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abstract: This dissertation research employs biological distance and mortuary analyses in tandem with historical sources to investigate the degree to which conversion, as opposed to migration, contributed to the spread of Islam in southern Iberia. The dynamics of the 8th century conquest of Iberia by Muslim Arab and Berber forces from North Africa, and the subsequent 800-year period of religious, political, and social change, remain contested and poorly understood. Migration of Islamic peoples to the peninsula once was invoked as the primary vehicle of Islamic influence, but religious conversion, whether true or nominal, increasingly is regarded as a key component of those changes. This dissertation proposes that conversion, whether a prelude to or a component of Islamization, altered social group affiliations and interactions among those living in southern Iberia. Such changes in social relations and the resultant patterns of mate exchange will be recognizable by means of altered biological patterns of phenotypic variation. Through the examination of ~900 individuals from both Iberian and North African skeletal collections, this study concludes that conquest resulted in a great increase in phenotypic variability in the peninsula from the 8th-11th centuries. The data further indicate that males contributed this phenotypic variability to the samples in the Early Conquest period. Females, most frequently from Hispano-Roman Christian groups, appear to have ‘intermarried’ with these early conquerors and with the Muwallads, male Islamic converts, and are included in the early Muslim burial programs. From the 11th to the 14th centuries, the data presented here demonstrate a stasis and even a slight decrease in phenotypic variability in southern Iberia, which may be explained by endogamy among religious groups in this region. / Dissertation/Thesis / Doctoral Dissertation Anthropology 2017

The occurrence of phenotypic and genotypic diversity is the key factor in crop improvement including abiotic stress tolerance. The focal objectives of this study were to evaluate and characterize 74 tropical indica rice breeding lines for phenotypic and genotypic diversity, screening for the most devastating abiotic stresses in rice; drought and salinity at the seedling stage at morpho-physiological and molecular levels. To fulfill these objectives, five studies were conducted in pots; first two experiments aimed at assessing phenotypic and yield variability at seedling and maturity stages respectively; based on several (more than 20) root and shoot traits which exploited a wide range of variability among genotypes for measured traits. Germplasm was then screened for drought stress at two moister regimes, 50%, and 100% moisture levels, under mini-hoop structures. Nine percent of the genotypes exhibited a high tolerance to drought stress, and genotypes IR86638 and IR49830 were identified as the most and least drought tolerant respectively. Germplasm was also screened for salinity tolerance in pure sand pot-culture (a simple, efficient and alternate screening method) at three levels; high salt stress (EC 12 dSm-1), moderate salt stress (EC 6 dSm-1), and control imposed one week after emergence. Thirteen genotypes (17.57%) were identified as highly salt tolerant; genotypes FED 473 and IR85427 were highly salt tolerant and salt sensitive, respectively. Root traits were found more crucial and best descriptors in identifying both salinity and drought tolerant genotypes. Genotypes were further used in Genome-wide Association Study (GWAS) to uncover important SNPs, QTLs or genes related to salinity tolerance. A higher number of significant SNPs were discovered for root traits, indicting the importance of root traits in identifying abiotic stress tolerance in rice. The knowledge gained from this investigation could be useful in breeding for better crop establishment, yield improvement, screening for any abiotic stress tolerance.

