Selection on age at first and at last reproduction in the long-lived Alpine Swift Apus melba

The way an organism spreads its reproduction over time is defined as a life-history trait, and selection is expected to favour life-history traits associated with the highest fitness return. We use a long-term dataset of 277 life histories to investigate the shape and strength of selection acting on the age at first reproduction and at last reproduction in the long-lived Alpine Swift. Both traits were under strong directional selection, but in opposite directions, with selection favouring birds starting their reproductive career early and being able to reproduce for longer. There was also evidence for stabilising selection acting on both traits, suggesting that individuals should nonetheless refrain from reproducing in their first 2 years of life (i.e. when inexperienced), and that reproducing after 7 years of age had little effect on lifetime fitness, probably due to senescence.

Winter habitat selection by two sympatric forest grouse in western Switzerland: implications for conservation

Two endangered tetraonids, the capercaillie (Tetrao urogallus) and the hazel grouse (Bonasa bonasia rupestris), are sympatric throughout part of their distribution range in central Europe. Precise information on their specific habitat requirements is needed if the coexistence of both species in exploited forests is to be maintained. We quantified winter habitat selection for both species in the upper part (1100-1600 m) of the Jura mountains (Switzerland). No preference for altitude or exposure could be detected. Capercaillie preferred open forests (including grazed forests) with a sparse canopy dominated by spruce (Picea abies) and fir (Abies alba), and avoided dense undercanopy and understorey, especially when dominated by spruce and beech (Fagus sylvatica). By contrast, hazel grouse preferred feeding sites with a dense understorey of rowan (Sorbus aucuparia), willow (Salix sp.), beech and spruce. These preferences can be related to the feeding habits and predator avoidance behaviour of both species. Coexistence thus requires a mosaic distribution of habitat types, with a matrix of open forests (30% canopy cover) where fir is favoured, and understorey kept sparse (20%). Group-cuts of mature trees should allow regeneration patches, where a dense understorey (50% cover) should provide suitable habitats for hazel grouse

Development of physiological resistance and its stage specificity in Culex quinquefasciatus after selection with deltamethrin in Assam, India

The study investigated the development and stage specificity of physiological resistance to insecticides in a colony of Culex quinquefasciatus Say (Diptera: Culicidae) mosquitoes, which are vectors of bancroftian filariasis in India, after selection with deltamethrin. Resistance was selected by exposing the larvae to the concentration of deltamethrin that caused 50% mortality in the tested population (i.e., LC50). Under continuous selection pressure, the LC50 increased steadily in subsequent generations. The estimated LC50 for the F0 generation was 0.409 μg/L; the LC50 first displayed a substantial increase in the F5 generation (5.616 μg/L) and reached 121.902 μg/L in the F10 generation. The objective of this study was to establish a deltamethrin-resistant colony to develop a research programme that will study the evolution of physiological resistance patterns and stage-specific resistance responses in Cx. quinquefasciatus larvae and adults under laboratory conditions. An approximately 298-fold increase in resistance was recorded after 10 generations, as evidenced by the resistance ratio (RR50). The progress and effect of the selection pressure in the adult stage was monitored with the World Health Organisation (WHO) diagnostic test. The mortality, as observed using the WHO diagnostic test, declined significantly from the F5 generation (85%) onwards and the highest rate of survival (65%) was observed in the F10 generation.

In Vivo Selection of Fluoroquinolone-Resistant Escherichia coli Isolates Expressing Plasmid-Mediated Quinolone Resistance and Expanded-Spectrum β-Lactamase

A ciprofloxacin-resistant Escherichia coli isolate, isolate 1B, was obtained from a urinary specimen of a Canadian patient treated with norfloxacin for infection due to a ciprofloxacin-susceptible isolate, isolate 1A. Both isolates harbored a plasmid-encoded sul1-type integron with qnrA1 and blaVEB-1 genes. Isolate 1B had amino acid substitutions in gyrase and topoisomerase.

