Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance.

Down syndrome (DS) is characterized by extensive phenotypic variability, with most traits occurring in only a fraction of affected individuals. Substantial gene-expression variation is present among unaffected individuals, and this variation has a strong genetic component. Since DS is caused by genomic-dosage imbalance, we hypothesize that gene-expression variation of human chromosome 21 (HSA21) genes in individuals with DS has an impact on the phenotypic variability among affected individuals. We studied gene-expression variation in 14 lymphoblastoid and 17 fibroblast cell lines from individuals with DS and an equal number of controls. Gene expression was assayed using quantitative real-time polymerase chain reaction on 100 and 106 HSA21 genes and 23 and 26 non-HSA21 genes in lymphoblastoid and fibroblast cell lines, respectively. Surprisingly, only 39% and 62% of HSA21 genes in lymphoblastoid and fibroblast cells, respectively, showed a statistically significant difference between DS and normal samples, although the average up-regulation of HSA21 genes was close to the expected 1.5-fold in both cell types. Gene-expression variation in DS and normal samples was evaluated using the Kolmogorov-Smirnov test. According to the degree of overlap in expression levels, we classified all genes into 3 groups: (A) nonoverlapping, (B) partially overlapping, and (C) extensively overlapping expression distributions between normal and DS samples. We hypothesize that, in each cell type, group A genes are the most dosage sensitive and are most likely involved in the constant DS traits, group B genes might be involved in variable DS traits, and group C genes are not dosage sensitive and are least likely to participate in DS pathological phenotypes. This study provides the first extensive data set on HSA21 gene-expression variation in DS and underscores its role in modulating the outcome of gene-dosage imbalance.

Comparative population genetic structure in a plant-pollinator/seed predator system.

Comparative analyses of spatial genetic structure of populations of plants and the insects they interact with provide an indication of how gene flow, natural selection and genetic drift may jointly influence the distribution of genetic variation and potential for local co-adaptation for interacting species. Here, we analysed the spatial scale of genetic structure within and among nine populations of an interacting species pair, the white campion Silene latifolia and the moth Hadena bicruris, along a latitudinal gradient across Northern/Central Europe. This dioecious, short-lived perennial plant inhabits patchy, often disturbed environments. The moth H. bicruris acts both as its pollinator and specialist seed predator that reproduces by laying eggs in S. latifolia flowers. We used nine microsatellite markers for S. latifolia and eight newly developed markers for H. bicruris. We found high levels of inbreeding in most populations of both plant and pollinator/seed predator. Among populations, significant genetic structure was observed for S. latifolia but not for its pollinator/seed predator, suggesting that despite migration among populations of H. bicruris, pollen is not, or only rarely, carried over between populations, thus maintaining genetic structure among plant populations. There was a weak positive correlation between genetic distances of S. latifolia and H. bicruris. These results indicate that while significant structure of S. latifolia populations creates the potential for differentiation at traits relevant for the interaction with the pollinator/seed predator, substantial gene flow in H. bicruris may counteract this process in at least some populations.

APOBEC3G genetic variants and their influence on the progression to AIDS.

The cytosine deaminase APOBEC3G, in the absence of the human immunodeficiency virus type 1 (HIV-1) accessory gene HIV-1 viral infectivity factor (vif), inhibits viral replication by introducing G-->A hypermutation in the newly synthesized HIV-1 DNA negative strand. We tested the hypothesis that genetic variants of APOBEC3G may modify HIV-1 transmission and disease progression. Single nucleotide polymorphisms were identified in the promoter region (three), introns (two), and exons (two). Genotypes were determined for 3,073 study participants enrolled in six HIV-AIDS prospective cohorts. One codon-changing variant, H186R in exon 4, was polymorphic in African Americans (AA) (f = 37%) and rare in European Americans (f < 3%) or Europeans (f = 5%). For AA, the variant allele 186R was strongly associated with decline in CD4 T cells (CD4 slope on square root scale: -1.86, P = 0.009), The 186R allele was also associated with accelerated progression to AIDS-defining conditions in AA. The in vitro antiviral activity of the 186R enzyme was not inferior to that of the common H186 variant. These studies suggest that there may be a modifying role of variants of APOBEC3G on HIV-1 disease progression that warrants further investigation.