La caractérisation phénotypique de l’espèce Torulaspora delbrueckii en conditions œnologiques, à partir de l’étude d’un grand nombre de souches, a permis de mettre en évidence une grande variabilité au sein de cette espèce. En effet, les souches de T.delbrueckii présentent des différences au niveau des durées de phase de latence et de fermentation, des capacités biotiques mais aussi des productions d’éthanol (maximum 12% vol.). Cette variabilité se retrouve également pour la production d’acidité volatile, de glycérol et de certains arômes. Ce travail confirme les faibles productions d’acidité volatile et de glycérol de cette espèce et met en évidence une réponse au stress osmotique différente de celle de l’espèce Saccharomyces cerevisiae. Au final, l’espèce T. delbrueckii présente une grande « pureté » de fermentation et produit peu de composés indésirables comme le sulfure d’hydrogène, les phénols volatils, l’acetoïne, l’acétaldéhyde et le diacétyle. La réalisation de co-inoculations T. delbrueckii / S. cerevisiae sur moûts liquoreux, permet une réduction systématique de l’acidité volatile des vins, en comparaison à une fermentation pure de l’espèce S. cerevisiae, quelque soit la souche de T. delbrueckii utilisée. De plus, la souche T. delbrueckii OXT1 1//2 a permis de complexifier la composition aromatique d’un moût sec issu du cépage Sauvignon blanc (esters fermentaires +25%, phényl-2-éthanol +51% et thiols volatils +31%). Enfin, la mise au point d’un fermenteur à double compartiment, avec une séparation physique des levures tout en conservant l’homogénéité du milieu de culture, a permis d’aborder l’étude des interactions entre ces 2 espèces. Des inhibitions de type « cell-cell contact » ont ainsi été mises en évidence. / The phenotypic characterization of Torulaspora delbrueckii species in enological conditions, using a large number of strains, showed up a wide variability within this species. Indeed, the strains of T. delbrueckii present different fermentative capacities for lag phase and fermentation durations, biotic capacities and ethanol production (up to 12 % vol.). This phenotypic variability is also obtained for the production of volatile acidity, glycerol and certain aroma compounds. This work confirms the low productions of volatile acidity and glycerol of this species and reveals an osmotic stress response distinct from that of Saccharomyces cerevisiae. Finally, the T. delbrueckii species presents a high fermentation purity and produces low levels of undesirable compounds like hydrogen sulfide, volatile phenols, acetoin, acetaldehyde and diacetyl. The realization of co-inoculations T. delbrueckii / S. cerevisiae on high sugar must, allows a systematic reduction of the volatile acidity of wines, in comparison to a pure fermentation of S. cerevisiae. Moreover, co-inoculation with the T. delbrueckii strain OXT1 1 // 2 allowed the increase of aromatic complexity of a Sauvignon blanc dry wine (esters + 25%, 2-phenylethanol +51 % and volatile thiols + 31 %). At last, the development of a fermentor with double compartment allowing a physical separation of yeasts and preserving the homogeneity of culture medium, allowed us to approach the study of yeast interactions. Inhibitions of type “cell-cell contact” have been demonstrated.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2015-12-09T12:17:07Z No. of bitstreams: 1 ricardodeaquinoborges.pdf: 840672 bytes, checksum: 6414dba3c9de6388b9e4567420cd158e (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2015-12-09T13:49:35Z (GMT) No. of bitstreams: 1 ricardodeaquinoborges.pdf: 840672 bytes, checksum: 6414dba3c9de6388b9e4567420cd158e (MD5) / Made available in DSpace on 2015-12-09T13:49:35Z (GMT). No. of bitstreams: 1 ricardodeaquinoborges.pdf: 840672 bytes, checksum: 6414dba3c9de6388b9e4567420cd158e (MD5) Previous issue date: 2015-02-27 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / A variabilidade quanto ao padrão de coloração da asa é uma característica de Mahanarva spectabilis (Distant, 1909), importante praga em forrageiras. O objetivo deste trabalho foi avaliar se há diferenças de fertilidade e predominância dos padrões alares obtidos de cruzamento de M. spectabilis, bem como diferenças moleculares entre os padrões alares. Espécimes de M. spectabilis foram separados conforme o padrão alar ((AN) amarelo-palha com manchas negras, (VN) avermelhado com manchas negras, (V) totalmente avermelhada, (N) totalmente negra) e separados para reprodução, tendo a prole avaliada quanto ao padrão alar. A fertilidade, medida em número de ovos, e os padrões obtidos na geração F1 foram submetidos a análise de variância (ANOVA) seguida do