Publications by authors named "Gerben de Jong"

7 Publications

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Genome-wide fine-mapping identifies pleiotropic and functional variants that predict many traits across global cattle populations.

Nat Commun 2021 02 8;12(1):860. Epub 2021 Feb 8.

Faculty of Veterinary and Agricultural Science, The University of Melbourne, Parkville, VIC, Australia.

The difficulty in finding causative mutations has hampered their use in genomic prediction. Here, we present a methodology to fine-map potentially causal variants genome-wide by integrating the functional, evolutionary and pleiotropic information of variants using GWAS, variant clustering and Bayesian mixture models. Our analysis of 17 million sequence variants in 44,000+ Australian dairy cattle for 34 traits suggests, on average, one pleiotropic QTL existing in each 50 kb chromosome-segment. We selected a set of 80k variants representing potentially causal variants within each chromosome segment to develop a bovine XT-50K genotyping array. The custom array contains many pleiotropic variants with biological functions, including splicing QTLs and variants at conserved sites across 100 vertebrate species. This biology-informed custom array outperformed the standard array in predicting genetic value of multiple traits across populations in independent datasets of 90,000+ dairy cattle from the USA, Australia and New Zealand.
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http://dx.doi.org/10.1038/s41467-021-21001-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870883PMC
February 2021

Improving Genomic Prediction of Crossbred and Purebred Dairy Cattle.

Front Genet 2020 14;11:598580. Epub 2020 Dec 14.

AgriBio Centre for AgriBioscience, Agriculture Victoria Services, Bundoora, VIC, Australia.

This study assessed the accuracy and bias of genomic prediction (GP) in purebred Holstein (H) and Jersey (J) as well as crossbred (H and J) validation cows using different reference sets and prediction strategies. The reference sets were made up of different combinations of 36,695 H and J purebreds and crossbreds. Additionally, the effect of using different sets of marker genotypes on GP was studied (conventional panel: 50k, custom panel enriched with, or close to, causal mutations: XT_50k, and conventional high-density with a limited custom set: pruned HDnGBS). We also compared the use of genomic best linear unbiased prediction (GBLUP) and Bayesian (emBayesR) models, and the traits tested were milk, fat, and protein yields. On average, by including crossbred cows in the reference population, the prediction accuracies increased by 0.01-0.08 and were less biased (regression coefficient closer to 1 by 0.02-0.16), and the benefit was greater for crossbreds compared to purebreds. The accuracy of prediction increased by 0.02 using XT_50k compared to 50k genotypes without affecting the bias. Although using pruned HDnGBS instead of 50k also increased the prediction accuracy by about 0.02, it increased the bias for purebred predictions in emBayesR models. Generally, emBayesR outperformed GBLUP for prediction accuracy when using 50k or pruned HDnGBS genotypes, but the benefits diminished with XT_50k genotypes. Crossbred predictions derived from a joint pure H and J reference were similar in accuracy to crossbred predictions derived from the two separate purebred reference sets and combined proportional to breed composition. However, the latter approach was less biased by 0.13. Most interestingly, using an equalized breed reference instead of an H-dominated reference, on average, reduced the bias of prediction by 0.16-0.19 and increased the accuracy by 0.04 for crossbred and J cows, with a little change in the H accuracy. In conclusion, we observed improved genomic predictions for both crossbreds and purebreds by equalizing breed contributions in a mixed breed reference that included crossbred cows. Furthermore, we demonstrate, that compared to the conventional 50k or high-density panels, our customized set of 50k sequence markers improved or matched the prediction accuracy and reduced bias with both GBLUP and Bayesian models.
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http://dx.doi.org/10.3389/fgene.2020.598580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767986PMC
December 2020

Inbreeding depression across the genome of Dutch Holstein Friesian dairy cattle.

Genet Sel Evol 2020 Oct 28;52(1):64. Epub 2020 Oct 28.

Animal Breeding and Genomics, Wageningen University and Research, P.O. Box 338, 6700 AH, Wageningen, The Netherlands.

