Adaptiv musik gör det möjligt för spelutvecklare att implementera musik som reagerar på andra spel-parametrar. Därmed kan musiken följa spelets narrativ i realtid och på så vis bidra till en uppslukande upplevelse. I ett spel med adaptiv musik innehar spelaren agens och inverkan på musiken, samtidigt som musiken också innehar agens och inverkan på spelaren. Vi har i detta kandidatarbete undersökt hur den adaptiva musiken skulle kunna påverka spelarens prestationsförmåga genom att titta på element som kan ha inflytande i den här frågan, till exempel musikens funktioner och stress. Vi har bedrivit tester samt kombinerat kvantitativa och kvalitativa metoder för att både kunna fördjupa oss i frågan och gå in på detaljerna, men samtidigt erhålla bredare och mer övergripande kunskap om den adaptiva musikens roll i spel. I texten skildrar vi det praktiska arbetet med alla dess tekniska ingredienser som vi utförde för att skapa och implementera adaptiv musik i spel. Vi erbjuder avslutningsvis även en redogörelse av den insamlade datan, en metodiskt utförd analys, samt en djupgående diskussion som reflekterar över arbetet och föreslår hur man skulle kunna fortsätta undersöka detta ämne. / Adaptive music allows game developers to implement music that responds to other game parameters. Thus, the music can follow the game's narrative in real time, thereby contributing to an immersive experience. In a game with adaptive music, the player has agency and influence on the music, while at the same time the music also has agency and influence on the player. In this bachelor thesis, we have investigated how adaptive music could affect player performance by looking at elements that may influence this issue, such as music features and stress. We have conducted tests as well as combined quantitative with qualitative methods which enabled us to dive deeper in this question and get into the details, while at the same time obtaining broader and more comprehensive knowledge about the role of adaptive music in games. In the text, we describe the practical work with all of  it’s technical ingredients that we performed to create and implement adaptive music in a game. Finally, we also provide an account of the collected data, a methodically conducted analysis, and an in-depth discussion that reflects on the work and suggests how to continue researching this subject.

Chicken is a major protein source and intensively selected for economically important traits by humans. As such, this generated a huge range of phenotypes that representing a diverse spectrum of genetic variation. Understanding the functional basis of the genetic variants that underlie these traits, however, remains a formidable endeavour particularly for complex traits. Nonetheless, molecular phenotyping of an organism from sequenced data is doable with the advances in bioinformatics analysis and unparalleled surveys of genome wide genetic variants. This provides the opportunity to gain insights into the genome architecture and assists in identifying chromosomal regions underlying selection through a “sequences to consequences” approach. Combining a whole genome re-sequencing (WGS) approach with the knowledge of selection history, this thesis aimed to study the chromosomal regions and genetic variants underlying traits of interest in various selected chicken populations. To achieve this, genetic (quantitative and population genetics), genomic and bioinformatics approaches were employed and integrated to investigate the genome wide selection signatures in a number of different lines of chicken selected for different complex traits. This includes analysing: (i) divergently selected broilers for fatness traits (Chapter 2), (ii) a closed population of layer chickens (Chapter 3), (iii) selection signatures unique to broiler or layer chickens (Chapter 4) and (iv) selection signatures in colony stimulating factor 1 (CSF1) associated with gene expression differences in broiler and layer populations (Chapter 5). Candidate genes and nucleotides underlying potential selection regions were identified, and attempts were made to further elucidate the potential interplay between genes and the biological pathways involved in regulating traits in these selected chicken lines. Incorporating integrative approaches, variants within selection signatures were annotated to provide further evidence of their functional consequences. Overall, non-coding regions were enriched in selection signatures implied