Diarrea crónica refractaria y malabsorción secundaria a hipogammaglobulinemia común variable, infestación crónica por giardia lambila y gastrectomía total por adenocarcinoma gástrico: un manejo nutricional complejo

Gastric cancer is a frequent cause of cancer-related mortality in the world. Surgery is the only potentially curative therapy, although the adverse effects of surgery are common and considerable. Common variable immunodeficiency is in many cases cause of gastrointestinal system problems such as chronic diarrhea caused by infestation with giardia lamblia, nodular lymphoid hiperplasia ad loss of villi leading frequently to malapsortion and malnutrition. Nutritional deficiencies due to malapsorption (postgastrectomy and secondary to loss of villi, giardiasis and common variable inmunodeficiency) are common. We present the case of a patient with gastric cancer who underwent a gastrectomy with common variable hipogammaglobulinemia and chronic infestation by giardia lamblia, with serious diarrhea resistant to treatment and malabsorption.

Selection on a eumelanic ornament is stronger in the tropics than in temperate zones in the worldwide-distributed barn owl.

Spatial variation in the pattern of natural selection can promote local adaptation and genetic differentiation between populations. Because heritable melanin-based ornaments can signal resistance to environmentally mediated elevation in glucocorticoids, to oxidative stress and parasites, populations may vary in the mean degree of melanic coloration if selection on these phenotypic aspects varies geographically. Within a population of Swiss barn owls (Tyto alba), the size of eumelanic spots is positively associated with survival, immunity and resistance to stress, but it is yet unknown whether Tyto species that face stressful environments evolved towards a darker eumelanic plumage. Because selection regimes vary along environmental gradients, we examined whether melanin-based traits vary clinally and are expressed to a larger extent in the tropics where parasites are more abundant than in temperate zones. To this end, we considered 39 barn owl species distributed worldwide. Barn owl species living in the tropics displayed larger eumelanic spots than those found in temperate zones. This was, however, verified in the northern hemisphere only. Parasites being particularly abundant in the tropics, they may promote the evolution of darker eumelanic ornaments.

Prospective universal application of mycobacterial interspersed repetitive-unit-variable-number tandem-repeat genotyping to characterize Mycobacterium tuberculosis isolates for fast identification of clustered and orphan cases.

The use of molecular tools for genotyping Mycobacterium tuberculosis isolates in epidemiological surveys in order to identify clustered and orphan strains requires faster response times than those offered by the reference method, IS6110 restriction fragment length polymorphism (RFLP) genotyping. A method based on PCR, the mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) genotyping technique, is an option for fast fingerprinting of M. tuberculosis, although precise evaluations of correlation between MIRU-VNTR and RFLP findings in population-based studies in different contexts are required before the methods are switched. In this study, we evaluated MIRU-VNTR genotyping (with a set of 15 loci [MIRU-15]) in parallel to RFLP genotyping in a 39-month universal population-based study in a challenging setting with a high proportion of immigrants. For 81.9% (281/343) of the M. tuberculosis isolates, both RFLP and MIRU-VNTR types were obtained. The percentages of clustered cases were 39.9% (112/281) and 43.1% (121/281) for RFLP and MIRU-15 analyses, and the numbers of clusters identified were 42 and 45, respectively. For 85.4% of the cases, the RFLP and MIRU-15 results were concordant, identifying the same cases as clustered and orphan (kappa, 0.7). However, for the remaining 14.6% of the cases, discrepancies were observed: 16 of the cases clustered by RFLP analysis were identified as orphan by MIRU-15 analysis, and 25 cases identified as orphan by RFLP analysis were clustered by MIRU-15 analysis. When discrepant cases showing subtle genotypic differences were tolerated, the discrepancies fell from 14.6% to 8.6%. Epidemiological links were found for 83.8% of the cases clustered by both RFLP and MIRU-15 analyses, whereas for the cases clustered by RFLP or MIRU-VNTR analysis alone, links were identified for only 30.8% or 38.9% of the cases, respectively. The latter group of cases mainly comprised isolates that could also have been clustered, if subtle genotypic differences had been tolerated. MIRU-15 genotyping seems to be a good alternative to RFLP genotyping for real-time interventional schemes. The correlation between MIRU-15 and IS6110 RFLP findings was reasonable, although some uncertainties as to the assignation of clusters by MIRU-15 analysis were identified.

