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Genome and environment together greatly influence how an organism develops and functions. Cattle is a livestock species with high economic significance; thus, deciphering how its genome and genomic information relates to its phenotype is crucial. Nevertheless, our understanding of bovine genomes is incomplete: investigation of bovine genomes thus far has mainly focused on single-nucleotide variants, leaving less tractable and complex variants, such as structural variants, underexplored. In this thesis, I present a comprehensive and in-depth investigation of structural variants in bovine genomes. Two structural variant catalogues, generated from genotyping data and deeply sequenced bovine genomes, revealed ~32 and ~5,000 SVs per genome, respectively. Furthermore, I integrated statistical associations and ~omics data, and delineated a 12-Kb copy number variant (CNV) as the likely causal variant of a major clinical mastitis QTL. This CNV encompasses an enhancer that targets the group-specific component gene, which encodes a vitamin D binding protein. Lastly, I investigated the emergence of de novo structural variants by exploiting 127 multi-generational deeply sequenced genomes. The pedigree-based germline mutation rate corresponded to one de novo structural variant per 8.5 births. The de novo structural variants were strongly biased towards male germlines and in vitro produced animals, unravelling sex and reproductive technology effects. Together, this thesis highlights a broad spectrum of bovine structural variants: from extremely rare de novo mutations to population variants, highlighting one that exerts strong effects on economically important traits. This thesis contributes to advancing our understanding of bovine structural variation.

The growth of animals is a complex trait, in chicken resulting in a diverse variety of forms, caused by a heterogeneous genetic basis. Bantam chicken, known as an exquisite form of dwarfism, has been used for crossbreeding to create corresponding dwarf counterparts for native fowls in the Dutch populations. Here, we demonstrate the heterogeneity of the bantam trait in Dutch chickens and reveal the underlying genetic causes, using whole‐genome sequence data from matching pairs of bantam and normal‐sized breeds. During the bantam‐oriented crossbreeding, various bantam origins were used to introduce the bantam phenotype, and three major bantam sources were identified and clustered. The genome‐wide association studies revealed multiple genetic variants and genes associated with bantam phenotype, including HMGA2 and PRDM16, genes involved in body growth and stature. The comparison of associated variants among studies illustrated differences related to divergent bantam origins, suggesting a clear heterogeneity among bantam breeds. We show that in neo‐bantam breeds, the bantam‐related regions underwent a strong haplotype introgression from the bantam source, outcompeting haplotypes from the normal‐sized counterpart. The bantam heterogeneity is further confirmed by the presence of multiple haplotypes comprising associated alleles, which suggests the selection of the bantam phenotype is likely subject to a convergent direction across populations. Our study demonstrates that the diverse history of human‐mediated crossbreeding has contributed to the complexity and heterogeneity of the bantam phenotype.

Genetic diversity is the foundation for selection to act upon a population: without diversity, evolution can not occur and species can not adapt to changing environments. In this thesis, I provide an in-depth analysis of the genome-wide patterns of diversity in local chicken breeds of small effective population size. Since their domestication in Southeast Asia around 9,500 years ago, domestic chickens have undergone human-driven selection resulting in the creation of hundreds of breeds, each described by a precise set of morphological features. Domesticated chicken breeds are therefore an excellent study system to investigate the effects of demography on genomic variation. Using a combination of the latest genomics tools, I show that, besides signs of recent inbreeding and declined diversity, changes in breeding preferences generated novel and identifiable variation. Interestingly, the genetic basis of some of this variation has evolved in other bird species through parallel evolution despite their divergence from chicken millions of years ago. However, as I emphasize, the outstanding diversity harboured by local chicken breeds can only be preserved in the near future if conservation programmes become genomics-informed. The rationale is the ability of genomic data to provide additional infor- mation on the functional relevance of such variation, which has important implications for conservation. Therefore, by means of genomic data, we can better control for deleterious alleles, while increasing genetic diversity. The identification of functionally important mutations have for a long time been limited to protein-coding genes. In this thesis, I demonstrate through the development of the ch(icken)CADD model that sub regions within conserved non-coding elements also harbour variants with a negative fitness effect, as their association with known disease genes in other vertebrate species demonstrate. Overall, the findings of this thesis show that genetic diversity should