that causative variants may have regulatory roles. Capitalising on the millions of genetic variants discovered from WGS, chromosomal regions subject to selection were detected using a number of population genetics statistics. In broiler chicken lines divergently selected for very low-density plasma lipoprotein (VLDL) (Chapter 2), incorporating signatures of selection helped to improve the resolution of previously mapped quantitative traits loci (QTL) intervals. This research demonstrated that the integration of the analysis of selection signatures with functional annotation of genetic variants enabled refinement and characterisation of the QTL for fatness traits. In a closed population of brown leghorn layers (Chapter 3), evidence of selection signatures was found through Tajima’s D analysis. The analysis unravelled selection signatures encoding genes involved in numerous pathways and genes having key roles such as in behaviour, including feather pecking. Combining population differentiation statistic (FST) and Tajima’s D, a number of regions subject to divergent selection between broilers and white egg layers were identified (Chapter 4). Selection signatures were found to harbour mutations involved in cellular and tissue development, including genes having important roles in growth, fatness, egg shell strength and muscle development. These regions and the overlapping genes thereby may be potentially contributing to the different phenotypic variations observed between broilers and layers. In Chapter 5, a revised gene model for colony stimulating factor 1 (CSF1) showing complex pattern of alternate transcripts was predicted from transcriptome analysis of RNA isolated from 21 different tissues. In parallel, selection signatures analysis with the FST statistic, identified selection signatures that differentiate broilers to white egg layers (3 regions) or brown egg layers to white egg layers (4 regions). All these selection signatures were located within non-coding regions, indicating potential divergent selection of CSF1 within regulatory regions. Overall, the results presented in this thesis using the “sequences to consequences” approach, link several genomic regions and genes to phenotypic variation in domesticated chicken lines. The work reported here serves as a foundation for further study to decipher the relationship between “genotype and phenotype” and its functional consequences due to selection.

Amaranthus hypochondriacus is an emerging pseudo-cereal native to the New World which has garnered increased attention in recent years due to its nutritional quality, in particular its seed protein, and more specifically its high levels of the essential amino acid lysine. It belongs to the Amaranthaceae family, is an ancient paleotetraploid that shows amphidiploid inheritance (2n=32), and has an estimated genome size of 466 Mb. Here we present a high-quality draft genome sequence of the grain amaranth A. hypochondriacus. The genome assembly consisted of 377 Mb in 3,518 scaffolds with an N50 of 371 kb. Repetitive element analysis predicted that 48% of the genome is comprised of repeat sequences, of which Copia-like elements were the most common classified retrotransposon. A transcriptome, consisting of 66,370 contigs, was assembled from eight different tissue and abiotic stress libraries. Annotation of the genome identified 23,059 genes that were supported by our de novo transcriptome assembly, the RefBeet 1.1 gene index and the Uniprot_sprot database. To describe the genetic diversity within the grain amaranths (A. hypochondriacus, A. caudatus, and A. cruentus) and their putative progenitor (A. hybridus) we re-sequenced seven accessions in the genus Amaranthus (four A. hypochondriacus, and one of each A. caudatus, A. cruentus, and A. hybridus), which identified 7,184,636 and 1,760,433 interspecific and intraspecific single nucleotide polymorphisms, respectively. A phylogeny analysis of the re-sequenced accessions substantiated the classification of A. hybridus as the progenitor species of the grain amaranths. Lastly, we generated a physical map for A. hypochondriacus using the BioNano optical mapping platform. The physical map spanned 340 Mb and a hybrid assembly using the BioNano optical genome maps nearly doubled the N50 of the assembly to 697 kb. Moreover, we analyzed synteny between amaranth and Beta vulgaris (sugar beet) and estimated, using Ks analysis, the age of the most recent polyploidization event in amaranth.