Prevalent role of TCR alpha-chain in the selection of the preimmune repertoire specific for a human tumor-associated self-antigen.

The specificity of recognition of pMHC complexes by T lymphocytes is determined by the V regions of the TCR alpha- and beta-chains. Recent experimental evidence has suggested that Ag-specific TCR repertoires may exhibit a more V alpha- than V beta-restricted usage. Whether V alpha usage is narrowed during immune responses to Ag or if, on the contrary, restricted V alpha usage is already defined at the early stages of TCR repertoire selection, however, has remained unexplored. Here, we analyzed V and CDR3 TCR regions of single circulating naive T cells specifically detected ex vivo and isolated with HLA-A2/melan-A peptide multimers. Similarly to what was previously observed for melan-A-specific Ag-experienced T cells, we found a relatively wide V beta usage, but a preferential V alpha 2.1 usage. Restricted V alpha 2.1 usage was also found among single CD8(+) A2/melan-A multimer(+) thymocytes, indicating that V alpha-restricted selection takes place in the thymus. V alpha 2.1 usage, however, was independent from functional avidity of Ag recognition. Thus, interaction of the pMHC complex with selected V alpha-chains contributes to set the broad Ag specificity, as underlined by preferential binding of A2/melan-A multimers to V alpha 2.1-bearing TCRs, whereas functional outcomes result from the sum of these with other interactions between pMHC complex and TCR.

Characterization of Mycobacterium tuberculosis Beijing isolates from the Mediterranean area

BACKGROUND. The Beijing lineage of Mycobacterium tuberculosis is causing concern due to its global distribution and its involvement in severe outbreaks. Studies focused on this lineage are mainly restricted to geographical settings where its prevalence is high, whereas those in other areas are scarce. In this study, we analyze Beijing isolates in the Mediterranean area, where this lineage is not prevalent and is mainly associated with immigrant cases. RESULTS. Only 1% (N = 26) of the isolates from two population-based studies in Spain corresponded to Beijing strains, most of which were pan-susceptible and from Peruvian and Ecuadorian patients. Restriction fragment length polymorphism typing with the insertion sequence IS6110 identified three small clusters (2-3 cases). Mycobacterial interspersed repetitive unit-variable number tandem repeat typing (MIRU-15) offered low discriminatory power, requiring the introduction of five additional loci. A selection of the Beijing isolates identified in the Spanish sample, together with a sample of Beijing strains from Italy, to broaden the analysis context in the Mediterranean area, were assayed in an infection model with THP-1 cells. A wide range of intracellular growth rates was observed with only two isolates showing an increased intracellular replication, in both cases associated with contained production of TNF-alpha. No correlation was observed between virulence and the Beijing phylogenetic group, clustered/orphan status, or resistance. The Beijing strain responsible for extensive spread on Gran Canaria Island was also identified in Madrid, but did not lead to secondary cases and did not show high infectivity in the infection model. CONCLUSIONS. The Beijing lineage in our area is a non-homogeneous family, with only certain highly virulent representatives. The specific characterization of Beijing isolates in different settings could help us to accurately identify the virulent representatives before making general assumptions about this lineage.