teste de média Scott-Knott (P< 0,05). No teste de variabilidade genética, adultos das três espécies tiveram o DNA extraído com brometo de cetiltrimetilamônio (CTAB) e testados com marcadores moleculares. A presença ou ausência de bandas gerou uma tabela binária utilizada nos diversos tipos de análises (diversidade (índice Jaccard), componentes principais (PCA), variância molecular (AMOVA) e média aritmética de grupos de pares não ponderados (UPGMA)). Constatou-se que o número de ovos diminuiu significativamente quando o cruzamento envolveu um macho do padrão AN e que o fenótipo dos parentais foi determinante na fertilidade e no padrão da descendência. Os marcadores moleculares utilizados geraram marcas exclusivas que separou M. spectabilis das espécies utilizadas como padrões externos (Mahanarva fimbriolata, Mahanarva tristis), mas não com relação aos diferentes padrões alares de M. spectabilis. Diferenças entre as indivíduos separados geograficamente foram perceptíveis. / The variability in the pattern of wing coloring is a characteristic of Mahanarva spectabilis (Distant, 1909), an important pest in forages. The objective of this study was to evaluate if there is fertility differences and dominance of alar patterns obtained from crossing M. spectabilis and molecular differences between the wing standards. Specimens M. spectabilis were separated according to the standard wing ((AN) straw yellow to black spots (RCV) to reddish black spots, (V) fully red, (C) totally black) and separated for reproduction having the offspring evaluated for standard wing. The fertility, measured in number of eggs, and the patterns obtained in the F1 generation were subjected to analysis of variance (ANOVA) test followed average Scott- Knott (P <0.05). In the genetic variability test, adults of all three species had DNA extracted with cetyltrimethylammonium bromide (CTAB) and tested with molecular markers. The presence or absence of bands generated binary table used in various types of analyzes (diversity (Jaccard Index), principal components (PCA), molecular variance (AMOVA) and non-weighted arithmetic average of peer groups (UPGMA)). It was found that the number of eggs decreased significantly when the crossing involved a standard male AN and that the phenotype of the parent was instrumental in fertility and the seed pattern. The molecular primers produced exclusive brands that separated M. spectabilis species used as external standards (Mahanarva fimbriolata, Mahanarva tristis), but not with respect to different standards of wings of M. spectabilis. Differences between geographically separated individuals were noticeable.

Herz-Kreislauf-Erkrankungen als Folge arteriosklerotischer Prozesse sind die häufigste Todesursache weltweit. Lipidstoffwechselstörungen sind ein wichtiger Risikofaktor für die Pathogenese der Arteriosklerose. Komplexe Phänotypen, wie z.B. der Lipidstoffwechsel, werden durch eine Vielzahl von genetischen und Umweltfaktoren beeinflusst. Obwohl der Lipidstoffwechsel biochemisch gut charakterisiert ist und viele Gene, die für Proteine innerhalb des Lipidstoffwechsels kodieren bekannt sind, sind die spezifischen genetischen Faktoren, die die Variabilität des Lipidstoffwechsels beeinflussen, weitgehend unbekannt. Die vorgelegten Studien zeigen verschiedene Ansätze, wie genetische Faktoren, die die Variabilität des Lipidstoffwechsels beeinflussen, identifiziert und quantifiziert werden können. Dabei wird ein besonderer Schwerpunkt auf die Untersuchung der Variabilität im nicht-pathologischen Bereich des Stoffwechsels gelegt. Im Rahmen der durchgeführten Arbeiten wurden: 1. modifizierende Genorte bei familiären Hyperlipidämien identifiziert. Dieser Ansatz wurde am Beispiel von zwei Familien mit familiärer Hypercholesterinämie aus Israel und Syrien illustriert. Mit Hilfe der Familie aus Israel wurde ein Genort, der für einen Cholesterin-senkenden Effekt verantwortlich ist, kartiert. Mit Hilfe der Familie aus Syrien wurde ein Gen für die Ausprägung von Xanthomen postuliert. 1. der Einfluß von Genen und Genorten auf die Variabilität des Lipidstoffwechsels in einer Zwillingspopulation nachgewiesen. Dieser Anstz wurde anhand von Genorten auf Chromosom 13q (Cholesterin-senkender Genort), auf Chromosom 8 (Lipioprotein Lipase und Makrophagen Scavenger Rezeptor) und dem PPAR?-Gen auf Chromosom 3 illsutriert. 3. der Einfluß einzelner genetischer Varianten in sechs Kandidatengenen des Lipidstoffwechsels in einer familienbasierten Stichprobe quantifiziert. 