The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome.

Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS without CHD as controls. Chromosome 21-specific association studies revealed rs2832616 and rs1943950 as CHD risk alleles (adjusted genotypic P-values <0.05). These signals were confirmed in a replication cohort of 92 DS-CHD cases and 80 DS-without CHD (nominal P-value 0.0022). Furthermore, CNV analyses using a customized chromosome 21 aCGH of 135K probes in 55 DS-AVSD and 53 DS-without CHD revealed three CNV regions associated with AVSD risk (FDR ≤ 0.05). Two of these regions that are located within the previously identified CHD region on chromosome 21 were further confirmed in a replication study of 49 DS-AVSD and 45 DS- without CHD (FDR ≤ 0.05). One of these CNVs maps near the RIPK4 gene, and the second includes the ZBTB21 (previously ZNF295) gene, highlighting the potential role of these genes in the pathogenesis of CHD in DS. We propose that the genetic architecture of the CHD risk of DS is complex and includes trisomy 21, and SNP and CNV variations in chromosome 21. In addition, a yet-unidentified genetic variation in the rest of the genome may contribute to this complex genetic architecture.

Random regression models to estimate genetic parameters for milk production of Guzerat cows using orthogonal Legendre polynomials

The objective of this work was to compare random regression models for the estimation of genetic parameters for Guzerat milk production, using orthogonal Legendre polynomials. Records (20,524) of test-day milk yield (TDMY) from 2,816 first-lactation Guzerat cows were used. TDMY grouped into 10-monthly classes were analyzed for additive genetic effect and for environmental and residual permanent effects (random effects), whereas the contemporary group, calving age (linear and quadratic effects) and mean lactation curve were analized as fixed effects. Trajectories for the additive genetic and permanent environmental effects were modeled by means of a covariance function employing orthogonal Legendre polynomials ranging from the second to the fifth order. Residual variances were considered in one, four, six, or ten variance classes. The best model had six residual variance classes. The heritability estimates for the TDMY records varied from 0.19 to 0.32. The random regression model that used a second-order Legendre polynomial for the additive genetic effect, and a fifth-order polynomial for the permanent environmental effect is adequate for comparison by the main employed criteria. The model with a second-order Legendre polynomial for the additive genetic effect, and that with a fourth-order for the permanent environmental effect could also be employed in these analyses.

Multiple introductions boosted genetic diversity in the invasive range of black cherry (Prunus serotina; Rosaceae).

BACKGROUND AND AIMS: Black cherry (Prunus serotina) is a North American tree that is rapidly invading European forests. This species was introduced first as an ornamental plant, then it was massively planted by foresters in many countries, but its origins and the process of invasion remain poorly documented. Based on a genetic survey of both native and invasive ranges, the invasion history of black cherry was investigated by identifying putative source populations and then assessing the importance of multiple introductions on the maintenance of gene diversity. METHODS: Genetic variability and structure of 23 populations from the invasive range and 22 populations from the native range were analysed using eight nuclear microsatellite loci and five chloroplast DNA regions. KEY RESULTS: Chloroplast DNA diversity suggests there were multiple introductions from a single geographic region (the north-eastern United States). A low reduction of genetic diversity was observed in the invasive range for both nuclear and plastid genomes. High propagule pressure including both the size and number of introductions shaped the genetic structure in Europe and boosted genetic diversity. Populations from Denmark, The Netherlands, Belgium and Germany showed high genetic diversity and low differentiation among populations, supporting the hypothesis that numerous introduction events, including multiple individuals and exchanges between sites, have taken place during two centuries of plantation. CONCLUSIONS: This study postulates that the invasive black cherry has originated from east of the Appalachian Mountains (mainly the Allegheny plateau) and its invasiveness in north-western Europe is mainly due to multiple introductions containing high numbers of individuals.

