L’interaction de processus génétiques et démographiques peut générer des vortex d’extinction. Chez les Hyménoptères, les mâles sont haploïdes et les femelles diploïdes. Chez les espèces avec sl-CSD (single-locus complementary sex determination), les haploïdes, se développent en mâles et les diploïdes hétérozygotes au gène du CSD, en femelles. Les diploïdes homozygotes sont des mâles non viables ou stériles. Des études théoriques suggèrent que la production de mâles diploïdes peut entraîner les petites populations d’Hyménoptères dans un vortex d’extinction. Le premier objectif est d’encourager le dialogue entre génétique et démographie en proposant une définition des effets Allee élémentaires générés par des processus génétiques, dont nous avons identifié des exemples dans la littérature. Le deuxième objectif est de rechercher l’existence d’un effet Allee génétique dans des populations de Venturia canescens, un Hyménoptère parasitoïde avec sl-CSD. Des marqueurs microsatellites ont été élaborés et utilisés pour montrer une relation négative entre diversité génétique et proportion de mâles diploïdes dans des populations isolées ou goulotées. Les mâles diploïdes s’accouplent mais sont stériles. La dépression de consanguinité affectant les femelles est faible. Nous avons créé et suivi des populations expérimentales de V. canescens avec différents niveaux de diversité génétique. Un effet Allee génétique dû à la production de mâles diploïdes a été détecté mais il n’influençait ni le taux d’accroissement ni la probabilité d’extinction des populations. Les extinctions observées semblent surtout due à la stochasticité démographique. / Genetic and demographic processes can drive small populations to extinction. Their interaction can generate extinction vortices. In Hymenoptera, males are haploid and females are diploid. In species with single-locus complementary sex determination (sl-CSD), hemizygous at the CSD gene develop in males and heterozygous diploids, in females. Homozygous develop in diploids males, often unviable or sterile. Theoretical studies suggest that the production of diploid males associated with demographic and environmental stochasticity may drive small populations into an extinction vortex.The first objective is to stimulate collaboration between genetics and demography by proposing a definition for component Allee effects generated by genetic processes. Component and demographic genetic Allee effects were detected in the literature.The second objective was to investigate the presence of a genetic, and maybe demographic, Allee effect in populations of the parasitoid Venturia canescens, a Hymenoptera with sl-CSD. Microsatellite markers were developed and used to show a negative relationship between genetic diversity and proportion of diploid males in isolated and bottlenecked populations. Diploid males can mate but they are sterile. Inbreeding depression affecting females is negligible. We created and monitored experimental populations of V. canescens with different levels of genetic diversity. A genetic Allee effect due to the production of diploid males was detected but it did not influence the growth rate or the probability of extinction of populations. Extinction events observed thus seem mainly due to demographic stochasticity.

Made available in DSpace on 2014-06-11T19:27:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-08-29Bitstream added on 2014-06-13T19:06:52Z : No. of bitstreams: 1 alonso_rv_me_araca.pdf: 634055 bytes, checksum: 34e27dc3df85046bfbf38cde5c4733bf (MD5) / O crescente avanço da produção in vitro de embriões bovinos intensificou a utilização de outras biotecnologias da reprodução tais como a micro-manipulação embrionária e o diagnóstico genético pré-implantacional, sendo a identificação do sexo embrionário utilizada na rotina comercial de laboratórios de produção in vitro. O objetivo deste trabalho foi avaliar as interações de diferentes fatores sobre a taxa de mortalidade embrionária e a proporção do