4. ein mathematisches Modell des Lipidstoffwechsels entwickelt, mit dem Ziel, sich der Komplexität des Stoffwechsels sowohl von experimenteller als auch von theoretischer Seite her zu nähern. / Cardiovascular disease resultung from atherosclerotic processes are the most commonest cause of death worldwide. Lipid disturbances are a major risk factor in the pathogenesis of atherosclerosis. Complex phenotypes, e.g. lipid metabolism, are influenced by a variety of genetic and environmental factors. Although lipid metabolism is well characterized biochemically and many genes, coding for proteins of lipid metabolism are known, the specific genetic variants, influencing the variability of lipid metabolism are largely unknown. The studies presented show different approaches to the identification of genetic factors contributing quantitatively and qualitatively to the variability of lipid metabolism. This work puts an emphasis on the variability in the non-pathological range of lipid concentrations. The following issues are addressed in the context of this work: 1. Identification of modifying genes of familial lipid disorders. This approach is illustrated for two families with familial hypercholesterolemia from Israel and Syria. The family from Israel allowed the mapping and identification of a cholesterol-lowering gene locus. The family from Syria helped postulating a giant xanthoma gene. 2. The influence of genes and gene loci on the variability of lipid metabolism using a twin cohort. This approach was illustrated for gene loci on chromosome 13q (cholesterol-lowering gene locus), chromosome 8 (Lipoprotein lipase and macrophage scavenger receptor gene locus), and the PPAR?-gene on chromosome 3. 3. The influence of single nucleotide polymorphisms in six lipid metabolism relevant genes using a family based association approach. 5. A mathematical model of lipid metabolism was developed. The goal was to approach the complexity of lipid metabolism experimentally as well as theoretically.

La dystrophie myotonique de type 1 (DM1) est une maladie à transmission autosomale dominante causée par une répétition trinucléotidique CTG située dans la région 3’ non-traduite du gène dystrophia myotonica protein kinase (DMPK). La prévalence mondiale de la DM1 est de 8,26 personnes atteintes par 100 000 habitants : celle-ci est presque 20 fois plus importante au Saguenay-Lac-St-Jean en raison d’un effet fondateur. La présentation clinique de la DM1 peut comprendre divers symptômes dont de la faiblesse musculaire, de la myotonie, des cataractes, de l’insuffisance respiratoire, de l’arythmie cardiaque, de l’hypersomnolence et des troubles cognitifs et endocriniens. Par ailleurs, une grande variation dans la présence et la sévérité de ces symptômes est observée chez les patients et celle-ci n’est qu’en partie expliquée par la longueur des répétitions CTG. Plusieurs mécanismes pourraient expliquer la variabilité inexpliquée dont les défauts d’épissage, la mauvaise régulation des facteurs de transcription, la traduction non-ATG associée aux répétitions et les modifications épigénétiques, en particulier la méthylation de l’ADN. L’objectif de ce projet était donc d’évaluer l’impact de la méthylation de l’ADN au locus DMPK sur la variabilité phénotypique des patients atteints de DM1. Nous rapportons que la méthylation de l’ADN mesurée en amont et en aval de la répétition CTG est respectivement corrélée négativement et positivement avec la longueur de la répétition CTG. La présence d’une interruption de la répétition est associée à un niveau plus élevé de méthylation de l’ADN. À l’aide de modèles de régression linéaire multiple, nous démontrons que la méthylation de l’ADN contribue significativement et indépendamment de la longueur des répétitions CTG, à expliquer la variabilité́ de la force des dorsifléchisseurs de la cheville, de la force de préhension, de la force des pinces, de la capacité́ vitale forcée, du débit expiratoire de pointe, de la pression expiratoire et inspiratoire maximale. La méthylation de l’ADN explique une fraction de la variabilité phénotypique en DM1 et en association avec la longueur de la répétition CTG pourrait aider à améliorer la prédiction de la progression de la maladie chez ces patients. / Abstract : Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by a CTG repeat extension in the 3’ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Worldwide, the prevalence of DM1 is 8.26 affected persons per 100 000 persons, but it goes up to 158 affected persons per 100 000 in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) due to a founder effect. Clinical presentation includes muscular weakness, myotonia, cataracts, respiratory insufficiency, cardiac arrhythmia, hypersomnolence and endocrine and cognitive problems. There is a large variability in the