Wouter Coppieters

Wouter Coppieters
University of Liège | ulg · GIGA-Genomics Core Facility

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189
Publications
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Publications

Publications (189)
Article
Full-text available
The composition of the intestinal microbiome varies considerably between individuals and is correlated with health1. Understanding to what extend and how host genetics contributes to this variation is paramount yet has proven difficult as few associations have been replicated, particularly in humans2. We herein study the effect of host genotype on...
Article
Full-text available
Background Accurate haplotype reconstruction is required in many applications in quantitative and population genomics. Different phasing methods are available but their accuracy must be evaluated for samples with different properties (population structure, marker density, etc.). We herein took advantage of whole-genome sequence data available for a...
Article
The development of spots or lesions symptomatic of common scab on root and tuber crops is caused by few pathogenic Strep-tomyces with Streptomyces scabiei 87-22 as the model species. Thaxtomin phytotoxins are the primary virulence determinants, mainly acting by impairing cellulose synthesis, and their production in S. scabiei is in turn boosted by...
Preprint
Background Accurate haplotype reconstruction is required in many applications in quantitative and population genomics. Different phasing methods are available but their accuracy must be evaluated for samples with different properties (population structure, marker density, etc.). We herein took advantage of whole-genome sequence data available for a...
Conference Paper
Accurate haplotype reconstruction is required in many applications in animal genomics. In this study, we used deeply sequenced cattle genomes from a pedigree of 264 Holstein-Friesian individuals (mean coverage: 25.8X), mapped on the reference genome assembly ARS-UCD1.2. We selected 11,030,905 SNPs after the application of the Variant Quality Score...
Preprint
Full-text available
The development of spots or lesions symptomatic of the common scab disease on root and tuber crops is caused by few pathogenic Streptomyces with Streptomyces scabiei 87-22 as the model species. Thaxtomin phytotoxins are the primary virulence determinants, mainly acting by impairing cellulose synthesis, and their production in S . scabiei is in turn...
Article
Full-text available
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 di...
Preprint
Full-text available
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 di...
Article
Full-text available
Study Objectives Sleep disturbances and genetic variants have been identified as risk factors for Alzheimer’s disease. Our goal was to assess whether genome-wide polygenic risk scores (PRS) for AD associate with sleep phenotypes in young adults, decades before typical AD symptom onset. Methods We computed whole-genome Polygenic Risk Scores (PRS) f...
Preprint
Full-text available
We have generated a large heterogenous stock population by intercrossing eight divergent pig breeds for multiple generations. We have analyzed the composition of the intestinal microbiota at different ages and anatomical locations in > 1,000 6th- and 7th- generation animals. We show that, under conditions of exacerbated genetic yet controlled envir...
Article
Biological products of importance in food (f.i. milk) and medical (f.i. donor blood derived products) sciences often correspond to mixtures of samples contributed by multiple individuals. Identifying which individuals contributed to the mixture and in what proportions may be of interest in several circumstances. We herein present a method that allo...
Article
Full-text available
Colour‐sidedness is a striking coat colour pattern found in a number of cattle breeds, typically characterised by a white stripe that extends along the back, head and belly of the animal. This dominant phenotype is caused by two related translocations (Cs6 and Cs29) that alter a region downstream of the KIT gene. Gloucester cattle are native to the...
Preprint
Full-text available
Study Objectives Sleep disturbances and genetic variants have been identified as risk factors for Alzheimer’s disease. Our goal was to assess whether genome-wide polygenic risk scores (PRS) for AD associate with sleep phenotypes in young adults, decades before typical AD symptom onset. Methods We computed whole-genome Polygenic Risk Scores (PRS) f...
Article
Full-text available
Next generation sequencing (NGS) is a promising tool for analysing the quality and safety of food and feed products. The detection and identification of genetically modified organisms (GMOs) is complex, as the diversity of transgenic events and types of structural elements introduced in plants continue to increase. In this paper, we show how a stra...