sexo de embriões bovinos submetidos ao processo de sexagem. Foi realizado levantamento no banco de dados da Transfix – Transplante de Embriões Ltda, Patrocínio Paulista / Brasil, referente a 4.650 embriões produzidos in vitro e sexados entre 2005 e 2007. Os embriões foram submetidos à micro-manipulação pela técnica de micro-aspiração, e as biópsias à reação em cadeia pela polimerase (PCR). Somente as fêmeas foram transferidas para receptoras previamente sincronizadas. O diagnóstico de gestação e a determinação do sexo fetal foram realizados por ultra-sonografia. As variáveis foram classificadas de acordo com o sexo dos embriões (macho, fêmea e indeterminado), cinco laboratórios (A, B, C, D e E), seis raças bovinas (Nelore, Brahman, Girolando, Simental, Holandês e Jersey), estágio embrionário (MO, BI, BL, BX e BE), qualidade embrionária (1, 2 e 3) e qualidade da biópsia (“dentro do padrão” e “fora do padrão”). As análises estatísticas foram realizadas pelos testes 2 de associação, 2 de aderência para proporção 1:1 e pela análise de regressão logística com o método de Hosmer-Lameshow utilizando o procedimento logístico (PROC LOGISTIC) programa computacional SAS. A PCR apresentou eficiência de 93,3%, acurácia de 93,2% e taxa de machos e fêmeas de 52,9% e 47,1%, respectivamente. A taxa de mortalidade dos embriões... / Crescent progress of in vitro bovine embryo production has improved the use of other reproductive biotechnologies, as embryo micromanipulation and preimplantation genetic diagnosis, being embryo sexing used in commercial routine of in vitro embryo production laboratories. The present study aimed to evaluate the interactions among different factors on the mortality rate and sex ratio of in vitro produced bovine embryos. A survey was performed in the Transfix – Transplante de Embriões Ltda, Patrocínio Paulista / Brazil data base, referring to 4.650 in vitro produced bovine embryos sexed during years 2005/2007. Embryos were submited to the biopsy by the microaspiration technique, and biopsies to the polymerase chain reaction (PCR). Only female embryos were transferred to synchronized recipients. Pregnancy diagnosis and fetal sex determination were carried out by ultrasound. The variables were classified according embryo sex (male, female and indeterminate), five laboratories (A, B, C, D and E), six bovine breeds (Nellore, Brahman, Girolando, Simmental, Holstein and Jersey), embryo stage (MO, EB, BL, XB and HB), embryo quality (1, 2, and 3) and biopsy quality (“standard” and “non standard”). The statistical analysis was carried out by association 2 test, 2 for 1:1 ratio and logistic regression analysis with Hosmer- Lameshow method using logistic procedure (PROC LOGISTIC) of SAS package. The PCR showed 93.3% efficiency, 93.2% accuracy and male and female ratio of 52.9% and 47.1%, respectively. Mortality rate of biopsied embryos was 10.3% and pregnancy rate was 31.7%. Although no significant differences were observed between male and female ratio, indeterminate embryos possess greater possibility to die after micromanipulation. For quality 2 and 3 embryo mortality rate after biopsy was 3.19 and 11.37 fold higher, respectively, than for quality 1 embryo. For those whose biopsy... (Complete abstract click electronic access below)

Antropologia Forense é a aplicação da ciência da Antropologia Física e osteologia humana em casos criminais onde os restos da vítima estão em fase avançada de decomposição. Devido ao grande fluxo migratório descrito no histórico do Brasil, a população brasileira possui características físicas muito heterogêneas quando comparadas com a população escocesa, uma vez que a imigração mais significativa foi proveniente de outras regiões do próprio Reino Unido. O presente estudo teve como objetivo comparar as variações craniométricas de duas populações (brasileira e escocesa), e avaliar a confiabilidade do método para determinação do sexo nas duas populações, com finalidade forense. A amostra total foi composta por 200 