Biology subjects

Groenen, M.

Publications and source records attributed to Groenen, M..

9 recordsLinked to original sources

bioRxiv2026

Source of genome-wide deleterious variation in a global cattle cohort

Background Identifying deleterious DNA changes underpins efforts to improve animal health, welfare, and sustainable breeding. In cattle, current variant prioritization focuses on coding changes, uses single annotation types, and gives limited resolution in non-coding sequence. Results We developed BovCADD (bovine Combined Annotation-Dependent Depletion), a nucleotide-level deleteriousness score for substitutions in Bos taurus and Bos indicus, combining evolutionary constraint, sequence context, epigenetic and regulatory annotations, and gene and protein features. A logistic regression model trained on 41.9 million high-frequency derived alleles from about 3,700 cattle, contrasted with context-matched simulated variants, scored all 8.1 billion possible substitutions. BovCADD distinguished known pathogenic variants from background variation, discriminated among variants within the same consequence class, and scored intronic and intergenic sites. Aggregating scores identified genes carrying rare deleterious variation and revealed elevated genetic load at trait-relevant loci and in bottlenecked, intensively selected populations. Conclusions BovCADD provides the first genome-wide, nucleotide-resolution measure of deleteriousness in cattle, extending variant interpretation to non-coding sequences and linking variant-level prioritization to population-level patterns of mutational burden. Precomputed scores for all substitutions are publicly available.

genomics↗

bioRxiv2025

Genomic and morphometric evidence for Austronesian-mediated pig translocation in the Pacific

Human mediated translocation of non-native pig species (genus Sus) to the islands of Wallacea and Oceania has significantly altered local ecosystems. To investigate the timing and trajectory of these introductions, we conducted both genomic analyses of 576 pig nuclear genomes and a geometric morphometric analysis of 714 modern and ancient dental remains. Our analyses demonstrate that feral and domestic pigs in Wallacea and Oceania possess diverse ancestries resulting from the introduction of multiple, sequential pig populations followed by gene flow. Despite the variability in their genomic ancestry these pigs all possess a distinct tooth morphology, and a genetic link to the Chinese domestic pig populations that accompanied the dispersal of Austronesian language speakers [~]4,000-3,000 years ago via Taiwan and the Philippines.

evolutionary biology↗

bioRxiv2025

Mapping the Landscape of Allele-Specific Expression In Porcine Genomes

Allele-specific expression (ASE) is the imbalanced expression of two alleles of the same locus. It is quite pervasive among mammals and is associated with healthy and economically relevant traits. ASE is often used to support the identification of variants related to gene expression (cis-eQTLs). Thus, profiling ASE represents a significant step in elucidating the mechanism underlying gene expression regulation. In this study, we developed an ASE pipeline using public available RNA-seq data and open-source software. Using this pipeline, we were able to profile pervasive allelic imbalance across 42 tissues and 34 breeds from the Farm-GTEX-pig consortium at both SNP and gene levels without the need for parental genotype or whole genome sequence data. ASE was widely, but not evenly, spread across the genome. We also observed considerable variation in ASE profiles among various tissues, in which the ASE fraction ranged from 1.3% to 54.1%. ASE tends to be highly tissue-specific, and the overlap across tissues is limited. The functional analysis of tissue-specific ASE sites indicates that they are involved in the critical maintenance of these tissues. Our ASE pipeline can be readily applied to other RNA-seq data sets for livestock, thereby significantly expanding its potential utility. The wealth of available ASE resources provides a solid foundation for identifying regulatory elements within the genome that drive complex traits in livestock, making our pipeline and results valuable resources for researchers in this field.

genomics↗

bioRxiv2025

Genomic Insights into the Demographic History and Local Adaptation of Wild Boars Across Eurasia