Land animal domestication has typically led to remarkable phenotypic diversity, stemming from a broad genetic background. The process of land animal domestication turns out to be a complex, long-term event with extensive gene-flow between wild and captive populations. Using pig as model, this chapter provides an in-depth overview of domestication-related events leading towards the genetic diversity in extant pig breeds. Five events in the evolutionary history and domestication of pigs can be recognized that are important for the genetic variation in modern pig genomes: (1) Speciation of Sus species in Island South-East Asia (ISEA); (2) Divergence between European and Asian lineages; (3) Independent domestication leading to separate domesticated clades in Europe and Asia; (4) Hybridization between domesticated pigs from Asia and Europe; and (5) Breed formation. Remarkably, the extensive mixture of genetic material leading towards the current European commercial pigs has resulted in domestic breeds that are genetically more diverse than their wild ancestors. Nowadays, commercial breeding and genomics go hand in hand. Genomics has not only proven useful to provide understanding about the domestication history of pigs but also about the molecular mechanisms underlying traits of interest. Moreover, genomic selection is an important tool integral to modern commercial breeding.

The divergence between indicine cattle (Bos indicus) and taurine cattle (Bos taurus) is estimated to have occurred approximately 250,000 years ago, but a small number of European cattle breeds still display shared ancestry with indicine cattle. Additionally, following the divergence of African and European taurine, the gene flow between African taurine and southern European cattle has also been proposed. However, the extent to which non-European cattle ancestry is diffused across southern European cattle has not been investigated thoroughly. Also, in recent times, many local breeds have suffered severe reductions in effective population size. Therefore, in the present study, we investigated the pattern of genetic diversity in various European cattle based on single nucleotide polymorphisms (SNP) identified from whole-genome sequencing data. Additionally, we also employed unlinked and phased SNP-based approaches on high-density SNP array data to characterize non-European cattle ancestry in several southern European cattle breeds. Using heterozygosity-based parameters, we concluded that, on average, nucleotide diversity is greater in southern European cattle than western European (British and commercial) cattle. However, an abundance of long runs of homozygosity (ROH) and the pattern of Linkage disequilibrium decay suggested recent bottlenecks in Maltese and Romagnola. High nucleotide diversity outside ROH indicated a highly diverse founder population for southern European and African taurine. We also show that Iberian cattle display shared ancestry with African cattle. Furthermore, we show that Podolica is an ancient cross-bred between Indicine zebu and European taurine. Additionally, we also inferred similar ancestry profile of non-European cattle ancestry in different Balkan and Italian cattle breeds which might be an indication of the common origin of indicine ancestry in these breeds. Finally, we discuss several plausible demographic scenarios which might ac

Understanding variation in genome structure is essential to understand phenotypic differences within populations and the evolutionary history of species. A promising form of this structural variation is copy number variation (CNV). CNVs can be generated by different recombination mechanisms, such as non-allelic homologous recombination, that rely on specific characteristics of the genome architecture. These structural variants can therefore be more abundant at particular genes ultimately leading to variation in phenotypes under selection. Detailed characterization of CNVs therefore can reveal evolutionary footprints of selection and provide insight in their contribution to phenotypic variation in wild populations.

The great tit is a widely studied passerine bird species in ecology that, in the past decades, has provided important insights into speciation, phenology, behavior and microevolution. After completion of the great tit genome sequence, a customized high density 650k SNP array was developed enabling more detailed genomic studies in this species.