Preprint
Biological products of importance in food (f.i. milk) and medical (f.i. donor blood derived products) sciences often correspond to mixtures of samples contributed by multiple individuals. Identifying which individuals contributed to the mixture and in what proportions may be of interest in several circumstances. We herein present a method that allo...
Article
Full-text available
Streptomyces lunaelactis MM109 T is a ferroverdin A (anticholesterol) producer isolated from cave moonmilk deposits. The complete genome sequence of MM109 T was obtained by combining Oxford Nanopore MinION and Illumina HiSeq and MiSeq technologies, revealing an 8.4-Mb linear chromosome and two plasmids, pSLUN1 (127,264 bp, linear) and pSLUN2 (46,82...
Article
Full-text available
Cave moonmilk deposits host an abundant and diverse actinobacterial population that has a great potential for producing novel natural bioactive compounds. In our previous attempt to isolate culturable moonmilk-dwelling Actinobacteria, only Streptomyces species were recovered, whereas a metagenetic study of the same deposits revealed a complex actin...
Article
Background & aims: A few rare monogenic primary immunodeficiencies (PID) are characterized by chronic intestinal inflammation that resembles Crohn's disease (CD). We investigated whether 23 genes associated with 10 of these monogenic disorders contain common, low-frequency or rare variants that increase risk for CD. Methods: Common and low frequ...
Conference Paper
Full-text available
To study the process of de novo mutation (dnm) in the bovine germ-line, we have sequenced the whole genomes of 743 dairy cattle constituting 131 sire-dam-offspring trios with an average of five grand-offspring each. A first study using five families revealed the common occurrence of somatic and germ-line mosaicism for dnms, pointing towards mutatio...
Article
Full-text available
We herein report the result of a large-scale, next generation sequencing (NGS)-based screen for embryonic lethal (EL) mutations in Belgian beef and New Zealand dairy cattle. We estimated by simulation that cattle might carry, on average, ∼0.5 recessive EL mutations. We mined exome sequence data from >600 animals, and identified 1377 stop-gain, 3139...
Article
Full-text available
We herein study genetic recombination in three cattle populations from France, New Zealand, and the Netherlands. We identify 2,395,177 crossover (CO) events in 94,516 male gametes, and 579,996 CO events in 25,332 female gametes. The average number of COs was found to be larger in males (23.3) than in females (21.4). The heritability of global recom...
Article
Full-text available
Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients...
Article
Full-text available
In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cau...
Article
Four newborn purebred Belgian Blue calves presenting a severe form of epidermolysis bullosa were recently referred to our heredo-surveillance platform. SNP array genotyping followed by autozygosity mapping located the causative gene in a 8.3-Mb interval on bovine chromosome 24. Combining information from (i) whole-genome sequencing of an affected c...
Conference Paper
Background/Purpose: Immune-mediated inflammatory disorders (IMIDs) share many genetic risk factors. Pleiotropy may exist at different levels and most of the underlying mechanisms are still to be uncovered. GWAS have identified hundreds of risk loci for IMIDs but causative genes have been identified in only a handful of cases. Recent fine-mapping ef...
Article
We herein describe the realization of a genome-wide association study for scrotal hernia and cryptorchidism in Norwegian and Belgian commercial pig populations. We have used the transmission disequilibrium test to avoid spurious associations due to population stratification. By doing so, we obtained genome-wide significant signals for both diseases...
Article
Full-text available
Cattle populations are characterized by regular outburst of genetic defects as a result of the extensive use of elite sires. The causative genes and mutations can nowadays be rapidly identified by means of genome-wide association studies combined with next generation DNA sequencing, provided that the causative mutations are conventional loss-of-fun...
Conference Paper
Full-text available
Background We aimed to investigate the 163 known loci and top SNP associated with inflammatory Bowel Disease (IBD) in a non- Caucasian Moroccan IBD cohort. Methods We genotyped 549 non- Caucasian Moroccan individuals with 285 IBD patients (211 Crohn's disease (CD), 63 Ulcerative colitis (UC) and 11 Indeterminate colitis (IC)) and 264 controls on cu...
Article
Full-text available
Background: Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. Methods: We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients...