Les cultivars de bananiers sont dérivés d'hybridations entre sous-espèces de Musa acuminata (génome A) et pour certains avec l'espèce M. balbisiana (génome B). Ces hybrides présentent une fertilité réduite, des méioses perturbées et de fortes distorsions de ségrégation. Ces caractéristiques attribuées à des réarrangements chromosomiques entre espèces et sous-espèces compliquent les analyses génétiques et les programmes d'amélioration variétale. Au cours de cette thèse, nous avons mis en place et testé de nouvelles approches, basées sur la récente disponibilité d'une séquence de référence du bananier et des technologies de séquençage haut-débit, pour caractériser ces différences de structures chromosomiques et comprendre leur impact sur les ségrégations chromosomiques. Ces approches ont nécessité l'amélioration de la séquence de référence du bananier. Pour cela, des outils ont été développés. Ils sont applicables à d'autres génomes et modulables en fonction des données disponibles. Le nombre de scaffolds a été divisé par 5 et 90% de la séquence est maintenant ancré aux chromosomes. Les scaffolds correspondant au génome mitochondrial ont été identifiés et le génome chloroplastique a été assemblé et annoté. Des données de re-séquençage de l'accession ‘Pahang' et de génotypage dense de sa descendance ont été utilisées pour explorer l'origine des distorsions de ségrégation impliquant les chromosomes 1 et 4. L'ensemble des données (profils de distorsion et de recombinaison, appariements à la méiose, re-séquençage), nous orientent vers l'hypothèse d'une translocation réciproque en orientation inversée, entre régions distales des chromosomes 1 et 4. Le test de nos outils de recherche de variations structurales pour comparer les génomes A et B du bananier, dont les différences de structure sont connues, montre que nos outils détectent directement les signatures de certaines variations structurales mais que pour d'autres il ne détecte que des signatures partielles. Ces dernières peuvent néanmoins être informatives en complément d'autres types d'informations provenant de cartographie génétique et d'analyses cytogénétiques. / Banana cultivars are derived from hybridization between Musa acuminata subspecies (A genome) and, for some of them, with the species M. balbisiana (B genome). These hybrids have reduced fertility, disturbed meiosis and strong segregation distortions. These characteristics attributed to chromosomal rearrangements between species and subspecies complicate genetic analyses and breeding programs. In this thesis, we have developed and tested new approaches based on the recent availability of a banana reference genome sequence and high-throughput sequencing technologies, to characterize these differences in chromosomal structures and understand their impact on chromosomal segregation. These approaches needed improvement of the banana reference genome sequence. New bioinformatics tools were developed for this purpose. They are applicable to other genomes and are flexible according to available data. The scaffolds number was divided by 5 and 90% of the assembly is now anchored to the chromosomes. Scaffolds corresponding to the mitochondrial genome were identified and the chloroplast genome was assembled and annotated. Re-sequencing data from the 'Pahang' accession and dense genotyping of its progeny were used to explore the origin of segregation distortion involving chromosomes 1 and 4. Distortion and recombination profiles, chromosomal pairing at meiosis and re-sequencing data direct us to the hypothesis of a reciprocal translocation in inverted orientation between distal portions of chromosomes 1 and 4. We tested our structural variation research tools to compare the A and B genomes of banana, for which structural differences are known. The results showed that our tools detected complete signatures of some structural changes but for others, they only detected partial signatures. The latter can still be informative in addition to other informations derived from genetic mapping and cytogenetic studies.

Les anomalies du tube neural (ATN) sont des anomalies développementales où le tube neural reste ouvert (1-2/1000 naissances). Afin de prévenir cette maladie, une connaissance accrue des processus moléculaires est nécessaire. L’étiologie des ATN est complexe et implique des facteurs génétiques et environnementaux. La supplémentation en acide folique est reconnue pour diminuer les risques de développer une ATN de 50-70% et cette diminution varie en fonction du début de la supplémentation et de l’origine démographique. Les gènes impliqués dans les ATN sont largement inconnus. Les études génétiques sur les ATN chez l’humain se sont concentrées sur les gènes de la voie métabolique des folates du à leur rôle protecteur dans les ATN et les gènes candidats inférés des souris modèles. Ces derniers ont montré une forte association entre la voie non-canonique Wnt/polarité cellulaire planaire (PCP) et les ATN. Le gène Protein Tyrosine Kinase 7 est un membre de cette voie qui cause l’ATN sévère de la craniorachischisis chez les souris mutantes. Ptk7 