01. Substantial decrease in the reliability was observed when the number of generations to the reference population increased [e.g., for heritability of 0.30, the decrease from evaluated set I (chosen from the same generation as the reference population) to II (one generation younger than the reference population) was 0.04 for HR, and 0.07 for RND]. In this study, the importance of the design of a reference population consisting of cows was shown and optimal designs of the reference population for genomic prediction were suggested.