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors.

ABSTRACT: BACKGROUND: The Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as somatic and sociodemographic characteristics of the sample. METHODS: All 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was gathered on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree family members, whereas the collection of DNA and plasma samples was part of the original somatic study (CoLaus). RESULTS: A total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam. CONCLUSIONS: Despite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders.

Division of labor in insect societies : genetic components and physiological regulation

The shift from solitary to social organisms constitutes one of the major transitions in evolution. The highest level of sociality is found in social insects (ants, termites and some species of bees and wasps). Division of labor is central to the organization of insect societies and is thought to be at the root of their ecological success. There are two main levels of division of labor in social insect colonies. The first relates to reproduction and involves the coexistence of queen and worker castes: while reproduction is usually monopolized by one or several queens, functionally sterile workers perform all the tasks to maintain the colony, such as nest building, foraging or brood care. The second level of division of labor, relating to such non-reproductive duties, is characterized by the performance of different tasks or roles by different groups of workers. This PhD aims to better understand the mechanisms underlying division of labor in insect societies, by investigating how genes and physiology influence caste determination and worker behavior in ants. In the first axis of this PhD, we studied the nature of genetic effects on division of labor. We used the Argentine ant Linepithema humile to conduct controlled crosses in the laboratory, which revealed the existence of non-additive genetic effects, such as parent-of-origin and genetic compatibility effects, on caste determination and worker behavior. In the second axis, we focused on the physiological regulation of division of labor. Using Pogonomyrmex seed- harvester ants, we performed experimental manipulation of hibernation, hormonal treatments, gene expression analyses and protein quantification to identify the physiological pathways regulating maternal effects on caste determination. Finally, comparing gene expression between nurses and foragers allowed us to reveal the association between vitellogenin and worker behavior in Pogonomyrmex ants. This PhD provides important insights into the role of genes and physiology in the regulation of division of labor in social insect colonies, helping to better understand the organization, evolution and ecological success of insect societies. - L'une des principales transitions évolutives est le passage de la vie solitaire à la vie sociale. La socialité atteint son paroxysme chez les insectes sociaux que sont les fourmis, les termites et certaines espèces d'abeilles et de guêpes. La division du travail est la clé de voûte de l'organisation de ces sociétés d'insectes et la raison principale de leur succès écologique. La division du travail s'effectue à deux niveaux dans les colonies d'insectes sociaux. Le premier niveau concerne la reproduction et implique la coexistence de deux castes : les reines et les ouvrières. Tandis que la reproduction est le plus souvent monopolisée par une ou plusieurs reines, les ouvrières stériles effectuent les tâches nécessaires au bon fonctionnement de la colonie, telles que la construction du nid, la recherche de nourriture ou le soin au couvain. Le second niveau de division du travail, qui concerne les tâches autres que la reproduction, implique la réalisation de différents travaux par différents groupes d'ouvrières. Le but de ce doctorat est de mieux comprendre les mécanismes sous-jacents de la division du travail dans les sociétés d'insectes en étudiant comment les gènes et la physiologie influencent la détermination de la caste et le comportement des ouvrières chez les fourmis. Dans le premier axe de ce doctorat, nous avons étudié la nature des influences génétiques sur la division du travail. Nous avons utilisé la fourmi d'Argentine, Linepithema humile, pour effectuer des croisements contrôlés en laboratoire. Cette méthode nous a permis de révéler l'existence d'influences génétiques non additives, telles que des influences dépendantes de l'origine parentale ou des effets de compatibilité génétique, sur la détermination de la caste et le comportement des ouvrières. Dans le second axe, nous nous sommes intéressés à la régulation physiologique de la division du travail. Nous avons utilisé des fourmis moissonneuses du genre Pogonomyrmex pour effectuer des hibernations artificieHes, des traitements hormonaux, des analyses d'expression de gènes et des mesures de vitellogénine, ce qui nous a permis d'identifier les mécanismes physiologiques régulant les effets maternels sur la détermination de la caste. Enfin, la comparaison d'expression de gènes entre nourrices et fourrageuses suggère un rôle de la vitellogénine dans la régulation du comportement des ouvrières chez les fourmis moissonneuses. En détaillant les influences des gènes et de la physiologie dans la régulation de la division du travail dans les colonies d'insectes sociaux, ce doctorat fournit d'importantes informations permettant de mieux comprendre l'organisation, l'évolution et le succès écologique des sociétés d'insectes.

