Polymorphism, inter-population and inter-specific variation in Nyssomyia intermedia (Lutz & Neiva) and Nyssomyia neivai (Pinto) (Diptera, Psychodidae, Phlebotominae)

Nyssomyia intermedia (Lutz & Neiva) and Nyssomyia neivai (Pinto) are morphologically very close and both present great variation in some structures. The objective of this study is a description of the variation among the females of these species in populations from the States of Minas Gerais and São Paulo. The morphological structures studied were the number of horizontal teeth in the cibarium and the number of rings and the shape of the terminal knob of the spermathecae. The spermatheca rings are significantly more numerous in N. intermedia than in N. neivai and the simple shape of the terminal knob predominated in both species. Regarding the cibarium, eight to eleven teeth have been found in both species, with up to twelve teeth in the latter. The number of horizontal teeth and the shape of the terminal knob of the spermathecae were variable throughout the populations of both species and all structures were polymorphic in the populations studied.

The HSR on chromosome 1 of the house mouse, Mus domesticus: distribution and frequency in Switzerland.

A total of 357 house mice (Mus domesticus) from 83 localities uniformly distributed throughout Switzerland were screened for the presence of a homogenously staining region (HSR) on chromosome 1. Altogether 47 mice from 11 localities were HSR/+ or HSR/HSR. One sample of 11 individuals all had an HSR/HSR karyotype. Almost all mice with the variant were collected from the Rhone valley (HSR frequency: 61%) and Val Bregaglia (HSR frequency: 81%). For samples from most of the area of Switzerland, the HSR was absent. There was no strong association between the geographic distribution of the HSR and the areas of occurrence of metacentrics. However, at Chiggiogna the HSR was found on Rb (1.3). Possible explanations for the HSR polymorphism are discussed.

Seasonal and spatial species richness variation of dung beetle (Coleoptera, Scarabaeidae s. str.) in the Atlantic Forest of southeastern Brazil

The knowledge on Atlantic Forest scarab beetle fauna is quite limited. This biome is strongly degraded and these insects can be used as bioindicators since they are sensitive to forest destruction and show distinct organizational patterns in forest fragments or in areas that have been deteriorated by human activity. Thus, a study of the Scarabaeidae (sensu stricto) dung beetles fauna that inhabit Serra do Japi, São Paulo, Brazil (23º12'-23º22' S and 46º53'-47º03'W) was carried out; the monthly species richness was analyzed in six areas during one year and the vegetation's structural physiognomy was described. The areas included a conserved and a degraded valley, a northward and a southward hillside, a hilltop, and an area of secondary forest growing under eucalyptus trees. The specimens were collected using four pitfall traps baited with human feces, which remained at each spot during 48 hours. Between September, 1997 and August, 1998, 3524 individuals of 39 species were collected; the most abundant were: Canthidium trinodosum, Eurysternus cyanescens, Uroxys kratochvili, Scybalocanthon nigriceps, Uroxys lata, Canthonella sp., Dichotomius assifer, Deltochilum furcatum, Canthidium sp.2, Canthon latipes, Deltochilum rubripenne, Eurysternus sp., and Dichotomius sp.1. The number of individuals and species was greater in the hot, rainy season, when there was a correlation between the number of species and the mean annual temperature [r²= 0.69; p<0.01]. The lower winter richness was most pronounced in the conserved valley, while richness remained relatively constant in the degraded valley; abundance was much higher in the degraded valley. The cluster analysis showed that the valleys and hillsides are the most similar in relation to species composition and abundance, yet different from the secondary forest with eucalypts and the hilltop.

Extensive gene traffic on the mammalian X chromosome.

Mammalian sex chromosomes have undergone profound changes since evolving from ancestral autosomes. By examining retroposed genes in the human and mouse genomes, we demonstrate that, during evolution, the mammalian X chromosome has generated and recruited a disproportionately high number of functional retroposed genes, whereas the autosomes experienced lower gene turnover. Most autosomal copies originating from X-linked genes exhibited testis-biased expression. Such export is incompatible with mutational bias and is likely driven by natural selection to attain male germline function. However, the excess recruitment is consistent with a combination of both natural selection and mutational bias.