presence and severity of these symptoms that is only partially explained by the CTG repeat length. Many mechanisms such as splicing defects, impaired regulation of transcription factors, repeat-associated non-ATG translation and epigenetic modifications, including DNA methylation, may explain this variability. The objective of this study was to assess the impacts of DNA methylation measured at the DMPK gene locus on phenotypic variability in DM1. We report that DNA methylation upstream of the repeat was negatively correlated with CTG repeat length whereas downstream DNA methylation was positively correlated. The presence of a variant repeat within the CTG repeat was associated with a higher level of DNA methylation. Linear multiple regression models support that DNA methylation contributes significantly and independently of the CTG repeat length to the variability of the ankle dorsiflexor, grip and pinch strengths, as well as forced vital capacity, peak expiratory flow and maximal inspiratory and expiratory pressures. DNA methylation could thus explain part of the phenotypic variability in DM1 and, together with CTG repeat length, could help improve the prediction of the progression of the disease.

La forte variation climatique, notamment de la température qui est associée à la distribution altitudinale de certains peuplements d’arbres forestiers peut induire des pressions de sélection divergentes favorisant l’expression de phénotypes différents en fonction de l’altitude. Cette thèse a pour objectif de déterminer si des adaptations locales existent et peuvent être mises en évidence dans un peuplement de mélèze (Larix decidua Mill.) distribué le long d’un gradient altitudinal situé dans les Alpes françaises, à proximité de Briançon. Quatre placettes d’environ 200 mélèzes ont été délimitées à 2300 m, 2000 m, 1700 m et 1350 m d’altitude le long de ce gradient. Une variabilité phénotypique significative a été observée entre ces niveaux altitudinaux pour la plupart des caractères étudiés : circonférence, hauteur de l’arbre, pourcentage d’aubier ainsi que pour toutes les variables microdensitométriques de cernes sauf une (la largeur de cerne). Une analyse de génétique des populations utilisant des marqueurs microsatellites a mis en évidence une faible influence de la dérive génétique sur la diversité génétique et une forte intensité de flux de gènes entre les différents niveaux altitudinaux étudiés. La différenciation génétique inter-altitudes a été estimée à l’aide d’une approche in-situ basée sur les données phénotypiques seules (PST) et comparée à la différenciation observée à l’aide des marqueurs microsatellites (FST). Cette analyse indique que l’hypothèse d’adaptations locales avec l’altitude peut être raisonnablement avancée pour les caractères de hauteur, circonférence, pourcentage d’aubier et densité du bois initial. Au contraire, l’adaptation locale n’apparait pas comme une hypothèse acceptable pour les caractères de largeur de cerne, surface de cerne, largeur du bois final et densité du bois final. / The strong climatic variation, in particular the temperature variation, which is associated with the altitudinal distribution of certain stands of forest trees, can induce different divergent selection pressure favoring altitude-dependent phenotype expression. The aim of the present thesis is to determine if local adaptation exists and can be identified in an European larch stand (Larix decidua Mill.) distributed along an altitudinal gradient located in the French Alps near Briançon. four plots of about 200 larches were delimited at 2300 m, 2000 m, 1700 m and 1350 m along this altitudinal gradient. A significant phenotypic variability was observed between these altitudinal levels for most characters studied: circumference, tree height, percentage of sapwood and for all the annual-ring microdensity variables except one (ring width). A population genetics analysis using microsatellite markers showed a small effect of genetic drift on the genetic diversity but an intensive gene flow between the altitudinal levels studied. The inter-altitudinal genetic differentiation was estimated using an in-situ approach based on phenotypic data only (PST) and compared with the differentiation observed by means of microsatellite markers (FST). This analysis indicates that the assumption of local adaptation with altitude can be reasonably proposed for the characters of height, circumference, percentage of sapwood and earlywood density. On the contrary, the local adaptation does not appear to be an acceptable assumption concerning characters such as ring width, ring surface area, latewood width and latewood density.