Wild boars exhibit genetic and phenotypic diversity shaped by migrations and local adaptations. Its expansion across Eurasia, especially in central Asia, remains underexplored. Here, we present newly sequenced whole-genome data of 47 wild boars from Eastern Asia, Central Asia, and Europe, combined with 49 existing genomes, creating a comprehensive dataset of 96 individuals. Our analyses show that Asian wild boars and Southeast Asian Suids split [~]3.6 Mya, with Central Asian and Southern Chinese ancestors diverging [~]1.8 Mya. The split between Central Asian and European-Near East ancestors occurred [~]0.9 Mya, followed by a European-Near East divergence [~]0.6 Mya. We identify signatures of local adaptation in Central Asian populations, including two positively selected variants in LPIN1, associated with cold adaptation, and a missense mutation in ALPK2, linked to meat traits. These findings provide insights into wild boar dispersal and adaptation, and shed light on domestic pigs breeding.

evolutionary biology↗

bioRxiv2024

A generic pipeline for CADD score generation: chickenCADD and turkeyCADD

Combined Annotation Dependent Depletion (CADD) is a machine learning approach used to predict the deleteriousness of genetic variants across a genome. By integrating diverse genomic features, CADD assigns a PHRED-like rank score to each potential variant. Unlike other methods, CADD does not rely on limited datasets of known pathogenic or benign variants but uses larger and less biased training sets. The rapid increase in high-quality genomes and functional annotations across species highlights the need for an automated, non-species-specific pipeline to generate CADD scores. Here, we introduce such a pipeline, facilitating the generation of CADD scores for various species using only a high-quality genome with gene annotation and a multi-species alignment. Additionally, we present updated chickenCADD scores and newly generated turkeyCADD scores, both generated with the pipeline.

genomics↗

bioRxiv2024

Genomic prediction in insects: a case study on wing morphology traits in the jewel wasp Nasonia vitripennis

BackgroundBiological control is a sustainable strategy to combat agricultural pests. Yet, due to legislation, importing non-native biocontrol agents is increasingly restricted. Thus, selective breeding of biocontrol traits of native species is suggested to enhance performance of existing biocontrol agents. Genomic prediction is a new alternative to exploit genetic variation for improving biocontrol efficacy. This study aims to establish proof-of-principle for genomic prediction in insect biocontrol agents, using wing morphology traits in the parasitoid Nasonia vitripennis Walker (Pteromalidae) as a model. MethodsWe performed genomic prediction using a Genomic Best Linear Unbiased Prediction (GBLUP) model, using a total of 1,230 individuals with 8,639 SNPs generated by genotyping-by-sequencing (GBS). We used individuals from two generations from the outbred HVRx population, 717 individuals from generation G169 and 513 from generation G172. To assess genomic prediction accuracy, we used across- generation validation: forward validation for G172 from G169, backward in time validation for G169 from G172, and also 5-fold cross-validation, randomly using one fifth of the population as validiation and the others as training groups. ResultsFor size-related traits, including tibia length, wing length, width, and second moment wing area, the accuracy of genomic prediction was close to zero in both across-generation validations, but much higher in 5-fold cross-validation (ranging 0.54-0.68). For the shape-related trait wing aspect ratio, a high accuracy was found for all three validation strategies, with 0.47 for across-generation forward validation, 0.65 for across-generation backward validation, and 0.54 for 5-fold cross-validation. ConclusionPromising accuracies were observed for all traits in 5-fold cross-validation, but not in the across-generation validations. Overall, applying genomic selection in insect biocontrol agents with a relative small effective population size seems promising. However, factors such as the biology of insects, the techniques of phenotyping, and costs of large-scale genotyping still challenge the application of genomic selection to biocontrol agents.

genetics↗

bioRxiv2023

Multi-omics analysis reveals signatures of selection and loci associated with complex traits in pigs

Selection signatures that contribute to phenotypic diversity, especially morphogenesis in pigs, remain to be further elucidated. To reveal the regulatory role of genetic variations in phenotypic differences between Eastern and Western pig breeds, we performed a systematic analysis based on seven high-quality de novo assembled genomes, 1,081 resequencing data representing 78 domestic breeds, 162 methylomes, and 162 transcriptomes of skeletal muscle from Tongcheng (Eastern) and Landrace (Western) pigs at 27 developmental stages. Selective sweep uncovers different genetic architectures behind divergent selection directions for the Eastern and Western breeds. Notably, two loci showed functional alterations by almost fixed missense mutations. By integrating time-course transcriptome and methylome, we revealed differences in developmental timing during myogenesis between Eastern and Western breeds. Genetic variants under artificial selection have critical regulatory effects on progression patterns of heterochronic genes like GHSR and BDH1, by the interaction of local DNA methylation status, particularly during embryonic development. Altogether, our work not only provides valuable resources for understanding pig complex traits, but also contributes to human biomedical research.