Spatial variation of dung beetle assemblages associated with forest structure in remnants of southern Brazilian Atlantic Forest

ABSTRACT The Brazilian Atlantic Forest is one of the world's biodiversity hotspots, and is currently highly fragmented and disturbed due to human activities. Variation in environmental conditions in the Atlantic Forest can influence the distribution of species, which may show associations with some environmental features. Dung beetles (Coleoptera: Scarabaeinae) are insects that act in nutrient cycling via organic matter decomposition and have been used for monitoring environmental changes. The aim of this study is to identify associations between the spatial distribution of dung beetle species and Atlantic Forest structure. The spatial distribution of some dung beetle species was associated with structural forest features. The number of species among the sampling sites ranged widely, and few species were found in all remnant areas. Principal coordinates analysis indicated that species composition, abundance and biomass showed a spatially structured distribution, and these results were corroborated by permutational multivariate analysis of variance. The indicator value index and redundancy analysis showed an association of several dung beetle species with some explanatory environmental variables related to Atlantic Forest structure. This work demonstrated the existence of a spatially structured distribution of dung beetles, with significant associations between several species and forest structure in Atlantic Forest remnants from Southern Brazil.

Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats.

We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers.

Broad-scale adaptive genetic variation in alpine plants is driven by temperature and precipitation.

Identifying adaptive genetic variation is a challenging task, in particular in non-model species for which genomic information is still limited or absent. Here, we studied distribution patterns of amplified fragment length polymorphisms (AFLPs) in response to environmental variation, in 13 alpine plant species consistently sampled across the entire European Alps. Multiple linear regressions were performed between AFLP allele frequencies per site as dependent variables and two categories of independent variables, namely Moran's eigenvector map MEM variables (to account for spatial and unaccounted environmental variation, and historical demographic processes) and environmental variables. These associations allowed the identification of 153 loci of ecological relevance. Univariate regressions between allele frequency and each environmental factor further showed that loci of ecological relevance were mainly correlated with MEM variables. We found that precipitation and temperature were the best environmental predictors, whereas topographic factors were rarely involved in environmental associations. Climatic factors, subject to rapid variation as a result of the current global warming, are known to strongly influence the fate of alpine plants. Our study shows, for the first time for a large number of species, that the same environmental variables are drivers of plant adaptation at the scale of a whole biome, here the European Alps.

Prediction of 18-month survival in patients with primary myelodysplastic syndrome. A regression model and scoring system based on the combination of chromosome findings and the Bournemouth score.

The predictive potential of six selected factors was assessed in 72 patients with primary myelodysplastic syndrome using univariate and multivariate logistic regression analysis of survival at 18 months. Factors were age (above median of 69 years), dysplastic features in the three myeloid bone marrow cell lineages, presence of chromosome defects, all metaphases abnormal, double or complex chromosome defects (C23), and a Bournemouth score of 2, 3, or 4 (B234). In the multivariate approach, B234 and C23 proved to be significantly associated with a reduction in the survival probability. The similarity of the regression coefficients associated with these two factors means that they have about the same weight. Consequently, the model was simplified by counting the number of factors (0, 1, or 2) present in each patient, thus generating a scoring system called the Lausanne-Bournemouth score (LB score). The LB score combines the well-recognized and easy-to-use Bournemouth score (B score) with the chromosome defect complexity, C23 constituting an additional indicator of patient outcome. The predicted risk of death within 18 months calculated from the model is as follows: 7.1% (confidence interval: 1.7-24.8) for patients with an LB score of 0, 60.1% (44.7-73.8) for an LB score of 1, and 96.8% (84.5-99.4) for an LB score of 2. The scoring system presented here has several interesting features. The LB score may improve the predictive value of the B score, as it is able to recognize two prognostic groups in the intermediate risk category of patients with B scores of 2 or 3. It has also the ability to identify two distinct prognostic subclasses among RAEB and possibly CMML patients. In addition to its above-described usefulness in the prognostic evaluation, the LB score may bring new insights into the understanding of evolution patterns in MDS. We used the combination of the B score and chromosome complexity to define four classes which may be considered four possible states of myelodysplasia and which describe two distinct evolutional pathways.

Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance.

The identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected. We identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.

Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification.

BACKGROUND: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. METHODS: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. RESULTS: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P=0.04). A significant correlation (P=0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS=46% vs 75%, P=0.023; OS=66.8% vs 100%, P=0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P=0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P=0.018). CONCLUSIONS: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.