Intra- and intersexual selection and their potential consequences on fitness-relevant traits in several fish species

Résumé : Les mécanismes de sélection sexuelle, en particulier la compétition entre mâles (sélection inter-sexuelle) et le choix des femelles (sélection intra-sexuelle), peuvent fortement influencer le succès reproducteur d'un individu, c'est-à-dire son nombre de descendants. On observe ainsi que les mâles dominants et les mâles élaborant des caractères sexuels secondaires marqués ont un succès reproducteur élevé. Toutefois, le succès reproducteur ne suffit pas pour garantir une contribution génétique élevée, parce que la fitness dépend également de la performance des descendants (c'est-à-dire de leur survie et de leur propre succès reproducteur). Si cette performance dépend en partie des gènes paternels, les males ont un avantage certain à signaler leur qualité aux femelles afin d'atteindre des taux de reproduction élevé. Ce mécanisme de signalisation est connu sous le nom de 'good genes hypothesis', toutefois très peu d'études ont clairement démontré le lien entre la qualité génétique des individus et la signalisation. De plus, la performance des descendants peut aussi dépendre des effets génétiques de compatibilité entre mâles et femelles ('compatible genes'). C'est-à-dire que certains allèles paternels n'apporteraient un avantage aux descendants qu'en combinaison avec certains allèles maternels. Nous avons déterminé, durant la période de reproduction, le statut de dominance des mâles pour deux espèces de poissons d'eau douce : la truite (Salmo trotta) et le vairon (Phoxinus phoxinus), puis nous avons évalué la relation entre le succès reproducteur et le statut de dominance et/ou la quantité de signalisation des caractères sexuels secondaires. Nous avons également fécondés artificiellement des oeufs de truites et de corégones (Coregonus palaea), en croisant chaque mâle avec chaque femelle (full-factorial breeding design). Ce type de design autorise la quantification précise des effets génétiques et permet de séparer les effets de 'good genes' et de 'compatible genes'. Cela a été fait sous différentes intensités de stress bactérien, ainsi que dans des conditions naturelles, et nous avons pu ainsi tester si certains indicateurs de qualité génétique des mâles ('good genes') étaient liés a) à la dominance et/ou b) à l'expression des caractères sexuels secondaires des mâles comme l'intensité mélanique ou la taille des tubercules sexuels. En outre, nous cherchons à savoir si la survie des descendants est liée à certaines combinaison des gènes du complexe d'histocompatibilité majeur (MHC) et/ou à la parenté génétique des parents, les deux traits étant soupçonnés d'avoir des influences génétique de compatibilité (`compatible genes') à la performance des descendants. Nous avons constaté que la dominance des mâles est directement liée à la taille et au poids des mâles (truites, vairons), mais également aux caractères sexuels secondaires (tubercules). De plus, les mâles vairons dominant ont eu un succès de fécondation plus élevés que les mâles subordonnés. Nous montrons que les truites et corégones mâles diffèrent dans leur qualité génétique, qui a été mesurée avéc la survie embryonnaire, le temps avant l'éclosion et enfin la croissance juvénile. Contrairement aux prédictions, la dominance (ou les traits indicatifs de dominance) n'était liée à la qualité génétique, dans aucun des traitements, et ne fonctionne donc pas comme indicateur de qualité. Par contre, la qualité génétique était liée aux caractères sexuels secondaires, particulièrement par la teinte mélanique chez les truites. Les embryons de truites issus de pères sombres survivaient mieux que ceux issus de pères clairs dans des environnements difficiles, de plus leur croissance était plus élevée lors de leur première année dans des conditions naturelles. La taille des juvéniles lors de leur première année est un trait important lié au succès dans la compétition pour des ressources telles qu'abri ou nourriture. De plus, les femelles truites peuvent augmenter la survie de leurs descendants en choisissant des mâles selon leur type de MHC ou selon leur degré de parenté. En outre, chez les corégones, la morphologie des tubercules sexuels ne semble pas signaler la qualité génétique. Nous avons également remarqué que l'exposition à des pathogènes non-létaux pouvait influencer la performance des alevins à court et long terme, probablement en affaiblissant leur système immunitaire. Cette thèse montre que les mâles diffèrent dans leur qualité génétique et que différents mécanismes de sélection inter- ou intra-sexuelle (par exemple la préférence pour des mâles sombres, pour des génotypes MHC ou pour des couples avec degré de parenté basse) pouvait avoir un effet positif sur la qualité des descendants, bien que cet effet génétique pouvait changer au cours du temps et entre différents environnements. Contrairement à nos attentes, le résultat de la compétition intra-sexuelle (la hiérarchie de dominance entre mâles) n'était pas lié à la qualité génétique individuelle ('good genes'). Dans ce sens, ce