<p>Sagledavanje ukupnog genetičkog i fenotipskog diverziteta i evolucionog potencijala vrste E. tenax izvr&scaron;eno je analizom jedinki poreklom sa 42 područja Evrope, Australije, Severne i Južne Amerike i laboratorijske kolonije iz &Scaron;panije. Analiza intraspecijske varijabilnosti vrste E. tenax izvr&scaron;ena je kvantifikovanjem varijacija u veličini i obliku krila 1653 jedinke i obojenosti abdomena 936 jedinki. Analiza genetičkog diverziteta na nivou polimorfizma nukleotidnih sekvenci mtDNK je izvr&scaron;ena kod 58 jedinki, dok je analiza alozimske varijabilnosti obuhvatila 821 jedinku prirodnih populacija i laboratorijske kolonije vrste E. tenax. Rezultati su ukazali da inbriding i stohastički procesi utiču na redukciju genetičkog diverziteta i da &ldquo;oslobađaju&rdquo; skrivenu genetičku varijabilnost koja je povezana sa fenotipskom diferencijacijom. Vremenska distribucija fenotipskog diverziteta vrste E. tenax je kvantifikovana analizom jedinki četiri alohrona uzorka poreklom sa lokaliteta Venac, Fru&scaron;ka gora. Mali stepen genetičke i fenotipske diferencijacije između durmitorskih uzoraka vrste E. tenax ukazuje na odsustvo prostorne substruktuiranosti i njihovu međusobnu povezanost intenzivnim protokom gena. Analiza konspecifičkih populacija vrsta E. tenax ukazala je na odsustvo jasne međupopulacione diferencijacije na osnovu parametrara krila i molekularnih markera (alozimski lokusi i COI mtDNK), te se može zaključiti da postoji intenzivan protok gena koji elimini&scaron;e razlike između populacija. Registrovan je polni dimorfizam u veličini i obliku krila i obojenosti abdomena. Uočeno je da mužjaci u proseku imaju manja i uža krila i svetlije obojene abdomene od ženki. Analizom fenotipske diferencijacije u karakterima abdomena na uzorcima vrste E. tenax sakupljenim duž geografskog gradijenta Evrope je utvrđeno odsustvo promena po tipu kline. Dobijeni rezultati omogućavaju preciznije sagledavanje intra- i interpopulacione varijabilnosti ovog takona i ukazuju da vrsta E. tenax ima visok evolucioni potencijal za adaptacije na sredinske promene</p> / <p>This paper examines molecular and phenotypic variability in the widely spread hoverfly species Eristalis tenax. We compared 42 samples from Europe, Australia North and South America, with the aim of obtaining insights into the temporal and spatial variations and sexual dimorphism in the species. Additionally, wild specimens from Spain were compared with a laboratory colony reared on artificial media. The integrative approach was based on allozyme loci, cytochrome c oxidase I mitochondrial DNA, morphometric wing parameters (shape and size) and abdominal colour patterns. Our results indicate that the fourth and eighth generations of the laboratory colony show a severe lack of genetic diversity compared to the figures observed in natural populations. Reduced genetic diversity in subsequent generations of the laboratory colony was found to be linked with phenotypic divergence. The distribution of genetic diversity at polymorphic loci indicated genetic divergence among collection dates from Fru&scaron;ka Gora Mt, and landmark-based geometric morphometrics revealed significant wing shape variation throughout the year. Phenotypic differentiation in abdominal pattern of the E. tenax populations along latitudinal gradient Europe has not been established. Consistent sexual dimorphism was observed, indicating that male specimens had lighter abdomens and smaller and narrower wings than females. It is reasonable to assume high mobility of the dronefly and high rate of gene flow reflected the similarity of genetic and phenotypic diversity of otherwise geographically distinct populations. Hence, the present study expands our knowledge of the genetic diversity and phenotypic variability of E. tenax. The quantification of such variability represents a step towards the evaluation of the adaptive potential of this species of medical and epidemiological importance.</p>