Nestling barn owls assess short-term variation in the amount of vocally competing siblings.

Assessing the amount of rivals is crucial to optimally adjust investment into a contest. If laboratory animals show numerical abilities, little is known about the ecological implications particularly in young animals. The two to nine barn owl (Tyto alba) siblings vocally compete for priority of access to food resources before parents actually deliver them. In dyads, the individual that vocalizes at the highest rate in the absence of parents deters its siblings from competing for next delivered prey. We tested the novel hypothesis that to optimally adjust vocal investment, barn owl nestlings assess how many of their siblings are currently competing. To singleton owlets, we broadcasted a fixed global number of calls emitted by one, two or four pre-recorded unfamiliar nestlings. We could thus distinguish the independent effect on singletons' vocal behavior of the global number of calls produced by a brood from the number of competitors that produced these calls. Overall, nestlings retreated more from vocal contest when facing more competitors. However, in front of one highly motivated competitor, nestlings refrained from vocalizing to a larger extent than when competing against more but less motivated individuals. Therefore, young animals assess variation in the number of currently competing siblings based on individual-specific vocal cues.

Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.

Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.

Prominent use of distal 5' transcription start sites and discovery of a large number of additional exons in ENCODE regions.

This report presents systematic empirical annotation of transcript products from 399 annotated protein-coding loci across the 1% of the human genome targeted by the Encyclopedia of DNA elements (ENCODE) pilot project using a combination of 5' rapid amplification of cDNA ends (RACE) and high-density resolution tiling arrays. We identified previously unannotated and often tissue- or cell-line-specific transcribed fragments (RACEfrags), both 5' distal to the annotated 5' terminus and internal to the annotated gene bounds for the vast majority (81.5%) of the tested genes. Half of the distal RACEfrags span large segments of genomic sequences away from the main portion of the coding transcript and often overlap with the upstream-annotated gene(s). Notably, at least 20% of the resultant novel transcripts have changes in their open reading frames (ORFs), most of them fusing ORFs of adjacent transcripts. A significant fraction of distal RACEfrags show expression levels comparable to those of known exons of the same locus, suggesting that they are not part of very minority splice forms. These results have significant implications concerning (1) our current understanding of the architecture of protein-coding genes; (2) our views on locations of regulatory regions in the genome; and (3) the interpretation of sequence polymorphisms mapping to regions hitherto considered to be "noncoding," ultimately relating to the identification of disease-related sequence alterations.

Similarities and differences in altitudinal versus latitudinal variation for morphological traits in Drosophila melanogaster.

Understanding how natural environments shape phenotypic variation is a major aim in evolutionary biology. Here, we have examined clinal, likely genetically based variation in morphology among 19 populations of the fruit fly (Drosophila melanogaster) from Africa and Europe, spanning a range from sea level to 3000 m altitude and including locations approximating the southern and northern range limit. We were interested in testing whether latitude and altitude have similar phenotypic effects, as has often been postulated. Both latitude and altitude were positively correlated with wing area, ovariole number, and cell number. In contrast, latitude and altitude had opposite effects on the ratio between ovariole number and body size, which was negatively correlated with egg production rate per ovariole. We also used transgenic manipulation to examine how increased cell number affects morphology and found that larger transgenic flies, due to a higher number of cells, had more ovarioles, larger wings, and, unlike flies from natural populations, increased wing loading. Clinal patterns in morphology are thus not a simple function of changes in body size; instead, each trait might be subject to different selection pressures. Together, our results provide compelling evidence for profound similarities as well as differences between phenotypic effects of latitude and altitude.

A non-random chromosome abnormality found in precursor-B lineage acute lymphoblastic leukaemia: dic(9;20)(p1?3;q11).

A comparison of cytogenetical data on acute lymphoblastic leukaemia studied at four large European centres has revealed a non-random dicentric chromosome abnormality: dic(9;20) (p1?3;q11) in 10 patients, nine of whom were children. All had early precursor-B lineage ALL, and eight children had a non-standard risk clinical presentation. The origin of the dicentric chromosome was demonstrated using a range of chromosome banding techniques. This was confirmed by FISH using paints and centromeric probes for chromosomes 9 and 20, together with a number of cosmid probes. The follow-up time of these patients is presently too short and the number of patients too few to determine the prognostic significant of this chromosome abnormality.