interagit génétiquement avec Vangl2 (un autre gène de la voie PCP), où les doubles hétérozygotes montrent une spina bifida. Ces données font de PTK7 comme un excellent candidat pour les ATN chez l’humain. Nous avons re-séquencé la région codante et les jonctions intron-exon de ce gène dans une cohorte de 473 patients atteints de plusieurs types d’ATN. Nous avons identifié 6 mutations rares (fréquence allélique <1%) faux-sens présentes chez 1.1% de notre cohorte, dont 3 sont absentes dans les bases de données publiques. Une variante, p.Gly348Ser, a agi comme un allèle hypermorphique lorsqu'elle est surexprimée dans le modèle de poisson zèbre. Nos résultats impliquent la mutation de PTK7 comme un facteur de risque pour les ATN et supporte l'idée d'un rôle pathogène de la signalisation PCP dans ces malformations. / Neural tube defects (NTDs) are among the most common congenital defects with a high incidence of 1-2 per 1000 births, causing a heavy burden to both the families and society. Various types of NTDs result from defects happening in the neurulation process during vertebrate embryonic development. In order to prevent the occurrence of NTDs, understanding the underlying mechanism is a prerequisite. The etiology of NTDs is complex involving environmental and genetic factors. Folic acid supplementation was proven to efficiently decrease the frequency of NTDs by 50-70% depending on the time point of this supplementation and demographic background. Gene identification studies in NTDs have adopted mainly a candidate gene approach investigating folate-related genes and genes derived from animal models. In particular, studies in mouse models have demonstrated a strong association between the non canonical Wnt/Planar Cell Polarity (PCP) pathway and NTDs. Protein Tyrosine Kinase 7 (PTK7) is a member of the PCP pathway and was shown to cause a very severe form of NTDs called craniorachischisis in a mouse model. Ptk7 genetically interacts with a core PCP member Vangl2 where double heterozygotes suffer from spina bifida. These data make PTK7 a strong candidate for NTDs in humans. We sequenced the coding region and the exon-intron junctions of PTK7 in a cohort of 473 patients affected with various forms of open and closed NTDs. Novel and rare variants (<1%) were genotyped in a cohort of 473 individuals. Their pathogenic effect was predicted in silico and functionally in an overexpression assay in a well established zebrafish model. We identified in our cohort 6 novel rare mutations, 3 of which are absent in all public databases, in 1.1% of our NTD cohort. One variant, p.Gly348Ser, acted as a hypermorph when overexpressed in the zebrafish model. Our findings implicate mutation of PTK7 as a risk factor for NTDs and provide additional evidence for a pathogenic role of PCP signaling in these malformations.

We have investigated genetic variation in microRNA-mediated regulation as a susceptibility factor for anxiety disorders following two different approaches. We first studied two isoforms of the candidate gene NTRK3 by re-sequencing its different 3'UTRs in patients with Panic (PD) and Obsessive Compulsive disorders (OCD) as well as controls. Two rare variants that altered microRNA-mediated regulation were identified in PD. Conversely, association of a common SNP with OCD hoarding subtype was found. Moreover, we have also studied a possible involvement of microRNAs in anxiety disorders. Consequently, we have analysed the genomic organisation and genetic variation of miRNA-containing regions to construct a panel of SNPs for association analysis. Case-control studies revealed several associations. However, it is worth remarking the associations of miR-22 and miR-488 with PD; two microRNAs for which functional assays and transcriptome analysis after microRNA overexpression showed significant repression of a subset of genes involved in physiological pathways linked to PD development. / Hem investigat la variació genètica a la regulació mediada per microRNAs com a factors de susceptibilitat pels trastorns d'ansietat seguint dues aproximacions diferents. Primer vam estudiar dues isoformes del gen candidat NTRK3 mitjançant la reseqüenciació dels seus diferents 3'UTRs a pacients de pànic (TP), a pacients amb trastorn obsessiu compulsiu (TOC) i a controls. Dues variants rares que alteren la regulació mediada per microRNAs foren identificades per TP. D'altra banda, es trobà associació d'un SNP comú amb el subtipus acumulador de TOC. A més, també hem estudiat la possible implicació dels microRNAs als trastorns d'ansietat. Conseqüentment, hem analitzat l'organització genòmica i la variació genètica a regions que contenen microRNAs per construir un panell d'SNPs per fer anàlisis d'associació. Els estudis cas-control van revelar algunes associacions. Tanmateix, val la pena destacar les associacions del miR-22 i el miR-488 amb TP; dos microRNAs pels quals assajos funcionals i anàlisis de transcriptoma després de la seva sobreexpressió han mostrat una repressió significativa d'un grup de gens implicats en vies fisiològiques lligades al desenvolupament del TP.