The interplay of spatial and climatic landscapes in the genetic distribution of a South American parrot

AimOur aim was to understand the interplay of heterogeneous climatic and spatial landscapes in shaping the distribution of nuclear microsatellite variation in burrowing parrots, Cyanoliseus patagonus. Given the marked phenotypic differences between populations of burrowing parrots we hypothesized an important role of geographical as well climatic heterogeneity in the population structure of this species. LocationSouthern South America. MethodsWe applied a landscape genetics approach to investigate the explicit patterns of genetic spatial autocorrelation based on both geography and climate using spatial principal component analysis (sPCA). This necessitated a novel statistical estimation of the species climatic landscape, considering temperature- and precipitation-based variables separately to evaluate their weight in shaping the distribution of genetic variation in our model system. ResultsGeographical and climatic heterogeneity successfully explained molecular variance in burrowing parrots. sPCA divided the species distribution into two main areas, Patagonia and the pre-Andes, which were connected by an area of geographical and climatic transition. Moreover, sPCA revealed cryptic and conservation-relevant genetic structure: the pre-Andean populations and the transition localities were each divided into two groups, each management units for conservation. Main conclusionssPCA, a method originally developed for spatial genetics, allowed us to unravel the genetic structure related to spatial and climatic landscapes and to visualize these patterns in landscape space. These novel climatic inferences underscore the importance of our modified sPCA approach in revealing how climatic variables can drive cryptic patterns of genetic structure, making the approach potentially useful in the study of any species distributed over a climatically heterogeneous landscape.

GENETIC DIVERSITY AND STRUCTURE OF Oenocarpus mapora GERMPLASM CONSERVED AT EASTERN AMAZON

ABSTRACT The aim of this study was to evaluate the genetic diversity and structure in the germoplasm of Oenocarpus mapora conserved at Eastern Amazon. Thus, 88 individuals were genotyped with five microsatellite loci. These individuals belong to 24 accessions that were sampled in eight sample places of three Brazilian Amazon states conserved at the Active Germplasm Bank (AGB) of Embrapa Eastern Amazon. All loci were polymorphic and they generated 85 alleles with an average of 17 alleles per loci. Total genetic diversity (HE) was 0.48. Sample places were considered genetically distinct, with ?p = 0.354. The analysis of molecular variance (AMOVA) identified that the genetic portion among areas was of 36.14% and within 63.86%. The Nei distances varied from 0.091 between Abaetetuba and Santo Antônio do Tauá, both in the state of Pará (PA), to 4.18, between Parintins, AM and Rio Branco, AC. By means of Bayesian analysis, it was identified nine clusters that compose the accessions of the germplasm bank, with different distributions among individuals. The study showed high fixation rates per sample area, which indicates that there may have been significant inbreeding or crossing among parental individuals. It suggests that future samples should be made of different plants in natural populations. Even though, it was verified that there is considerable genetic variation in the germplasm of O. mapora.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

BACKGROUND: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. RESULTS: We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.

The genetic basis of color-related local adaptation in a ring-like colonization around the Mediterranean.

Uncovering the genetic basis of phenotypic variation and the population history under which it established is key to understand the trajectories along which local adaptation evolves. Here, we investigated the genetic basis and evolutionary history of a clinal plumage color polymorphism in European barn owls (Tyto alba). Our results suggest that barn owls colonized the Western Palearctic in a ring-like manner around the Mediterranean and meet in secondary contact in Greece. Rufous coloration appears to be linked to a recently evolved nonsynonymous-derived variant of the melanocortin 1 receptor (MC1R) gene, which according to quantitative genetic analyses evolved under local adaptation during or following the colonization of Central Europe. Admixture patterns and linkage disequilibrium between the neutral genetic background and color found exclusively within the secondary contact zone suggest limited introgression at secondary contact. These results from a system reminiscent of ring species provide a striking example of how local adaptation can evolve from derived genetic variation.

