A splice-acceptor site variant in the bovine PIGH gene causes glycosylphosphatidyl inositol deficiency and lethal arthrogryposis syndrome.

Poster (2013, January 28)

A missense mutation in the ClC-7 chloride channel causes hamartomas with osteopetrosis in cattle.

Conference (2012, October 19)

A missense mutation in the ClC-7 chloride channel causes hamartomas with osteopetrosis in cattle.

Conference (2012, June 05)

A splice site variant in the bovine RNF11 gene compromises growth and regulation of the inflammatory response.

in PLoS Genetics (2012), 15(3), 1002581

We herein report association mapping of a locus on bovine chromosome 3 that underlies a Mendelian form of stunted growth in Belgian Blue Cattle. By resequencing positional candidates, we identify the ... [more ▼]

We herein report association mapping of a locus on bovine chromosome 3 that underlies a Mendelian form of stunted growth in Belgian Blue Cattle. By resequencing positional candidates, we identify the causative c124-2A>G splice variant in intron 1 of the RNF11 gene, for which all affected animals are homozygous. We make the remarkable observation that 26% of healthy Belgian Blue animals carry the corresponding variant. We demonstrate in a prospective study design that approximately one third of homozygous mutants die prematurely with major inflammatory lesions, hence explaining the rarity of growth-stunted animals despite the high frequency of carriers. We provide preliminary evidence that heterozygous advantage for an as of yet unidentified phenotype may have caused a selective sweep accounting for the high frequency of the RNF11 c124-2A>G mutation in Belgian Blue Cattle. [less ▲]

Estimating age of admixture in a cattle population based on SNP chip data

in Acta Agriculturae Slovenica (2012), 100(SUPPL.3), 115-119

The aim of this study was to predict individual age of admixture in the crossbred Swiss Fleckvieh population. We checked how well the method is dealing with recent admixture with high throughput single ... [more ▼]

The aim of this study was to predict individual age of admixture in the crossbred Swiss Fleckvieh population. We checked how well the method is dealing with recent admixture with high throughput single nucleotide polymorphism data from the bovine 50K SNP Chip. A total of 101 Red Holstein, 91 Simmental, and 308 crossed animals were available for analysis. Age of admixture was derived from the complete pedigree and molecular markers. The method applied (using SABER software) based on Markov-hidden Markov model was able to derive age of admixture similar to estimates of pedigree data, however the values were often overestimated. Of 21 investigated cases, results from SNP data reflected paternal and maternal age of admixture well for 9 cases but provided results out of range for the other 12 cases. Alternative methods based on breed-specific haplotype blocks need to be evaluated in the future. [less ▲]

Genetic variants in REC8, RNF212, and PRDM9 influence male recombination in cattle.

in PLoS Genetics (2012), 8(7), 1002854

We use >250,000 cross-over events identified in >10,000 bovine sperm cells to perform an extensive characterization of meiotic recombination in male cattle. We map Quantitative Trait Loci (QTL ... [more ▼]

We use >250,000 cross-over events identified in >10,000 bovine sperm cells to perform an extensive characterization of meiotic recombination in male cattle. We map Quantitative Trait Loci (QTL) influencing genome-wide recombination rate, genome-wide hotspot usage, and locus-specific recombination rate. We fine-map three QTL and present strong evidence that genetic variants in REC8 and RNF212 influence genome-wide recombination rate, while genetic variants in PRDM9 influence genome-wide hotspot usage. [less ▲]

Impact of sequencing design on missing marker imputation and genomic selection in cattle

Poster (2012)

Imputation of genotypes with low-density chips and its effect on reliability of direct genomic values in Dutch Holstein cattle.

in Journal of Dairy Science (2012), 95(2), 876-89

Genomic selection using 50,000 single nucleotide polymorphism (50k SNP) chips has been implemented in many dairy cattle breeding programs. Cheap, low-density chips make genotyping of a larger number of ... [more ▼]

Genomic selection using 50,000 single nucleotide polymorphism (50k SNP) chips has been implemented in many dairy cattle breeding programs. Cheap, low-density chips make genotyping of a larger number of animals cost effective. A commonly proposed strategy is to impute low-density genotypes up to 50,000 genotypes before predicting direct genomic values (DGV). The objectives of this study were to investigate the accuracy of imputation for animals genotyped with a low-density chip and to investigate the effect of imputation on reliability of DGV. Low-density chips contained 384, 3,000, or 6,000 SNP. The SNP were selected based either on the highest minor allele frequency in a bin or the middle SNP in a bin, and DAGPHASE, CHROMIBD, and multivariate BLUP were used for imputation. Genotypes of 9,378 animals were used, from which approximately 2,350 animals had deregressed proofs. Bayesian stochastic search variable selection was used for estimating SNP effects of the 50k chip. Imputation accuracies and imputation error rates were poor for low-density chips with 384 SNP. Imputation accuracies were higher with 3,000 and 6,000 SNP. Performance of DAGPHASE and CHROMIBD was very similar and much better than that of multivariate BLUP for both imputation accuracy and reliability of DGV. With 3,000 SNP and using CHROMIBD or DAGPHASE for imputation, 84 to 90% of the increase in DGV reliability using the 50k chip, compared with a pedigree index, was obtained. With multivariate BLUP, the increase in reliability was only 40%. With 384 SNP, the reliability of DGV was lower than for a pedigree index, whereas with 6,000 SNP, about 93% of the increase in reliability of DGV based on the 50k chip was obtained when using DAGPHASE for imputation. Using genotype probabilities to predict gene content increased imputation accuracy and the reliability of DGV and is therefore recommended for applications of imputation for genomic prediction. A deterministic equation was derived to predict accuracy of DGV based on imputation accuracy, which fitted closely with the observed relationship. The deterministic equation can be used to evaluate the effect of differences in imputation accuracy on accuracy and reliability of DGV. [less ▲]

A splice site mutation in the bovine RNF11 gene is responsible of growth retardation and increased susceptibility to inflammatory diseases.

Poster (2011, October 10)

Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature.

in Nature Genetics (2011), 43(5), 405-13

We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a approximately 780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits ... [more ▼]

We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a approximately 780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits linkage and linkage disequilibrium. We re-sequenced the interval in six sires with known QTL genotype and identified 13 clustered candidate quantitative trait nucleotides (QTNs) out of >9,572 discovered variants. We eliminated five candidate QTNs by studying the phenotypic effect of a recombinant haplotype identified in a breed diversity panel. We show that the QTL influences fetal expression of seven of the nine genes mapping to the approximately 780-kb interval. We further show that two of the eight candidate QTNs, mapping to the PLAG1-CHCHD7 intergenic region, influence bidirectional promoter strength and affect binding of nuclear factors. By performing expression QTL analyses, we identified a splice site variant in CHCHD7 and exploited this naturally occurring null allele to exclude CHCHD7 as single causative gene. [less ▲]