Le syndrome CHARGE est une maladie génétique rare dont l’acronyme désigne les principales anomalies initialement identifiées pour décrire ce syndrome : colobome, problèmes cardiaques, atrésie des choanes, retard mental et de développement, anomalies génitales et défauts aux oreilles. Les patients présentent des combinaisons hautement variables d’anomalies et ce même entre individus d’une même famille. La principale cause de ce syndrome est une mutation du gène CHD7, mais de nouveaux gènes dont la mutation peut également engendrer ce syndrome, tel FAM172A , ont récemment été identifiés. Le modèle murin Toupee porte une mutation dans le gène Fam172a et présente les principales caractéristiques du syndrome CHARGE. Fait intéressant, si FVBToupee présente dans une forte proportion le colobome oculaire, 55% des individus B6ToupeeTg/Tg et 16% des individus B6ToupeeTg/+ présentent de la microphtalmie et de l’anophtalmie. Ces anomalies oculaires ont tout d’abord été caractérisées. Les études menées ont notamment permis d’identifier que chez B6Toupee la microphtalmie et l’anophtalmie sont beaucoup plus fréquentes dans l’œil droit et qu’elles se déclinent en plusieurs degrés variables d’atteinte au globe oculaire. Par la suite, l’étude comparative des modèles ToupeeTg/Tg et Chd7Gt/+a été réalisée dans les fonds génétiques FVB et C57Bl/6. Des différences significatives de pénétrance de même que des divergences phénotypiques ont permis de déterminer que l’identité du gène à l’origine du syndrome CHARGE et que le fond génétique modulent tous deux le développement phénotypique du syndrome CHARGE. Finalement, l’étude de doubles hétérozygotes FVBToupeeTg/+ ;Chd7Gt/+ a permis de confirmer une interaction génétique modérée entre Fam172a et Chd7 tandis que l’investigation de la mortalité néonatale chez Chd7Gt/+ a permis de suspecter des problèmes d’alimentation. / CHARGE syndrome is a rare genetic disease for which the acronym stands for the main characteristics initially identified to describe the syndrome: coloboma, heart problems, choanal atresia, retarded growth and development, genital anomalies and ear defects. Patients present highly variable combinations of anomalies, even between members of the same family. The main cause of this syndrome is a mutation in the CHD7 gene, but new genes whose mutation can also give rise to this syndrome, such as FAM172A, were recently identified. The Fam172a gene is mutated in the Toupee mouse model, which presents the main characteristics of CHARGE syndrome. Interestingly, while FVBToupee animals present coloboma in a strong proportion, 55% of B6ToupeeTg/Tg individuals and 16% of B6ToupeeTg/+ individuals present microphthalmia and anophthalmia. First, detailed characterization of these ocular anomalies revealed that microphthalmia and anophthalmia are much more frequent in the right eye of B6Toupee mice, with varying degrees of severity. Then, comparative analysis of ToupeeTg/Tg and Chd7Gt/+models in FVB and C57Bl/6 genetic backgrounds further revealed significant differences in penetrance and phenotypic presentation, suggesting that the identity of the causative gene and the genetic background both modulate phenotypic outcome of CHARGE syndrome. Finally, characterization of FVBToupeeTg/+;Chd7Gt/+ double heterozygotes confirmed a moderate genetic interaction between Fam172a and Chd7 while investigations of Chd7Gt/+ neonatal mortality allowed to suspect feeding problems.