genomics↗

bioRxiv2021

A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle

Clinical mastitis (CM) is an inflammatory disease occurring in the mammary glands of lactating cows. CM is under genetic control, and a prominent CM resistance QTL located on chromosome 6 was reported in various dairy cattle breeds. Nevertheless, the biological mechanism underpinning this QTL has been lacking. Herein, we mapped, fine-mapped, and discovered the putative causal variant underlying this CM resistance QTL in the Dutch dairy cattle population. We identified a ~12 kb multi-allelic copy number variant (CNV), that is in perfect linkage disequilibrium with a GWAS lead SNP, as a promising candidate variant. By implementing a genome-wide association study (GWAS) and through expression QTL mapping, we showed that the group-specific component gene (GC), a gene encoding a vitamin D binding protein, is an excellent candidate causal gene for the QTL. The multiplicated alleles are associated with increased GC expression and low CM resistance. Ample evidence from functional genomics data supports the presence of an enhancer within this CNV, which would exert cis-regulatory effect on GC. We observed that strong positive selection swept the region near the CNV, and haplotypes associated with the multiplicated allele were strongly selected for. Moreover, the multiplicated allele showed pleiotropic effects for increased milk yield and reduced fertility, hinting that a shared underlying biology for these effects may revolve around the vitamin D pathway. These findings together suggest a putative causal variant of a CM resistance QTL, where a cis-regulatory element located within a CNV can alter gene expression and affect multiple economically important traits. Author summaryClinical mastitis (CM) is an inflammatory disease that negatively influences dairy production and compromises animal welfare. Although one major genetic locus for CM resistance was mapped on bovine chromosome 6, a mechanistic description of this association has been lacking. Herein, we report a 12-kb multiallelic copy number variant (CNV), encompassing a strong enhancer for group-specific component gene (GC), as a likely causal variant for this locus. This CNV is associated with high GC expression and low CM resistance. We speculate that upregulation of GC leads to a large amount of vitamin D binding protein, which in turn, reduces biologically available vitamin D, resulting in vitamin D deficiency and low CM resistance. Despite the negative effect on CM resistance, the CNV contributes to increased milk production, hinting at balancing selection. Our results highlight how multiplication of a regulatory element can shape economically important traits in dairy cattle, both in favourable and unfavourable directions.

genomics↗

bioRxiv2020

Evolutionarily conserved non-protein-coding regions in the chicken genome harbor functionally important variation

The availability of genomes for many species has advanced our understanding of the non-protein-coding fraction of the genome. Comparative genomics has proven to be an invaluable approach for the systematic, genome-wide identification of conserved non-protein-coding elements (CNEs). However, for many non-mammalian model species, including chicken, our capability to interpret the functional importance of variants overlapping CNEs has been limited by current genomic annotations, which rely on a single information type (e.g. conservation). We here studied CNEs in chicken using a combination of population genomics and comparative genomics. To investigate the functional importance of variants found in CNEs we develop a ch(icken) Combined Annotation-Dependent Depletion (chCADD), a variant effect prediction tool first introduced for humans and later on for mouse and pig. We show that 73 Mb of the chicken genome has been conserved across more than 280 million years of vertebrate evolution. The vast majority of the conserved elements are in non-protein-coding regions, which display SNP densities and allele frequency distributions characteristic of genomic regions constrained by purifying selection. By annotating SNPs with the chCADD score we are able to pinpoint specific subregions of the CNEs to be of higher functional importance, as supported by SNPs found in these subregions are associated with known disease genes in humans, mice, and rats. Taken together, our findings indicate that CNEs harbor variants of functional significance that should be object of further investigation along with protein-coding mutations. We therefore anticipate chCADD to be of great use to the scientific community and breeding companies in future functional studies in chicken.

genomics↗