crânios com mandíbulas, sendo que a amostra brasileira foi constituída por 100 crânios completos e a amostra escocesa por 100 crânios e 36 mandíbulas, ambas amostras documentadas. Foram realizadas 72 mensurações sendo 51 cranianas e 21 mandibulares. Os resultados demonstraram que a amostra escocesa apresentou média maior comparada com a amostra brasileira em 54 variáveis do universo de 72 medidas. Trinta e três mensurações cranianas apresentaram diferença significativa entre as duas amostras e dentre as 21 medidas mandibulares analisadas, 05 apresentaram variação superior a 20%, 09 entre 10% e 20%, 07 inferior a 10%. As medidas que apresentaram maior dimorfismo sexual para as duas amostras foram a largura bizigomática (apresentando 73% de acerto para a amostra brasileira e 77% para a amostra escocesa), largura bigoníaca (79% e 83,30%) comprimento Porion-Mastoidale lado esquerdo (76% e 75%) e a altura do corpo mandibular lado esquerdo (67% e 80,60%). A análise discriminante multivariada demonstrou resultados satisfatórios para amostra brasileira com porcentagem de acerto variando entre 76-90% e na amostra escocesa 81-86,6%. Através da análise da curva ROC foram desenvolvidas 04 tabelas de referência sendo 01 para medidas cranianas brasileiras, 01 medida para mandibulares brasileiras, 01 tabela para medidas cranianas escocesas e 01 para medidas mandibulares escocesas. O presente estudo demonstrou que existem diferenças entre as duas amostras estudadas, porém ainda falta elucidar a causa responsável, já que se trata de uma grandeza multifatorial. A metodologia quantitativa analisada demonstrou-se precisa para analisar dimorfismo sexual nas duas amostras. / Forensic anthropology is the application of the physical anthropology science and human osteology in criminal cases where the victim\'s remains are in an advanced stage of decomposition. Due to migration Brazilian population is very diverse, comprising many races and ethnic groups, therefore it is much more varied than the Scottish population, which tends to be more homogenous once there was significant immigration to Scotland from the rest of the United Kingdom. The present study aimed to compare the craniometric variations of two populations (Brazilian and Scottish), and analyze the reliability of sex determination in the two populations for forensic purpose. The total sample was comprised of 200 skulls and 136 mandibles, the Brazilian sample consisted of 100 complete skulls and the Scottish sample was composed of 100 skulls and 36 mandibles, both of which are documented samples. The measure\'s protocol comprised 72 measurements, being 51 cranial and 21 mandibular. The results showed that the Scottish sample had a larger mean compared to the Brazilian sample in 54 variables of the 72 measures. Among the cranial measurements analyzed, 33 variables showed a significant difference between the two samples and among the 21 mandibular measurements considered, 05 presented a variation greater than 20%, 09 between 10% and 20%, 07 lower than 10%. The most dimorphic measurements for both samples were the bizigomatic width (73% of accuracy for the Brazilian sample and 77% for the Scottish sample), the bigoniac width (79% and 83,30%), the Porion-Mastoidale length (76% and 75%), and the left side mandibular body height (67 and 80,60%). The multivariate discriminant analysis showed satisfactory results for the Brazilian sample with a percentage of accuracy varying between 76-90% and in the Scottish sample 81-86.6%. Through the analysis of the ROC curve, four reference tables were developed: 01 for Brazilian cranial measurements, 01 Brazilian mandibular measurements, 01 Scottish cranial measurements and 01 Scottish mandibular measurements The present study showed a difference between the two samples studied, but it is not possible to define an unique cause responsible for that because this comprise multifactorial aspects. The quantitative methodology analyzed showed sexual dimorphism in both samples.

<p>Down syndrome (DS) is a genetic disorder that results from triplication of human chromosome 21 (Hsa21) and occurs in around 1 in 1000 live births. All individuals with DS present with skeletal abnormalities typified by craniofacial features, short stature and low bone mineral density (BMD). Differences between males and females with DS suggest a sexual dimorphism in how trisomy affects skeletal deficits associated with trisomy 21 (Ts21). Previous investigations of skeletal abnormalities in DS have varied methodology, sample sizes and ages making the underlying causes of deficits uncertain. Mouse models of DS were used to characterize skeletal abnormalities, but the genetic and developmental origin remain unidentified. Over-expression <i>Dyrk1a</i>, found on Hsa21 and mouse chromosome 16 (Mmu16) has been linked to cognitive deficits and skeletal deficiencies. Dp1Tyb mice contain three copies of all of the genes on Mmu16 that are homologous to Hsa21, males and females are fertile, and therefore are an excellent model to test the hypothesis that gene dosage influences the sexual dimorphism of bone abnormalities in DS. Dp1Tyb at 6 weeks 16 weeks showed distinctive abnormalities in BMD, trabecular architecture, and reduced bone strength over time that occur generally through an interaction between sex and genotype. Increased gene dosage and sexual dimorphism in Dp1Tyb mice revealed distinct phenotypes in bone formation and resorption. To assess how <i>Dyrk1a</i> influences the activity and function of osteoblasts Ts65Dn female trisomic mice, female mice with a floxed <i>Dyrk1a</i> gene (Ts65Dn, <i>Dyrk1a</i>^fl/+) were be bred to <i>Osx1</i>-GFP::Cre+ mice to generate Ts65Dn animals with a reduced copy of <i>Dyrk1a </i>in mature osteoblast cells. Female Ts65Dn,<i>Dyrk1a^+/+/+</i>and Ts65Dn,<i>Dyrk1a^+/+/-</i>displayed significant defects in both trabecular architecture and cortical geometry. Ultimate force was reduced in trisomic animals, suggesting whole bone and tissue level properties are not adversely affected by trisomy. Reduction of <i>Dyrk1a</i> functional copy number in female mice did not improve skeletal deficits in an otherwise trisomic animal. <i>Dyrk1a </i>may not alter osteoblast cellular activity in an autonomous manner in trisomic female mice. These data establish sex, gene dosage, skeletal site and age as important factors in skeletal development of the skeleton in DS mice, potentially paving the way for identification of the causal dosage-sensitive genes in both male and female animals. </p>

Determination sex is one of the most important tasks in the identification of skeletal remains. Previous studies have shown that population differences in size and shape of femora can affect correct sex allocation. This thesis tested the discriminat functions generated from different populations and confirmed population specificity of the femur discriminant functions. Two samples of the identified adult femora for this project was used. First sample originates from the Czech population living in the 1st 20th century (78 males and 81 females) and second sample originates from the Czech population living in the 2nd 20th century (67 males and 35 females). Both samples also help us estimate the influence of secular trend of the femur'variables to the correct sex classification by discriminat functions calculated in the Czech population. The results showed the existence of the secular trend in femora size dimensions. Only the dimensions of the femoral head (vertical head diameter-F18, transverse head diameter-F19 and maximum diameter of the femoral head-MPH) and sagittal subtrochanteric diameter (F10) not chandged significantly during the 20th century. The secular trend has negatively influenced the correct sex classification, always for one subpopulation. Only the dimensions in which the secular trend...

Differences in height among human populations or changes in height over time may be associated with different degrees of sexual dimorphism in this feature. This thesis compared the height and sexual size dimorphism (SSD) between two groups of the population of Medieval Bohemia - rural residents and inhabitants of Prague. A sample of 179 adult skeletons from five Prague sites and 175 individuals from four rural sites, dating from the 11th to 14th century, was used. Sex was determined following the principle of primary and secondary sex diagnosis, which enabled the derivation of population-specific discriminant functions using the dimensions of the humerus, femur, tibia and talus. A subsequent analysis of body height did not show statistically significant differences either in height or in SSD between the Prague and the rural part of the population of Medieval Bohemia, despite the major changes which Czech Medieval society went through in the 13th century. Comparing our results with previously published data on the height of the Czech population during the early modern period indicates a statistically significant reduction in the magnitude of sexual size dimorphism in the population of the17th century, particularly associated with a decrease in the height of men. A significantly higher stature of...

Archaeologists have employed a method to determine individuals’ sex through objects in grave contexts, this method is called archaeological sex determination. However, this method has proven to be misleading in interpretations in correlation with the concepts of gender and sex. This will be highlighted through a comparative study of two case studies: “Birkakrigaren” and “Barumskvinnan”. The concept of gender has grown stronger in the public debate concerning the difference between gender and sex, which has contributed to the concept’s amplification in the archaeological discipline, specifically gender theory. Gender theory will be used to explain and clarify the problems of archaeological sex determination, in addition how it could be used for criticism of a current case study, which is “Birkakrigaren” and why the criticism differed between two case studies: “Birkakrigaren” and “Barumskvinnan”. In order to reach the desired results, different articles and books will be examined, simultaneously with articles and blogs on the subject of the criticism.

Recent advances in the methods of skeletal age estimation have rekindled interest in their applicability to paleodemography. The current study contributes to the discussion by applying several long established as well as recently developed or refined aging methods to a subsample of 121 adult skeletons from the early medieval cemetery of Lauchheim. The skeletal remains were analyzed by 13 independent observers using a variety of aging techniques (complex method and other multimethod approaches, Transition Analysis, cranial suture closure, auricular surface method, osteon density method, tooth root translucency measurement, and tooth cementum annulation counting). The age ranges and mean age estimations were compared and results indicate that all methods showed smaller age ranges for the younger individuals, but broader age ranges for the older age groups.

Les gènes des doigts WIP-zinc provenaient de l'établissement de l'évolution rapide du clade Viridiplantae de bryophytes et ptéridophytes. Depuis les bryophytes ancestrales des premières plantes terrestres deux clades principaux ont evolveld, basé sur notre analyse cladistique de la partie C-terminale des WIP. Le thème commun et le caractère démontré par les protéines à doigts de zinc AtWIP sont mis en évidence par leurs découvertes dans des rôles régulateurs de croissance et de développement orgue. Cependant, la protéine moléculaire interagissant partenaires et les mécanismes par lesquels les fonctions de WIP sont orchestrés restent encore inconnues. Ici, nous montrons les interactions entre protéines moléculaires et des modes de localisation sub-cellulaire de CmWIP1 et ses interacteurs pour élucider son rôle de régulateur dans le sexe détermination Cucumis melo fleurs. Sur la base des interactions levures deux écran hybride de protéine-protéine de la banque d'ADNc de melon généré, nous déclarons que la protéine interagit physiquement CmWIP1 très fortement avec CmbZIP et CmLHP1. Aussi interaction n'a été observée avec le complexe CKII en C. melo qui se compose de CmCKIIα, CmCKIIβ1 et CmCKIIβ2 sous-unités. Approches de génétique inverse ont été utilisées pour tenter de valider fonctionnellement les interacteurs clés in planta. Le passage d'homme à fleurs femelles en traits gynoïques résultats de répression épigénétique de l'expression d'un facteur de doigt de zinc de type de transcription, CmWIP1 situé au niveau des loci g dans Cucumis melo. Lorsqu'elle est exprimée, CmWIP1 est responsable de l'avortement carpien entraînant simples fleurs mâles sexués d'une origine bisexuel initial. La surexpression de CmWIP1 (sous promoteur 35SCaMV) chez Arabidopsis thaliana a donné lieu à des plantes présentant un retard de croissance global du-et-dessus des parties sous-sol plantes, feuilles dentelées vrais, des anomalies de croissance floraux et sillique ainsi que médiocre rendement des semences. 35S: CmWIP1 lignées d'insertion développés ont été surveillés en permanence et phénotypées sur T1 à T4 générations pour la stabilité de la dentelure phénotype feuilles. Fait intéressant, deux autres lignes sur-expression portant AtWIP1 et AtWIP2 causés dentelures des feuilles semblables à celles de CmWIP1 surexpression tout sous promoteurs 35SCaMV. Deux lignées stables homozygote pour 35S: CmWIP1 insertion ont été sélectionnés à la génération T4 et muté à 0,3% EMS. Un millier de vracs lignées familiales m2 (5 plants par vrac) ont été examinés pour les personnes réversion avec des feuilles non dentelée et taux de croissance restaurés. Écrans stade végétatif révélé deux révertants putatifs et 7% albinos. Les écrans suivants pour révertants ont été réalisées à des stades de reproduction et également pour les essais de la longueur des racines primaires ont été réalisées afin de valider révertants putatifs. Révertants putatifs familles ont encore été validés en tant que candidats pour la cartographie suppresseur par séquençage Sanger de la 35S :: CmWIP1 insertion par le dépistage de la séquence des mutations qui pourraient être la mutation causale. / The WIP-zinc finger genes originated from the early evolutionary establishment of the Viridiplantae clade from bryophytes and pteridophytes. From the ancestral bryophytes the first terrestrial plants two main clades have evolveld, based on our cladistic analysis of the C-terminal part of the WIPs. From the in silico analysis, CmWIP1 encodes are largely bi-partite protein in nature with the N-terminal acquired for protein-protein interactions whilst the C-terminal part is possibly mainly for DNA binding and some unknown processes involved in chromatin modulation/regulation (the presence of POST-SET domains). The common theme and character demonstrated by the AtWIP-Zinc finger proteins are highlighted by their discoveries in regulatory roles of organ growth and development. However, the molecular protein interacting partners and mechanisms by which the WIP functions are orchestrated still remain unknown. Here we show molecular protein interactions and sub-cellular localization patterns of CmWIP1 and its interactors to elucidate its regulatory role in the sex determination Cucumis melo flowers. Based on the protein-protein interactions yeast two hybrid screen of the melon cDNA library generated, we report that CmWIP1 protein physically interacts very strongly with CmbZIP and CmLHP1. Also interactions were observed with the CKII complex in C. melo which is made up of CmCKIIα, CmCKIIβ1 and CmCKIIβ2 subunits. CmWIP1 also interacts with CmTHF1 and CmPTR. Reverse genetic approaches were utilized in attempts to functionally validate the key interactors in planta. The transition from male to female flowers in gynoecious lines results from epigenetic repression of the expression of a zinc finger type transcription factor, CmWIP1 located at the g loci in Cucumis melo. When expressed, CmWIP1 is responsible for carpel abortion resulting in single sexed male flowers from an initial bisexual origin. Over-expression of CmWIP1 (under 35SCaMV promoter) in Arabidopsis thaliana resulted in plants with overall growth retardation of above- and under-ground plant parts, serrated true leaves, floral and sillique growth abnormalities as well as poor seed yield. 35S:CmWIP1 insertion lines developed were continuously monitored and phenotyped over T1 to T4 generations for stability of the leaf serration phenotype. Interestingly, two other over-expression lines carrying AtWIP1 and AtWIP2 caused leaf serrations similar to that of CmWIP1 overexpression all under 35SCaMV promoters. Two stable lines homozygote for 35S:CmWIP1 insertion were selected at the T4 generation and mutagenized with 0.3 % EMS. A thousand bulks of M2 family lines (5 plants per bulk) were screened for revertant individuals with unserrated leaves and restored growth rates. Vegetative stage screens revealed both putative revertants and 7 % albinos. Subsequent screens for revertants were carried out at the reproductive stages and also for primary root length assays were carried out to validate putative revertants. Putative revertants families were further validated as candidates for suppressor mapping via Sanger sequencing of the 35S::CmWIP1 insert by screening of the sequence for mutations which could be the causative mutation.