travail permet également de contribuer à l'explication du fait que la sélection sexuelle, de par sa forte sélection directionnelle, ne conduit pas à la diminution de la variance génétique, mais plutôt à la maintenance du polymorphisme génétique. Summary : Sexual selection mechanisms, especially male-male competition (inteasexual selection) and female mate choice (inteasexual selection), can strongly influence individual mating success, often resulting in dominant males and males with elaborate secondary sexual characters having higher fertilisation success. However, siring a high number of offspring alone does not guarantee high individual fitness, as fitness does also strongly depend on offspring performance (i.e. survival, fecundity). If this superiority in offspring performance depends on paternally inherited genes, the fathers are expected to signal this potential indirect benefit to females in order to attain high mating rates. This mechanism is also known as the 'good genes' hypothesis of sexual selection but until now most studies failed to conclusively show the relation of an individual genetic quality and its potential signalling traits. Further, offspring performance could also depend on compatible gene effects. These are alleles that increase offspring performance only in combination with other specific alleles. We first determined male dominance status from intrasexual competition during mating season for brown trout (Salmo trutta) and European minnows (Phoxinus phoxinus). For minnows we additionally checked if dominance and/or secondary sexual traits were linked to fertilisation success. Further, we artificially fertilised brown trout and alpine whitefish (Coregonus palaea) eggs, following full factorial breeding designs, enabling to properly measure `good gene' and `compatible gene' effects on offspring performance. This was done under different intensities of natural stressors, as well as under natural conditions. This procedure allowed us to test if the obtained male genetic quality measures (good genes effects) were indicated by a) dominance or lay traits linked to dominance and/or by b) secondary sexual characteristics such as melanin-based male skin darkness or breeding tubercles. Further, we investigated if offspring survival was linked to the MHC (major histocompatibility complex) gene combinations and/or to the parental genetic relatedness, as both traits were shown to have 'compatible gene' effects that may influence offspring performance. We found that male dominance in intrasexual competition was positively linked to body size, body weight (brown trout, minnows) but also to elaborate secondary sexual characteristics (breeding tubercles in minnows). Further, dominant minnow males did have an increased fertilisation success compared to subordinate ones. We show that brown trout and whitefish males do usually differ in their genetic quality, which was measured as embryo survival, hatching timing and finally as juvenile growth. Contrary to prediction male dominance or dominance indicating traits do not function as a quality signal as they were not linked to genetic quality. This result was constant when measuring genetic quality under different levels of natural stressors and under natural conditions (brown trout). On the other hand genetic quality seemed to be indicated by secondary sexual characteristics, specifically by melanin-based skin darkness in brown trout as brown trout embryos sired by darker fathers had increased survival rates when raised under harsh conditions and. they grew larger as juveniles after one year of growth in a natural stream, which is an important trait influencing success of juveniles in competition for hidings, food and other resources. Furthermore, brown trout females may increase the survival of their embryos when choosing males according to their MHC genotypes or to the general genetic relatedness between themselves and their potential mates. In whitefish on the other hand breeding tubercle morphology did not seem to signal genetic quality. Eventually, we saw that anon-lethal exposure to pathogens might influence short term and long term offspring performance probably by weakening an exposed individual's immune system. This thesis shows that males usually differ in their genetic quality and that different inter- or intrasexual selection mechanisms (e.g. mate selection favouring dark males, preference for MHC genotype combinations or for unrelated mates) may have strong positive effects on genetically dependent offspring performance but that such genetìc effects can change over time and environments. In contrast to our a priori expectations, the outcome of intrasexual selection, namely male dominance hierarchies, with dominant males often having high fertilisation success, was not linked to individual genetic quality (`good genes'). In this sense the present thesis may also be a helpful contribution to understand why sexual selection does not lead to rapid loss of genetic variation by strong directional selection but could even lead to the maintenance of genetic variation in natural populations.

Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias.

Background: Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias. Methods: A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and prehospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables. Results: Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93). Conclusion: Pre-hospital oral antibiotherapy appears to reduce IMD mortality.

Spoligotyping and variable number tandem repeat analysis of Mycobacterium bovis isolates from cattle in Brazil

We performed spoligotyping and 12-mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTRs) typing to characterise Mycobacterium bovis isolates collected from tissue samples of bovines with lesions suggestive for tuberculosis during slaughter inspection procedures in abattoirs in Brazil. High-quality genotypes were obtained with both procedures for 61 isolates that were obtained from 185 bovine tissue samples and all of these isolates were identified as M. bovis by conventional identification procedures. On the basis of the spoligotyping, 53 isolates were grouped into nine clusters and the remaining eight isolates were unique types, resulting in 17 spoligotypes. The majority of the Brazilian M. bovis isolates displayed spoligotype patterns that have been previously observed in strains isolated from cattle in other countries. MIRU-VNTR typing produced 16 distinct genotypes, with 53 isolates forming eight of the groups, and individual isolates with unique VNTR profiles forming the remaining eight groups. The allelic diversity of each VNTR locus was calculated and only two of the 12-MIRU-VNTR loci presented scores with either a moderate (0.4, MIRU16) or high (0.6, MIRU26) discriminatory index (h). Both typing methods produced similar discriminatory indexes (spoligotyping h = 0.85; MIRU-VNTR h = 0.86) and the combination of the two methods increased the h value to 0.94, resulting in 29 distinct patterns. These results confirm that spoligotyping and VNTR analysis are valuable tools for studying the molecular epidemiology of M. bovis infections in Brazil.

The stepwise selection for ketoconazole resistance induces upregulation of C14-demethylase (CYP51) in Leishmania amazonensis

Ketoconazole is a clinically safe antifungal agent that also inhibits the growth of Leishmania spp. A study was undertaken to determine whether Leishmania parasites are prone to becoming resistant to ketoconazole by upregulating C14-demethylase after stepwise pharmacological pressure. Leishmania amazonensis promastigotes [inhibitory concentration (IC)50 = 2 µM] were subjected to stepwise selection with ketoconazole and two resistant lines were obtained, La8 (IC50 = 8 µM) and La10 (IC50 = 10 µM). As a result, we found that the resistance level was directly proportional to the C14-demethylase mRNA expression level; we also observed that expression levels were six and 12 times higher in La8 and La10, respectively. This is the first demonstration that L. amazonensis can up-regulate C14-demethylase in response to drug pressure and this report contributes to the understanding of the mechanisms of parasite resistance.

Retroviral Integration Site Selection

The stable insertion of a copy of their genome into the host cell genome is an essential step of the life cycle of retroviruses. The site of viral DNA integration, mediated by the viral-encoded integrase enzyme, has important consequences for both the virus and the host cell. The analysis of retroviral integration site distribution was facilitated by the availability of the human genome sequence, revealing the non-random feature of integration site selection and identifying different favored and disfavored genomic locations for individual retroviruses. This review will summarize the current knowledge about retroviral differences in their integration site preferences as well as the mechanisms involved in this process.

Human genetic selection on the MTHFR 677C>T polymorphism.

BACKGROUND The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA). METHODS A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman probes. A section of our population (n = 276) born in 1980-1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period. RESULTS An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980-1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98. CONCLUSION Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations.