In the present study / ten autosomal human-specific Alu insertion polymorphisms / ACE, APO, A25, B65, D1, FXIIIB, HS4.32, HS4.69, PV92 and TPA25 were analyzed in approximately 100 unrelated individuals from Anatolia. Alu insertion polymorphisms offer several advantages over other nuclear DNA polymorphisms for human evolution studies. The frequencies of the ten biallelic Alu insertions in Anatolians were calculated and all systems were found to be in Hardy-Weinberg equilibrium (p&gt / 0.05). By combining the results of this study with results of previous studies done on worldwide populations, the genetic distance (Nei&rsquo / s DA) between each pair of populations was calculated and neighbor joining trees were constructed. In general, geographically closer populations were found to be also genetically similar. Principal component analysis (PCA) was performed and Anatolia was found to be in the European cluster. As a result of PCA / it was concluded that FXIIIB, PV92 and ACE were the variables contributing the most to the explanation of the variation between the populations. Additionally / canonical variates analysis (CVA) concluded that the most discriminative markers for the groups of populations were PV92, D1, ACE and HS4.32. Pair-wise Fst values were also calculated between Anatolians and some of the populations for which the data was available. It was concluded that, Anatolians have non-significant pair-wise Fst values with Swiss and French Acadian populations. Lastly, heterozygosity vs. distance from centroid graph was constructed and it was found that Anatolians and India-Hindu had exactly the expected heterozygosity value predicted by the model of Harpending and Ward (1982).

Many bumblebee species are suffering from the effects of habitat fragmentation and population isolation. In some cases, populations have lost genetic diversity due to genetic drift and it is possible they are now at heightened risk of extinction. Inbreeding may be particularly costly to bumblebees because, as Hymenoptera, their complementary sex determination system can lead to the production of sterile or inviable diploid males. However, little is known about the effect that diploid male production has on bumblebee colony fitness. Here, the consequences of brother-sister mating in the bumblebee Bombus terrestris are investigated, and the production of diploid males was found to exert considerable costs at the colony level by reducing productivity and survival. Diploid males may therefore act as indicators of the genetic health of populations, and their detection could be used as an informative tool in hymenopteran conservation. Due to the costs associated with inbreeding, selection may have favoured the evolution of kin recognition systems in bumblebees. Data are presented that suggest that B. terrestris can discriminate between kin and non-kin as gynes were less willing to mate with siblings compared to non-relatives. Theory predicts that inbreeding may impose further costs on bumblebees through increased levels of parasitism, but empirical data are scarce. The relationship between population genetic diversity and parasite prevalence is assessed using Hebridean island populations of Bombus muscorum and Bombus jonellus. In the more outbred B. jonellus, there was no relationship between parasite prevalence and population heterozygosity. But prevalence of the gut parasite Crithidia bombi and the tracheal mite Locustacarus buchneri were found to be higher in populations of B. muscorum that had lower genetic diversity. In addition to assessing infection status, the activity of the immune system was assessed in each individual bee. However, there was no relationship between population heterozygosity and these immune parameters. This suggests that, in some Hymenopteran species, as populations lose genetic diversity the impact of parasitism will increase, potentially pushing threatened populations closer to extinction. Therefore, preventing population fragmentation by the creation of suitable habitats and by ensuring connectivity between habitat patches are important aspects of hymenopteran conservation. Finally, this thesis investigates the potential threat of pathogen spread from commercially reared bumblebees used for crop pollination to wild bumblebees. Although no direct evidence for parasite spillover is found, the prevalence of C. bombi was significantly higher in B. terrestris by the end of the season on farms that used commercial bumblebees compared to farms that did not. This high prevalence does suggest that pathogen spillover is a potential threat and it would be preferable to reduce the usage of commercial bumblebees where possible. For example, sowing wild flower mixes could boost natural pollinator populations, which in turn would benefit soft fruit pollination. Overall, this thesis contributes to our knowledge of the consequences of inbreeding in bumblebees and the relationship between genetic diversity and parasite prevalence. It provides a greater understanding of the factors that might be pushing threatened pollinators towards extinction and as a whole provides important information that may inform conservation practitioners, whose aim is to protect the future of our hymenopteran pollinators.

La diversité génétique est un paramètre capital pour les populations comme pour les individus. Ainsi, l'hétérozygotie confère généralement un avantage de valeur sélective aux individus dans de nombreux taxa, et il existe divers processus de sélection sexuelle permettant d'optimiser l'hétérozygotie de la descendance. Nous avons testé ces hypothèses chez l'isopode terrestre Armadillidium vulgare. Nous avons pu mettre en évidence un meilleur succès reproducteur des mâles les plus hétérozygotes, qui peut résulter de la compétition intrasexuelle comme du choix de partenaire, ainsi que d'un choix pour un partenaire génétiquement dissimilaire. Ces deux processus ont pour conséquence d'augmenter l'hétérozygotie des descendants. Nous avons aussi décrit pour la première fois un fort taux de paternité multiple dans les populations naturelles comme expérimentales, augmentant la richesse allélique des portées et permettant à la sélection sexuelle post-copulatoire d'avoir lieu. De plus, nous avons pu observer que les animaux les plus hétérozygotes survivent mieux face à une infection bactérienne, probablement via une meilleure tolérance. Les individus les plus hétérozygotes sont également plus gros à âge équivalent, ce qui revêt une importance particulière pour les femelles puisqu'une grande taille leur confère une meilleure fécondité. Ces résultats suggèrent que divers mécanismes sont à l'origine du maintien de la diversité génétique dans les populations d'A. vulgare et confèrent aux individus une meilleure valeur sélective. Ainsi les populations de cet isopode terrestre possèdent vraisemblablement un potentiel adaptatif important permettant leur maintien à long terme. / Genetic diversity is a crucial parameter for both populations and individuals. As such, heterozygosity often confers a selective advantage to individuals in numerous taxa, and sexual selection processes can result in an optimisation of offspring heterozygosity. We tested these hypotheses in the terrestrial isopod Armadillidium vulgare. In this work, we highlighted a higher reproductive success for more heterozygous males, which could result from both intrasexual competition and mate choice, as well as a choice for a genetically dissimilar partner. These two processes result in an increase in offspring heterozygosity. Moreover, we described for the first time a high rate of multiple paternity in natural as well as in experimental populations, increasing brood allelic richness and allowing post-copulatory sexual selection processes. Besides, we showed that more heterozygous individuals survive better when confronted to a bacterial infection, probably through a better tolerance. More heterozygous individuals are also bigger at the same age, which is particularly important in females because a big size leads to a higher fecundity. These results suggest that various mechanisms result in genetic diversity maintenance in A. vulgare populations and confer a better fitness to individuals. Thereby, it is likely that populations of this terrestrial isopod possess a high adaptive potential enabling their long-term maintenance.

Existe grande interesse na determinação das bases genéticas do carcinoma basocelular (CBC) que expliquem seu fenótipo pouco agressivo e comportamento metastático infreqüente. Investigamos a instabilidade de microssatélites (MSI) e perda de heterozigosidade (LOH) nos microssatélites D6S251 (6q14) e D6S252 (6q16) de CBCs esporádicos de alto e baixo risco histológico através da análise de bandas obtidas pelo gel de poliacrilamida após PCR em comparação com o tecido normal. Não houve alteração do microssatélite D6S252 nas 15 amostras estudadas. Para o microssatélite D6S251, houve alterações em 6 das 26 amostras estudadas (23,07%). MSI e LOH ocorreram em 46,15% das amostras de alto risco (respectivamente 15,38% e 30,76), o que sugere o provável envolvimento da região 6q14 na diferenciação histológica do CBC / A lot of interest lies in determining the genetic basis of basal cell carcinoma (BCC) to explain the lack of aggressive phenotype and infrequent metastatic behavior. We have analyzed the microsatellite instability (MSI) and loss of instability (LOH) in the D6S251 (6q14) and D6S252 (6q16) microsatellites patterns of histological low- high-risk sporadic BCC tumor samples using PCR-based assay in comparison with normal tissue. We have not found any alteration in D6S252 microsatellite 15 samples studied. We have encountered D6S251 alterations in 6 of 26 BCC samples (23.07%).MSI and LOH occurred in 46.15% of high-risk samples (15.38% and 30.76%), These results probably suggests participation of 6q14 region in histological differentiation of BCC

Aproximadamente 80% dos casos com Neoplasia endócrina múltipla tipo 1 (NEM1) possuem mutações germinativas no gene supressor de tumor MEN1, que os predispõem a tumores nas glândulas paratireóides, pâncreas endócrino e hipófise, além de outros tumores não endócrinos. A tumorigênese dos mais de 20 diferentes tipos de neoplasias já descritas na NEM1 ocorre pela presença da mutação germinativa MEN1 associadas a um segundo evento mutacional nas células desses tecidos, levando à perda de heterozigose (LOH) do locus do gene MEN1 (11q13) e à inativação da proteína supressora de tumor codificada por esse gene, a proteína MENIN. Recentemente, mutações germinativas em outros genes foram descritas em casos com NEM1 sem mutações no gene MEN1. Esses novos genes (CDKN1A, CDKN1B, CDNK2B e CDKN2C) codificam proteínas envolvidas no controle do ciclo celular (p21, p27, p15 e p18), chamadas proteínas inibidoras de quinases dependentes de ciclinas. Outro gene, chamado AIP, que codifica uma proteína chaperona de mesmo nome, também foi recentemente descrito associado à NEM1. Esses trabalhos descreveram o papel desses novos genes na NEM1, em nível germinativo, entretanto não esclareceu se esses novos genes estão inativados nos tumores de pacientes com NEM1 com mutação MEN1. O presente estudo investigou, pela primeira vez, o status somático do gene p27Kip1 em pacientes com mutação MEN1 e identificou quatro possíveis perda de heterozigose (LOH) em tumores de paratireóides e pâncreas, sugerindo que além de 11q13LOH, os tumores NEM1 podem sofrer raras perdas adicionais do gene supressor tumoral p27Kip1. Essas são as primeiras evidências na literatura de um processo de tumorigênese multi-step na NEM1, envolvendo três eventos genéticos: 1- Mutação germinativa MEN1; 2- 11q13-LOH; 3- Perda somática do gene supressor de tumor p27Kip1/CDKN1B / Approximately 80% of cases with multiple endocrine neoplasia type 1 (MEN1) harbor a germline mutation in the tumor suppressor gene MEN1, which predisposes these patients to tumors comprehending the parathyroid and pituitary glands, endocrine pancreas and others non-endocrine tumors. The tumorigenesis of the more than 20 different types of tumors already described in the MEN1 syndrome occurs due to a MEN1 germline mutation associated with a second mutational event in the cells of these tissues, leading to loss of heterozygosity (LOH) of the MEN1 gene locus (11q13) and therefore inactivation of tumor suppressor protein encoded by this gene, MENIN protein. Recently, germline mutations in other genes have been described in cases with MEN1 without any detectable mutations in the MEN1 gene. These novel genes (CDKN1A, CDKN1B, CDNK2B and CDKN2C) encode proteins involved in the control of the cell cycle (p21, p27, p15 and p18), called cyclin dependent kinases inhibitors. Another gene, called AIP, which encodes a chaperon protein with the same name, was recently described associated with MEN1 phenotypes. These data described a role for these novel genes in the germline level, however whether they are inactivated in tumors of patients with MEN1 mutation is so far not clarified. The present study investigated for the first time, the somatic status of p27KIP1 gene mutation in patients with MEN1 and identified four possible loss of heterozygosity (LOH) in tumors of the parathyroid and pancreas, suggesting that in addition 11q13-LOH, MEN1 tumors may suffer rare loss additional tumor suppressor gene p27KIP1. These are the first evidence in the literature of a process of tumorigenesis in MEN1 multi-step, involving three genetic events: 1-MEN1germlinemutation; 2-11q13LOH; 3-Loss of somatic tumor suppressor gene p27Kip1/CDKN1B

A instabilidade genômica tem sido amplamente usada para caracterizar células cancerosas. Alterações genéticas em queratose actínica (QA) e carcinoma espinocelular (CEC) foram investigadas pelo método de random amplified polymorphic DNA (RAPD) e análise de microssatélites com o objetivo de encontrar marcadores moleculares para auxiliar o prognóstico e o diagnóstico médico. O DNA foi obtido de pacientes brasileiros cirurgiados e tratados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, totalizando oito QAs, 24 CECs, e tecidos normais e/ou leucócitos correspondentes. Os microssatélites estudados foram D6S251, D6S252, D9S15, D9S50, D9S52, D9S180, D9S196, D9S280 e D9S287, tendo em vista a detecção de instabilidade genômica representada por perda de heterozigosidade (LOH) e instabilidade de microssatélites (MSI). Os \"primers\" usados para comparar os padrões de RAPD foram OPA-2, OPA-7, OPA-13, OPA-17, OPB-8, OPB-13, OPB-17 e OPB-19. Foi obtida correlação significativa na progressão de QA (1/8) para CEC (5/22) referente ao microssatélite D6S251. As diferenças nos padrões de DNA obtidos pelo método RAPD comparados aos controles foram maiores em lesões com maior grau de severidade segundo critério histológico. O mesmo padrão RAPD foi observado no controle e no tumor em 27% QA, 24% CEC I, 9% CEC II e 0% CEC III. Estes resultados mostram que o microssatélite D6S251 e o método de RAPD são informativos, podendo ser potenciais candidatos para auxílio no diagnóstico e prognóstico de QA e CEC. / Genomic instability has been widely used to characterize cancer cells. Genetic alterations in human actinic keratosis (AK) and squamous cell carcinomas (SCC) were investigated by the random amplified polymorphic DNA (RAPD) method, and microsatellite analysis. DNA was obtained from Brazilian patients diagnosed and treated in the School of Medicine of University of Sao Paulo out Clinics Hospital. Eight AKs, 24 SCCs, and 4 BCCs, matched to normal skin tissue and/or leukocytes were studied. Microsatellite patterns were obtained with primers specific to amplify D6S251, D6S252, D9S15, D9S50, D9S52, D9S180, D9S196, D9S280, and D9S287, in search of detection Loss of heterozygosity (LOH) and Microsatellite instability (MSI). The RAPD primers were: OPA-2, OPA-7, OPA-13, OPA-17, OPB-8, OPB-13, OPB-17, and OPB-19. A significant correlation was obtained regarding the progress of AK (1/8) to SCC (5/22) detected with the D6S251 microsatellite. DNA fingerprint obtained with RAPD primers were altered in increasing number of samples, according to their histological degree of differentiation. Similar RAPD patterns were observed in tumor and control in 27% AK, 24% SCC I, 9% SCC II, and zero SCC III. These results suggest microsatellite D6S251 and RAPD method to be potential tools in diagnosis and prognosis of AK and SCC.

O lúpus eritematoso sistêmico (LES) é uma doença autoimune com forte componente genético, caracterizada por inflamação crônica e produção de autoanticorpos. O objetivo deste trabalho foi determinar o perfil de variação no número de cópias (CNVs) e de regiões de perda de heterozigose (LOH) na patogênese do LES. A detecção de CNVs e LOH foi feita pela metodologia Cytoscan HD array em pacientes com LES (n = 23) e indivíduos saudáveis (n = 110). Devido à formação tri-híbrida da população brasileira, foi desenvolvido e validado um painel de 345 marcadores informativos de ancestralidade, a partir dados provenientes do próprio array, para estimar as proporções de ancestralidade individual e, em última instância, inseri-las nos modelos de regressão logística como variável de controle nas análises de distribuição de CNVs e LOH. O perfil de CNVs evidenciou que o número e o tamanho de duplicações são maiores nos indivíduos saudáveis do que nos pacientes com LES. Duplicações nos genes FCGR3B e ADAM3A foram descritas como fator de proteção ao LES, quando tais genes foram avaliados por PCR quantitativa em maior grupo amostral de pacientes (n = 135) e controles (n = 200). Além disso, mostrou-se o efeito sinérgico da presença da deleção em ambos os loci FCGR3B e ADAM3A no aumento do risco para desenvolver a doença. Deleções em pacientes com LES envolvendo os genes CFHR4, CFHR5 e HLA-DPB2, previamente descritos em associação com o LES na literatura, foram identificadas por array e confirmadas por PCR digital. O protocolo desenvolvido para identificação de variantes raras, resultou em um conjunto de 21 CNVs raras em pacientes com LES. Em relação às regiões de perda de heterozigose, não foram encontradas evidências de que o número médio e a extensão dos segmentos LOH seja diferente entre pacientes e indivíduos saudáveis. No entanto, os cromossomos 6 e 12 em pacientes exibem regiões de perda de heterozigose em maior quantidade e tamanho do que os de indivíduos saudáveis, além de apresentarem 17 segmentos LOH restritos ao grupo de pacientes com LES. Os resultados aqui descritos evidenciam que novos loci de susceptibilidade ao LES podem ser encontrados quando a distribuição de CNVs é analisada em todo o genoma, em que a investigação de sua relação com a patogênese pode contribuir para a compreensão da base genética da doença. / Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic background characterized by chronic inflammation and autoantibody production. The purpose of this study was to determine the copy number variation (CNV) and loss of heterozygosity (LOH) profiles in the susceptibility to SLE. The detection of CNVs and LOH was performed by the Cytoscan HD array methodology in SLE patients (n = 23) and healthy subjects (n = 110). Due to the tri-hybrid composition of the Brazilian population, a panel of 345 ancestral informative markers was developed and validated, based on data from the array itself, to estimate the proportions of individual ancestry and, ultimately, to insert them into the logistic regression models as a control variable in the analysis of CNV and LOH distribution. The CNVs profile showed that the burden and the size of duplications are higher in healthy individuals than in SLE patients. Duplications in FCGR3B and ADAM3A genes were described as a protective factor for SLE, when these genes were evaluated by quantitative PCR in a larger SLE (n = 135) and control (n = 200) groups. In addition, the synergistic effect of the presence of deletion in both FCGR3B and ADAM3A loci increase the risk of developing the disease. Deletions in SLE patients encompassing the CFHR4, CFHR5 and HLA-DPB2 genes, previously described in the literature in association to SLE, were identified by the array and confirmed by droplet digital PCR. The pipeline developed here for the identification of rare variants resulted in a set of 21 rare CNVs in SLE patients. Regarding the loss of heterozygosity regions, no evidence was found that the mean number and extent of LOH segments is different between patients and healthy individuals. However, the chromosomes 6 and 12 in SLE patients exhibit greater quantity and size of LOH than those of healthy individuals, besides showing 17 LOH segments restricted to the group of SLE. The results described here show that novel susceptibility loci to SLE can be found once the distribution of variants is analyzed throughout the genome, in which the investigation of its relation to the pathogenesis may contribute to the understanding of the genetic basis of the disease.

Abstract Parasites are an inseparable part of the life of wild birds. They may cause morbidity, mortality or reduction in fecundity. Parasite distribution in hosts is typically not uniform and many host factors (e.g. age) may affect the pattern of distribution. Under certain conditions, parasites even have the potential to regulate the host population. The grouse species of Finnish forests — the capercaillie Tetrao urogallus , the black grouse Lyrurus tetrix and the hazel grouse Tetrastes bonasia — harbour several species of intestinal helminth parasites. The populations have fluctuated in cyclic manner but the mechanisms behind the cycles are largely unknown. I studied the interactions of forest grouse and their intestinal helminth parasites by using intestinal samples collected by hunters in five game management districts during eight years (1995–2002). The most common parasite species in the samples was the nematode Ascaridia compar. Also, three species of cestodes (Skrjabinia cesticillus, Paroniella urogalli and Hymenolepis sp.) were found. Large size, male gender and age over 1 year were connected with an increased probability and intensity of A. compar infection. Juvenile grouse were commonly infected with cestodes while in adults infections were quite rare. The influence of inbreeding on the susceptibility to parasite infections was studied in the capercaillie by analysing microsatellite heterozygosity. The less heterozygous birds were more likely to be infected with A. compar and were more intensely infected suggesting negative influence of inbreeding on parasite resistance. An indirect negative effect of parasites was found by comparing bags hunted with a trained dog or without a dog. Grouse infected by cestodes were significantly more common in the dog-assisted bag. Thus, cestode infection seemed to make grouse more vulnerable to canine predation. The interaction between grouse population dynamics and parasites was studied by analyzing the grouse densities obtained from annual wildlife counts and parasite indices. A. compar was most common and most abundant in the years of grouse population decline. The grouse population growth rate was negatively correlated with the annual mean abundance of A. compar. Relative survival but not breeding success decreased as the abundance of A. compar increased. The findings suggest that A. compar influences the dynamics of Finnish grouse even though regular cyclic dynamics are no longer evident. / Tiivistelmä Loiset kuuluvat erottamattomana osana luonnonvaraisten lintujen elämään. Ne voivat aiheuttaa sairautta, kuolleisuutta tai hedelmällisyyden alentumista. Tyypillisesti loiset ovat levinneet isäntäpopulaatioon epätasaisesti ja monet isännän ominaisuudet (esim. ikä) vaikuttavat levinneisyyteen. Tietyissä oloissa loiset voivat jopa säädellä isäntäpopulaatiotaan. Suomalaiset metsäkanalinnut — metso Tetrao urogallus, teeri Lyrurus tetrix ja pyy Tetrastes bonasia — ovat useiden suolistoloismatolajien isäntiä. Metsäkanapopulaatiot ovat vaihdelleet syklisesti, mutta syklejä aiheuttavat mekanismit ovat yhä tuntemattomia. Tutkin metsäkanalintujen ja niiden suolistoloisten välisiä vuorovaikutuksia käyttäen metsästäjien vuosina 1995–2002 viidestä eri riistanhoitopiiristä keräämiä suolistonäytteitä. Yleisin loislaji näytteissä oli kanalintusuolinkainen, Ascaridia compar. Myös kolme heisimatolajia (Skrjabinia cesticillus, Paroniella urogalli ja Hymenolepis sp.) todettiin. Suuri koko, koirassukupuoli ja yli yhden vuoden ikä olivat yhteydessä suurempaan kanalintusuolinkaistartunnan todennäköisyyteen ja voimakkuuteen. Nuorilla (alle 1 v.) linnuilla heisimadot olivat yleisiä, kun taas aikuisilla tartunnat olivat varsin harvinaisia. Sisäsiittoisuuden vaikutusta loistartuntaherkkyyteen tutkittiin metsolla mikrosatelliittiheterotsygotian perusteella. Vähemmän heterotsygoottiset metsot olivat todennäköisemmin ja voimakkaammin suolinkaisten infektoimia, mikä viittaa sisäsiittoisuuden negatiiviseen vaikutukseen loisten vastustuskykyyn. Loisten epäsuora haitallinen vaikutus havaittiin, kun verrattiin koiran kanssa ja ilman koiraa metsästettyä lintusaalista. Heisimadot olivat selvästi yleisempiä linnuilla, jotka oli metsästetty koiran kanssa kuin ilman koiraa metsästetyillä. Heisimatotartunta näytti siis altistavan metsäkanoja koiraeläinten saalistukselle. Metsäkanalintu- ja loispopulaatioiden välistä vuorovaikutusta tutkittiin analysoimalla vuosittaisia metsäkanatiheyksiä ja loisten runsautta. Kanalintusuolinkainen oli yleisimmillään ja runsaimmillaan metsäkanatiheyden laskuvuosina. Metsäkanapopulaation vuosittainen kasvuvauhti korreloi negatiivisesti kanalintusuolinkaisen vuosittaisen runsauden kanssa. Suhteellinen elossasäilyvyys laski kanalintusuolinkaisen runsauden lisääntyessä, mutta lisääntymistuloksen suhteen ei ollut samaa ilmiötä. Löydökset viittaavat siihen, että kanalintusuolinkaisella on vaikutusta suomalaisten metsäkanalintukantojen vaihteluihin, vaikka syklisiä kannanvaihteluja ei enää havaitakaan.

No description available.

The evolution of extra-group paternity (EGP) is a contentious issue in evolutionary biology. This thesis examines the factors and adaptive benefits driving EGP in a high-density, group-living population of European badgers (Meles meles). To improve power to assign parentage, I isolated and characterised 21 new polymorphic microsatellite markers. I genotyped 83% of 1410 badger trapped 1987‒2010 using 35 autosomal microsatellite markers. Maternity and paternity were assigned at 80% confidence ca. 82% of individuals. 48% of paternities were extra-group, where 85% were attributable to neighbouring-group males and EGP was detected in 47% of litters; thus badger social group do not correspond with a breeding unit. I tested whether indirect genetic benefits explain these high EGP rates. (1) ‘Good-gene-as-heterozygosity Hypothesis’: Paternal heterozygosity, but not maternal or an individual’s own heterozygosity, associated positively with first-year survival probability. Under benign environmental conditions, cubs fathered by more heterozygous males had a higher first year survival probability. Despite this correlation, the EGP rate per litter correlated with neither average nor maximum within-group heterozygosity of candidate fathers. (2) Fitness benefit Hypothesis: Extra-group offspring (EGO) had lower first-year survival probability and lived 1.3 years less than within-group offspring (WGO). Female WGO produced more litters and offspring over their lifetime than female EGO, whereas male EGO produced more offspring than male WGO. (3) Inbreeding avoidance hypothesis: The EGP rate within a litter increased with greater average pair-wise relatedness between mothers and within-group candidate fathers. No inbreeding depression on first-year survival probability was detected, but small sample sizes limited statistical power. Socio-ecologically, at the litter level, EGP correlated negatively with the number of within-group candidate fathers, and positively with neighbouring-group candidate fathers. In conclusion, EGP in badgers may reduce inbreeding and be maintained in the population through a sex-specific antagonistic selection and indirect genetic benefits may occur when the total fitness benefits of producing extra-group sons outweigh the costs of producing extra-group daughters. These indirect genetic benefits only partially explain the evolution of promiscuity in European badgers, highlighting that evolutionary factors underlying promiscuity remain unclear.