GENETIC ARCHITECTURE, EVOLUTION AND MAINTENANCE OF A COLOR CLINE AT A CONTINENTAL SCALE

On a geological time scale the conditions on earth are very variable and biological patterns (for example the distributions of species) are very dynamic. Understanding large scale patterns of variation observed today thus requires a deep understanding of the historical factors that drove their evolution. In this thesis, we reevaluated the evolution and maintenance of a continental color cline observed in the European barn owl (Tyto alba) using population genetic tools. The colour cline spans from south-est Europe where most individual have pure white underparts to north and east Europe where most individuals have rufous-brown underparts. Our results globally showed that the old scenario, stipulating that the color cline evolved by secondary contact of two color morphs (white and rufous) that evolved in allopatry during the last ice age has to be revised. We collected samples of about 700 barn owls from the Western Palearctic to establish the first population genetic data set for this species. Individuals were genotyped at 22 microsatellites markers, at one mitochondrial gene, and at a candidate color gene. The color of each individuals was assessed and their sex determined by molecular methods. We first showed that the genetic variation in Western Europe is very limited compared to the heritable color variation. We found no evidences of different glacial lineages, and showed that selection must be involved in the maintenance of the color cline (chapter 1). Using computer simulations, we demonstrated that the post-glacial colonization of Europe occurred from the Iberian Peninsula and that the color cline could not have evolved by neutral demographic processes during this colonization (chapter 2). Finally we reevaluated the whole history of the establishment of the Western Palearctic variation of the barn owl (chapter 3): This study showed that all Western European barn owls descend from white barn owls phenotypes from the Middle East that colonized the Iberian Peninsula via North-Africa. Following the end of the last ice age (20'000 years ago), these white barn owls colonized Western Europe and under selection a novel rufous phenotype evolved (during or after the colonization). An important part of the color variation could be explained by a single mutation in the melanocortin-1-receptor (MC1R) gene that appeared during or after the colonization. The colonization of Europe reached until Greece, where the rufous birds encountered white ones (which reached Greece from the Middle East over the Bosporus) in a secondary contact zone. Our analyses show that white and rufous barn owls in Greece interbreed only to a limited extent. This suggests that barn owls are at the verge of becoming two species in Greece and demonstrates that European barn owls represent an incipient ring species around the Mediterranean. The revisited history of the establishment of the European barn owl color cline makes this model system remarkable for several aspects. It is a very clear example of strong local adaptation that can be achieved despite high gene flow (strong color and MC1R differentiation despite almost no neutral genetic differentiation). It also offers a wonderful model system to study the interactions between colonization processes and selection processes which have, for now, been remarkably understudied despite their potentially ubiquitous importance. Finally it represents a very interesting case in the speciation continuum and appeals for further studying the amount of gene flow that occurs between the color morphs in Greece. -- Sur l'échelle