Article
Full-text available
Background Belgian Blue cattle are famous for their exceptional muscular development or “double-muscling”. This defining feature emerged following the fixation of a loss-of-function variant in the myostatin gene in the eighties. Since then, sustained selection has further increased muscle mass of Belgian Blue animals to a comparable extent. In the...
Conference Paper
Full-text available
We herein report the results of a large-scale reverse genetic screen, based on next generation sequencing (NGS) of the exome or whole genome of more than 500 animals, to identify highly deleterious mutations that cause embryonic lethality in domestic cattle. We first demonstrate that -as in human -domestic cattle carry of the order of 100 loss-of-f...
Article
Full-text available
F4 enterotoxigenic Escherichia coli (F4 ETEC) are an important cause of diarrhea in neonatal and newly-weaned pigs. Based on the predicted differential O-glycosylation patterns of the 2 MUC13 variants (MUC13A and MUC13B) in F4ac ETEC susceptible and F4ac ETEC resistant pigs, the MUC13 gene was recently proposed as the causal gene for F4ac ETEC susc...
Conference Paper
Abstract Text: We herein report the results of a large-scale reverse genetic screen, based on next generation sequencing (NGS) of the exome or whole genome of more than 500 animals, to identify highly deleterious mutations that cause embryonic lethality in domestic cattle. We first demonstrate that - as in human - domestic cattle carry of the order...
Conference Paper
Full-text available
The host immune system plays an critical role in maintaining homeostasis with resident microbial communities, therefore ensuring that the complex symbiotic relationship is maintained. At the same time, resident microbiota contribute to host nutrition and energy balance and to the development or maintenance of a robust immune system. Dysbiosis of th...
Article
Full-text available
Chloride/proton exchange by the lysosomal anion transporter ClC-7/Ostm1 is of pivotal importance for the physiology of lysosomes and bone resorption. Mice lacking either ClC-7 or Ostm1 develop a lysosomal storage disease and mutations in either protein have been found to underlie osteopetrosis in mice and humans. Some human disease-causing CLCN7 mu...
Article
Full-text available
The aim of this study was to determine a genetic basis for IgA concentration in milk of Bos taurus. We used a Holstein-Friesian x Jersey F2 crossbred pedigree to undertake a genome-wide search for QTL influencing IgA concentration and yield in colostrum and milk. We identified a single genome-wide significant QTL on chromosome 16, maximising at 4.8...
Data
Genome-wide scan for QTL affecting IgA, IgG and IgM. Manhattan plots obtained using a haplotype-based mixed model that simultaneously extracts linkage and LD information and corrects for stratification. For antibody (IgA, IgG or IgM as indicated) concentration (left column) and yield (right column) in 2nd colostrum, 8th colostrum or mid-lactation m...
Data
Sequence variant data for the six F1 sires. Sires are numbered 1001–1006. Sequence variant information is given in terms of reference allele and alternative allele, as well as reference amino acid and alternative amino acid where applicable. (XLS)
Data
Phenotype data used for QTL mapping. ID = unique animal identification number. Cohort = cohort 1 or 2, based on year of birth. Phenotypes listed are milk volume, IgA concentration, IgA yield, IgG concentration, and IgG yield for the second and eighth milkings, IgA concentration and yield at mid-lactation, PIGR mRNA expression in liver and fat tissu...
Data
Genotypes in the PIGR region. ID = unique animal ID. Genotypes are listed as 1 or 2 for both the paternal and maternal alleles. (XLS)
Data
Marker map information. For the markers listed in Table S2, the bovine chromosome 16 map position (UMD3.1) is given, along with RS# if available. (XLS)
Article
Full-text available
Leigh syndrome is an early onset, often fatal progressive neurodegenerative disorder caused by mutations in the mitochondrial or nuclear DNA. Until now, mutations in more than 35 genes have been reported to cause Leigh syndrome, indicating an extreme genetic heterogeneity for this disorder, but still only explaining part of the cases. The possibili...
Article
Full-text available
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 d...