Background: Inbreeding depression refers to the decrease in mean performance due to inbreeding. Inbreeding depression is caused by an increase in homozygosity and reduced expression of (on average) favourable dominance effects. Dominance effects and allele frequencies differ across loci, and consequently inbreeding depression is expected to differ along the genome. In this study, we investigated differences in inbreeding depression across the genome of Dutch Holstein Friesian cattle, by estimating dominance effects and effects of regions of homozygosity (ROH).

Methods: Genotype (75 k) and phenotype data of 38,792 cows were used. For nine yield, fertility and udder health traits, GREML models were run to estimate genome-wide inbreeding depression and estimate additive, dominance and ROH variance components. For this purpose, we introduced a ROH-based relationship matrix. Additive, dominance and ROH effects per SNP were obtained through back-solving. In addition, a single SNP GWAS was performed to identify significant additive, dominance or ROH associations.

Results: Genome-wide inbreeding depression was observed for all yield, fertility and udder health traits. For example, a 1% increase in genome-wide homozygosity was associated with a decrease in 305-d milk yield of approximately 99 kg. For yield traits only, including dominance and ROH effects in the GREML model resulted in a better fit (P < 0.05) than a model with only additive effects. After correcting for the effect of genome-wide homozygosity, dominance and ROH variance explained less than 1% of the phenotypic variance for all traits. Furthermore, dominance and ROH effects were distributed evenly along the genome. The most notable region with a favourable dominance effect for yield traits was on chromosome 5, but overall few regions with large favourable dominance effects and significant dominance associations were detected. No significant ROH-associations were found.

Conclusions: Inbreeding depression was distributed quite equally along the genome and was well captured by genome-wide homozygosity. These findings suggest that, based on 75 k SNP data, there is little benefit of accounting for region-specific inbreeding depression in selection schemes.
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http://dx.doi.org/10.1186/s12711-020-00583-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594306PMC
October 2020

Inbreeding depression due to recent and ancient inbreeding in Dutch Holstein-Friesian dairy cattle.

Genet Sel Evol 2019 Sep 27;51(1):54. Epub 2019 Sep 27.

Wageningen University & Research, Animal Breeding and Genomics, P.O. Box 338, 6700 AH, Wageningen, The Netherlands.

Background: Inbreeding decreases animal performance (inbreeding depression), but not all inbreeding is expected to be equally harmful. Recent inbreeding is expected to be more harmful than ancient inbreeding, because selection decreases the frequency of deleterious alleles over time. Selection efficiency is increased by inbreeding, a process called purging. Our objective was to investigate effects of recent and ancient inbreeding on yield, fertility and udder health traits in Dutch Holstein-Friesian cows.

Methods: In total, 38,792 first-parity cows were included. Pedigree inbreeding ([Formula: see text]) was computed and 75 k genotype data were used to compute genomic inbreeding, among others based on regions of homozygosity (ROH) in the genome ([Formula: see text]).

Results: Inbreeding depression was observed, e.g. a 1% increase in [Formula: see text] was associated with a 36.3 kg (SE = 2.4) decrease in 305-day milk yield, a 0.48 day (SE = 0.15) increase in calving interval and a 0.86 unit (SE = 0.28) increase in somatic cell score for day 150 through to 400. These effects equalled - 0.45, 0.12 and 0.05% of the trait means, respectively. When [Formula: see text] was split into generation-based components, inbreeding on recent generations was more harmful than inbreeding on more distant generations for yield traits. When [Formula: see text] was split into new and ancestral components, based on whether alleles were identical-by-descent for the first time or not, new inbreeding was more harmful than ancestral inbreeding, especially for yield traits. For example, a 1% increase in new inbreeding was associated with a 2.42 kg (SE = 0.41) decrease in 305-day fat yield, compared to a 0.03 kg (SE = 0.71) increase for ancestral inbreeding. There were no clear differences between effects of long ROH (recent inbreeding) and short ROH (ancient inbreeding).

Conclusions: Inbreeding depression was observed for yield, fertility and udder health traits. For yield traits and based on pedigree, inbreeding on recent generations was more harmful than inbreeding on distant generations and there was evidence of purging. Across all traits, long and short ROH contributed to inbreeding depression. In future work, inbreeding depression and purging should be assessed in more detail at the genomic level, using higher density information and genomic time series.
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http://dx.doi.org/10.1186/s12711-019-0497-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764141PMC
September 2019

Joint replacement rehabilitation and the role of funding source.