des temps géologiques, les conditions sur terre sont très variables et les patrons biologiques (telle que la distribution des espèces) sont très dynamiques. Si l'on veut comprendre des patrons que l'on peut observer à large échelle aujourd'hui, il est nécessaire de d'abord comprendre les facteurs historiques qui ont gouverné leur établissement. Dans cette thèse, nous allons réévaluer, grâce à des outils modernes de génétique des populations, l'évolution et la maintenance d'un cline de couleur continental observé chez l'effraie des clochers européenne (Tyto alba). Globalement, nos résultats montrent que le scenario accepté jusqu'à maintenant, qui stipule que le cline de couleur a évolué à partir du contact secondaire de deux morphes de couleur (blanches et rousses) ayant évolué en allopatrie durant les dernières glaciations, est à revoir. Afin de constituer le premier jeu de données de génétique des populations pour cette espèce, nous avons récolté des échantillons d'environ 700 effraies de l'ouest Paléarctique. Nous avons génotypé tous les individus à 22 loci microsatellites, sur un gène mitochondrial et sur un autre gène participant au déterminisme de la couleur. Nous avons aussi mesuré la couleur de tous les individus et déterminé leur sexe génétiquement. Nous avons tout d'abord pu montrer que la variation génétique neutre est négligeable en comparaison avec la variation héritable de couleur, qu'il n'existe qu'une seule lignée européenne et que de la sélection doit être impliquée dans le maintien du cline de couleur (chapitre 1). Grâce à des simulations informatiques, nous avons démontré que l'ensemble de l'Europe de l'ouest a été recolonisé depuis la Péninsule Ibérique après les dernières glaciations et que le cline de couleur ne peut pas avoir évolué par des processus neutre durant cette colonisation (chapitre 2). Finalement, nous avons réévalué l'ensemble de l'histoire postglaciaire de l'espèce dans l'ouest Paléarctique (chapitre 3): l'ensemble des effraies du Paléarctique descendent d'effraie claire du Moyen-Orient qui ont colonisé la péninsule ibérique en passant par l'Afrique du nord. Après la fin de la dernière glaciation (il y a 20'000 ans), ces effraies claires ont colonisé l'Europe de l'ouest et ont évolués par sélection le phénotype roux (durant ou après la colonisation). Une part importante de la variation de couleur peut être expliquée par une mutation sur le gène MC1R qui est apparue durant ou juste après la colonisation. Cette vague de colonisation s'est poursuivie jusqu'en Grèce où ces effraies rousses ont rencontré dans une zone de contact secondaire des effraies claires (qui sont remontées en Grèce depuis le Moyen-Orient via le Bosphore). Nos analyses montrent que le flux de gènes entre effraies blanches et rousses est limité en Grèce, ce qui suggère qu'elles sont en passe de former deux espèces et ce qui montre que les effraies constituent un exemple naissant de spéciation en anneaux autour de la Méditerranée. L'histoire revisitée des effraies des clochers de l'ouest Paléarctique en fait un système modèle remarquable pour plusieurs aspects. C'est un exemple très claire de forte adaptation locale maintenue malgré un fort flux de gènes (différenciation forte de couleur et sur le gène MC1R malgré presque aucune structure neutre). Il offre également un très bon système pour étudier l'interaction entre colonisation et sélection, un thème ayant été remarquablement peu étudié malgré son importance. Et il offre finalement un cas très intéressant dans le « continuum de spéciation » et il serait très intéressant d'étudier plus en détail l'importance du flux de gènes entre les morphes de couleur en Grèce.