Traditional Dutch chicken breeds are marginalised breeds of ornamental and cultural-historical importance. In the last decades, miniaturising of existing breeds (so called neo-bantam) has become popular and resulted in alternatives to original large breeds. However, while backcrossing is increasing the neo-bantams homozygosity, genetic exchange between breeders may increase their genetic diversity. We use the 60K SNP array to characterise the genetic diversity, demographic history, and level of inbreeding of Dutch heritage breeds, and particularly of neo-bantams. Commercial white layers are used to contrast the impact of management strategy on genetic diversity and demography. A high proportion of alleles was found to be shared between large fowls and neo-bantams, suggesting gene flow during neo-bantams development. Population admixture analysis supports these findings, in addition to revealing introgression from neo-bantams of the same breed and of phenotypically similar breeds. The prevalence of long runs of homozygosity (ROH) confirms the importance of recent inbreeding. A high diversity in management, carried out in small breeding units explains the high heterogeneity in diversity and ROH profile displayed by traditional breeds compared to commercial lines. Population bottlenecks may explain the long ROHs in large fowls, while repetitive backcrossing for phenotype selection may account for them in neo-bantams. Our results highlight the importance of using markers to inform breeding programmes on potentially harmful homozygosity to prevent loss of genetic diversity. We conclude that bantamisation has generated unique and identifiable genetic diversity. However, this diversity can only be preserved in the near future through structured breeding programmes.

Investigate the genetic make-up of nine horse populations in the Netherlands: increase our understanding of their evolutionary history and provide valuable information on how to best conserve or improve these populations

Plant domestication was a pivotal accomplishment in human history, but also led to a reduction in genetic diversity of crop species compared to their wild ancestors. How this reduced genetic diversity affected plant–microbe interactions belowground is largely unknown. Here, we investigated the genetic relatedness, root phenotypic traits and rhizobacterial community composition of modern and wild accessions of common bean (Phaseolus vulgaris) grown in agricultural soil from the highlands of Colombia, one of the centers of common bean diversification. Diversity Array Technology-based genotyping and phenotyping of local common bean accessions showed significant genetic and root architectural differences between wild and modern accessions, with a higher specific root length for the wild accessions. Canonical Correspondence Analysis indicated that the divergence in rhizobacterial community composition between wild and modern bean accessions is associated with differences in specific root length. Along the bean genotypic trajectory, going from wild to modern, we observed a gradual decrease in relative abundance of Bacteroidetes, mainly Chitinophagaceae and Cytophagaceae, and an increase in relative abundance of Actinobacteria and Proteobacteria, in particular Nocardioidaceae and Rhizobiaceae, respectively. Collectively, these results establish a link between common bean domestication, specific root morphological traits and rhizobacterial community assembly.

This study is part of the FAANG project., "This study is part of the FAANG project, promoting rapid prepublication of data to support the research community. These data are released under Fort Lauderdale principles, as confirmed in the Toronto Statement (Toronto International Data Release Workshop. Birney et al. 2009. Pre-publication data sharing. Nature 461:168-170). Any use of this dataset must abide by the FAANG data sharing principles. Data producers reserve the right to make the first publication of a global analysis of this data. If you are unsure if you are allowed to publish on this dataset, please contact faang@iastate.edu to enquire. The full guidelines can be found at http://www.faang.org/data-share-principle”

We used extensive data from a long-term study of great tits (Parus major) in the United Kingdom and Netherlands to better understand how genetic signatures of selection translate into variation in fitness and phenotypes. We found that genomic regions under differential selection contained candidate genes for bill morphology and used genetic architecture analyses to confirm that these genes, especially the collagen gene COL4A5, explained variation in bill length. COL4A5 variation was associated with reproductive success, which, combined with spatiotemporal patterns of bill length, suggested ongoing selection for longer bills in the United Kingdom. Last, bill length and COL4A5 variation were associated with usage of feeders, suggesting that longer bills may have evolved in the United Kingdom as a response to supplementary feeding.

Contains fulltext : 159994.pdf (publisher's version ) (Open Access), Background: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1,5mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20min of a 40min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. TDCS was delivered for 20min before patients performed a 20min lasting visual vigilance task. Results: Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in reaction time associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Conclusions: Anodal tDCS over the right parietal cortex can counteract the increase in reaction times during vigilance performance but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

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cum laude graduation