J Rehabil Med 2019 Oct;51(10):770-778

Orthopaedic Surgery and Musculoskeletal Medicine, University of Otago, , 8011 Christchurch, New Zealand.

Objective: To examine associations between funding source, use of rehabilitation and outcomes after total joint replacement and to evaluate variations based on demographic characteristics.

Design: Cross-sectional, questionnaire-based national survey.

Subjects: Participants aged 45 years or older (n = 522) who received either private or public funding for their surgery, were recruited from the New Zealand Joint Registry 6 months after a total hip, total knee or unicompartmental knee replacement.

Results: The cohort was predominantly New Zealand European (90%), aged 68 years, with more men (55%) than women (45%). Privately funded participants were younger, had higher levels of education and employment, and lower rates of comorbidities at the time of surgery. Privately funded participants also reported spending less time on the surgical waiting list, were less likely to participate in pre-surgical rehabilitation, but reported more weeks of post-surgical rehabilitation and better patient-reported outcomes in terms of pain, function and quality of life, compared with their publicly funded counterparts.

Conclusion: Factors already known to impact on joint replacement outcomes were associated with funding source in this cohort. Socio-economic differences and inequities between private and public systems exist consistent with limited available prior research. In this cross-sectional study, no clinically significant differences in outcomes between the groups were identified. Prospective research will help to clarify whether funding source directly affects joint replacement rehabilitation outcomes.
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http://dx.doi.org/10.2340/16501977-2600DOI Listing
October 2019

A deletion in the bovine FANCI gene compromises fertility by causing fetal death and brachyspina.

PLoS One 2012 29;7(8):e43085. Epub 2012 Aug 29.

Unit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of Liège (B34), Liège, Belgium.

Fertility is one of the most important traits in dairy cattle, and has been steadily declining over the last decades. We herein use state-of-the-art genomic tools, including high-throughput SNP genotyping and next-generation sequencing, to identify a 3.3 Kb deletion in the FANCI gene causing the brachyspina syndrome (BS), a rare recessive genetic defect in Holstein dairy cattle. We determine that despite the very low incidence of BS (<1/100,000), carrier frequency is as high as 7.4% in the Holstein breed. We demonstrate that this apparent discrepancy is likely due to the fact that a large proportion of homozygous mutant calves die during pregnancy. We postulate that several other embryonic lethals may segregate in livestock and significantly compromise fertility, and propose a genotype-driven screening strategy to detect the corresponding deleterious mutations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043085PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430679PMC
February 2013

Genetic parameters for clinical mastitis in the first three lactations of Dutch Holstein cattle.

Vet Microbiol 2009 Feb 12;134(1-2):165-71. Epub 2008 Sep 12.

NRS, Animal Evaluation Unit, 6800 AL Arnhem, The Netherlands.

The first breeding value for udder health of a bull is based on the performance of his daughters in their first lactation. However, clinical mastitis (CM) is not a problem in first lactation only. Therefore, the objective of this study was to estimate genetic parameters for CM and somatic cell count (SCC) for the first three lactations of Dutch Holstein cattle. Data from 250 Dutch herds recording CM were used to quantify the genetic variation of CM in parity 1, 2, and 3, respectively. The dataset contained 35,379 lactations from 21,064 animals of different parities. Test-day SCC was available from all lactations. Somatic cell counts were log-transformed to somatic cell scores (SCS) and averaged over test-day records between 5 and 335, 5 and 150, and 151 and 335 days in milk. Variance components for CM and SCS were estimated using a sire-maternal grandsire model. The heritability for CM was approximately 3% in all parities. Genetic correlations between CM in consecutive lactations were high (0.9), but somewhat lower between parity 1 and 3 (0.6). All genetic correlations between CM and SCS were positive, implying that genetic selection on lower SCC will reduce CM-incidence. Estimated genetic correlations were stronger for SCS in the first half of lactation than in the second half of lactation. Selection indices showed that most progress could be achieved when treating CM in parity 1, 2, and 3 as different traits and by including SCS between 5 and 150 days in the udder health index.
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http://dx.doi.org/10.1016/j.vetmic.2008.09.024DOI Listing
February 2009
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