Diversos genes expressos durante a diferenciação das células germinativas atuam no desenvolvimento ovariano. A diferenciação das células somáticas ovarianas depende do número de células germinativas pré-meióticas que migram para a fenda gonadal. A expressão espaço-temporal de genes envolvidos na diferenciação dessas células e a posterior sobrevivência dos oócitos meióticos são de interesse no estudo dos distúrbios do desenvolvimento sexual (DDS) 46,XX. Entre os genes envolvidos nesses processos estão o NANOS3, BMP15 e STRA8. O NANOS3, uma molécula de ligação ao RNA que bloqueia a via apoptótica, assegura a sobrevivência das células germinativas durante sua migração para o interior da gônada. O STRA8 atua no início da meiose das células germinativas na gônada de embriões XX, sendo o primeiro sinal de dimorfismo gonadal. Por outro lado a subseqüente sobrevivência dos oócitos é controlada por fatores de transformação e crescimento como o BMP15, que promove a diferenciação das células da granulosa que por sua vez participam indiretamente da diferenciação dos oócitos e das células da teca. Neste trabalho pesquisamos a presença de mutações inativadoras nos genes NANOS3 e BMP15 em 45 pacientes com disgenesia gonadal (DG) 46,XX (10 casos familiais) e 40 pacientes com amenorréia secundária sem mutação nos genes FSHR e SF1. Também pesquisamos mutações nas regiões promotora proximal e codificadora do gene STRA8 de 45 pacientes com DG 46,XX, 16 pacientes com DDS ovotesticular 46,XX e 5 pacientes com DDS testicular 46,XX todos SRY negativo nos quais foram afastados defeitos moleculares nos genes DAX1, WNT4 e SOX9. No NANOS3 identificamos a mutação p.E120K em homozigose, a primeira associada ao fenótipo de DG 46,XX. Esta mutação missense foi identificada em duas irmãs com DG 46, XX e está localizada no domínio de ligação do tipo dedo de zinco da proteína. A nova mutação não foi identificada em 200 alelos controles pesquisados. No BMP15, uma nova mutação nonsense p.Q115X foi identificada em homozigose em duas irmãs com DG 46XX e em heterozigose em uma paciente com amenorréia secundária não familial. O códon de parada prematuro está localizado na região do pré-peptídeo da proteína. A nova mutação não foi identificada em 200 alelos controles pesquisados. No gene STRA8, um único polimorfismo previamente descrito na literatura (rs7805859) foi identificado na região codificadora e nenhuma alteração na região promotora proximal foi identificada. Em conclusão, identificamos pela primeira vez uma mutação no gene NANOS3 associado á DG 46,XX e confirmamos a participação do BMP15 neste fenótipo. Distúrbios do desenvolvimento gonadal 46, XX podem ser causados por mutações em genes envolvidos tanto na diferenciação quanto manutenção das células germinativas ovarianas. / Several genes expressing during the germ cell differentiation act in ovary development. The differentiation of somatic ovary cells depends of a pool of pre meiotic germ cells migration into the gonad. The space and temporal expression pattern of some genes involved with germ cell differentiation and the subsequently oocyte survival should be investigated in the disorders of sexual development (DSD) 46,XX. Some key genes involved with these processes are: NANOS3, BMP15 and STRA8. The NANOS3, a RNA binding molecule that blocks the apoptotic pathway, ensures the survival during migration into genital ridge. The STRA8 acts in the bigining of germ cells meioses in XX embryos and mark the first sexual gonadal dimorphism. In other hand the subsequently oocyte survival is controlled through transforming growth factor member BMP15, that guarantees granulose cells differentiation that acts indirectly in meiotic oocyte and theca cells differentiation. In this work we searched for the presence of inactivating mutations in NANOS3 and BMP15 in 45 patients with 46XX gonadal dysgenesis (10 familial cases) and 40 patients with secondary amenorrhea without FSHR and SF1 mutation. We also searched for inactivating mutations in coding and proximal promoter region of STRA8 in 45 patients with 46XX gonadal dysgenesis, 16 ovotesticular disorder of sex development (DSD) patients and five 46XX testicular DSD patients all SRY negative and molecular defects in DAX1, WNT4 and SOX9 gene. In NANOS3 we identified the mutation p.E120K in homozygous state, the first associated with DG 46,XX phenotype. This missense mutation was identified in two sisters with 46XX GD and affects a zinc finger domain of the protein. The new variant was absent in 200 control alleles. In BMP15, a new nonsense mutation p.Q115X was identified two sisters in homozygous state and in one sporadic case of secondary amenorrhea in heterozygous state. The premature codon STOP affects the pro-peptide domain of the protein. The new variant was absent in 200 control alleles. In STRA8, only a previously described polymorphism (rs7805859) was identified without any other variation in coding or proximal promoter region. In conclusion, we identified for the fist time mutation in NANOS3 associated with DG 46XX and corroborate the role of BMP15 in this phenotype. Disorders of gonadal development 46,XX may be involved with differentiation and maintenance of ovarian germ cells.