Classification, comorbidity, heredity, and risk factors of female sexual dysfunctions

Female sexual dysfunctions, including desire, arousal, orgasm and pain problems, have been shown to be highly prevalent among women around the world. The etiology of these dysfunctions is unclear but associations with health, age, psychological problems, and relationship factors have been identified. Genetic effects explain individual variation in orgasm function to some extent but until now quantitative behavior genetic analyses have not been applied to other sexual functions. In addition, behavior genetics can be applied to exploring the cause of any observed comorbidity between the dysfunctions. Discovering more about the etiology of the dysfunctions may further improve the classification systems which are currently under intense debate. The aims of the present thesis were to evaluate the psychometric properties of a Finnish-language version of a commonly used questionnaire for measuring female sexual function, the Female Sexual Function Index (FSFI), in order to investigate prevalence, comorbidity, and classification, and to explore the balance of genetic and environmental factors in the etiology as well as the associations of a number of biopsychosocial factors with female sexual functions. Female sexual functions were studied through survey methods in a population based sample of Finnish twins and their female siblings. There were two waves of data collection. The first data collection targeted 5,000 female twins aged 33–43 years and the second 7,680 female twins aged 18–33 and their over 18–year-old female siblings (n = 3,983). There was no overlap between the data collections. The combined overall response rate for both data collections was 53% (n = 8,868), with a better response rate in the second (57%) compared to the first (45%). In order to measure female sexual function, the FSFI was used. It includes 19 items which measure female sexual function during the previous four weeks in six subdomains; desire, subjective arousal, lubrication, orgasm, sexual satisfaction, and pain. In line with earlier research in clinical populations, a six factor solution of the Finnish-language version of the FSFI received supported. The internal consistencies of the scales were good to excellent. Some questions about how to avoid overestimating the prevalence of extreme dysfunctions due to women being allocated the score of zero if they had had no sexual activity during the preceding four weeks were raised. The prevalence of female sexual dysfunctions per se ranged from 11% for lubrication dysfunction to 55% for desire dysfunction. The prevalence rates for sexual dysfunction with concomitant sexual distress, in other words, sexual disorders were notably lower ranging from 7% for lubrication disorder to 23% for desire disorder. The comorbidity between the dysfunctions was substantial most notably between arousal and lubrication dysfunction even if these two dysfunctions showed distinct patterns of associations with the other dysfunctions. Genetic influences on individual variation in the six subdomains of FSFI were modest but significant ranging from 3–11% for additive genetic effects and 5–18% for nonadditive genetic effects. The rest of the variation in sexual functions was explained by nonshared environmental influences. A correlated factor model, including additive and nonadditive genetic effects and nonshared environmental effects had the best fit. All in all, every correlation between the genetic factors was significant except between lubrication and pain. All correlations between the nonshared environment factors were significant showing that there is a substantial overlap in genetic and nonshared environmental influences between the dysfunctions. In general, psychological problems, poor satisfaction with the relationship, sexual distress, and poor partner compatibility were associated with more sexual dysfunctions. Age was confounded with relationship length but had over and above relationship length a negative effect on desire and sexual satisfaction and a positive effect on orgasm and pain functions. Alcohol consumption in general was associated with better desire, arousal, lubrication, and orgasm function. Women pregnant with their first child had fewer pain problems than nulliparous nonpregnant women. Multiparous pregnant women had more orgasm problems compared to multiparous nonpregnant women. Having children was associated with less orgasm and pain problems. The conclusions were that desire, subjective arousal, lubrication, orgasm, sexual satisfaction, and pain are separate entities that have distinct associations with a number of different biopsychosocial factors. However, there is also considerable comorbidity between the dysfunctions which are explained by overlap in additive genetic, nonadditive genetic and nonshared environmental influences. Sexual dysfunctions are highly prevalent and are not always associated with sexual distress and this relationship might be moderated by a good relationship and compatibility with partner. Regarding classification, the results supports separate diagnoses for subjective arousal and genital arousal as well as the inclusion of pain under sexual dysfunctions.

Genetic variability in salt tolerance during germination of Stylosanthes humilis H.B.K. and association between salt tolerance and isozymes

Variation in salt tolerance of six natural populations of Stylosanthes humilis from three ecogeographic regions, Mata (wet tropical climate), Agreste and Sertão (semi-arid tropical climate) of Pernambuco State, Northeast Brazil, was evaluated on germination in 201 mM NaCl. There were significant differences among families of all populations for germination percentage and of five populations (except Tamandaré, from Mata) for germination rate. Populations from semi-arid regions presented high coefficients of genetic variation, those from Agreste being higher than those from Sertão. Populations from Mata showed low coefficients of genetic variation. The coefficients of genotypic determination were high for five populations, except Tamandaré, both for germination percentage ( > or = 0.89) and for germination rate ( > or = 0.79), indicating the possibility of selection for salt tolerance in these populations. An electrophoretic analysis of esterase and peroxidase isozymes was also performed in the six populations, and correlations were estimated between salt tolerance and allelic frequencies. The analysis of salt tolerant and salt sensitive families of populations from Agreste suggested an association of alleles of a peroxidase locus with salt tolerance during germination in the Caruaru population