Data
Full-text available
Effects on fertility of the FANCI deletion. Pregnancy failure rate detected as 100% minus non return into oestrus (NR) at 56, 90 and 270 days post-insemination in the four possible matings. The genotype probabilities of the dams are estimated from the knowledge of the genotype of their sire combined with the known frequency of the BS mutation in th...
Data
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Primer pairs to validate the deletion in the FANCI gene. (PDF)
Data
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Targeted and genome-wide resequencing of BS cases and controls. (A) Distribution of the genomic distance separating random mate-pairs and mate-pairs flanking the BS deletion. (B) IGV screen captures of mate-pair reads mapping to the BTA21 20,536,086–20,541,232 chromosome interval for three unaffected controls (lanes 1–3) and a BS calve (lane 4), as...
Data
(A) Black dots correspond to the total number of CO events identified in the paternal genome of 10,192 GIII sons sorted by GII sire. The red dots mark the average GRR for each GII sire. GRR did not differ significantly between Holstein-Friesian and Jersey bulls. (B) Correlation between the GRR estimated for 72 GII sires separately from the number o...
Data
(A) Linear relationship between chromosome length in Mb (from UMD3.0 build) and average number of CO-events for the 29 bovine autosomes. The least square regression is characterized by a Y-intercept = 0.48 and a slope = 0.07CO/10 Mb. The slope of the regression is intermediate between the slopes characterizing male and female recombination in human...
Data
Position of the amplicons used to scan the REC8 (A), and RNF212 genes (B) (cfr. Table S2). The corresponding RNF212 gene model has been submitted to Genbank. (PPTX)
Data
(A) Following Kong et al. [8], we tested the effect of base pair composition and gene content on LRR by multiple regression. As in human, local recombination rate was positively correlated with CpG content, yet negatively correlated with GC, polyA/polyT and gene content (after adjustment for CpG content). CpG content accounted for ∼19% of the varia...
Data
(A) Representative example of the variation in male recombination in 60-Kb windows across a bovine autosome (BTA14). The plain black like (upper halve) corresponds to recombination rate estimated in the Dutch population, while the dotted black line (lower halve) corresponds to the recombination rate estimated in the NZ population. The red and blue...
Data
(A) Black dots: Average overlap (0 to 1) between marker intervals (<800-Kb) with assigned CO events and “hot" 60-K windows for GIII-sons sorted by GII-sire. Red dots: Average overlap for all CO events transmitted by corresponding GII-sire. (B) Correlation between average hot-window usage estimated for the 72 shared GII-sires respectively from gamet...
Data
(A) GIII sons inherit chromosomes with 0, 1, 2, 3, … CO from their GII sires. In this analysis, we only use “di-CO" chromosomes (i.e. with 2 CO). We measure the distance between CO-pairs in centimorgan (GIL-cM) or in base-pairs (GIL-bp) prior to normalization (i.e. expressed in standard deviations from the chromosome mean). Thus, the distance betwe...
Data
Full-text available
(A) For each of the 29 bovine autosomes (BTA1-29), column I: frequency distribution of gametes with 0, 1, 2, … CO-events expected in the absence of cross-over interference (blue), expected given the value of ν maximizing the likelihood of the overall data (light red), expected given the value of given the value of ν maximizing the likelihood of the...
Data
Primers used for amplification and resesequencing of candidate genes REC8, RNF212, KCNJ2, KCNJ16 and gonosomal PRDM9-XA and -XB. (XLS)
Data
Primer and probes used for genotyping candidate QTN using 5′exonculease (Taqsman) assays. (XLS)
Article
Mastitis remains the most important health issue in dairy cattle. Improved methods to identify cows developing subclinical mastitis would benefit farmers. We herein describe a novel method to determine the somatic cell counts (SCC) of individual cows by bulk genotyping a sample of milk from the milk tank with panels of genome-wide single nucleotide...
Article
Full-text available
Author Summary Homologous recombination is an essential cellular process that determines proper chromosome segregation during meiosis, affects fertility, and influences evolvability. Nevertheless, the components of the recombination apparatus remain incompletely characterized in mammals. One approach to identify such components is to identify the g...