Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes

BACKGROUND: Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS: We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS: We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1x10(-7)). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS: We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype.

Palaeohydrology, fires and vegetation succession in the southern Baltic during the last 7500 years reconstructed from a raised bog based on multi-proxy data

We present the first 7500 yr long multi-proxy record from a raised bog located at the southern Baltic coast, Poland. Testate amoebae, plant macrofossils, pollen and microscopic charcoal were used to reconstruct environmental changes in Pomerania (northern Poland, Kaszuby Lakeland) from a 7-m thick peat archive of Stążki bog dated 5500 BC–AD 1250. We obtained a record of proxies representing different spatial scales: regional vegetation changed simultaneously with local vegetation, and testate amoebae showed a pattern of change similar to that of pollen and plant macrofossils. On the basis of the combined proxies, we distinguished three hydroclimatic stages: moist conditions 5500–3450 BC, drier conditions with regionally increased fires up to 600 BC, and again moist conditions from 600 BC onward. During the drier interval, a first climatic shift to wetter conditions at 1700 BC is indicated by regional pollen as the replacement of Corylus by Carpinus, and locally by, e.g., the increase of Hyalosphenia elegans and mire plants such as Sphagnum sec. Cuspidata. Furthermore, we observed a correlation since 600 BC among the re-expansion of Carpinus (after a sudden decline ca. 950 BC), increased peat accumulation, increase of Hyalosphenia species, and fewer fires, suggesting lower evapotranspiration and a stable high water table in the bog. Fagus started to expand after AD 810 gradually replacing Carpinus, which was possibly due to a gradually more oceanic climate, though we cannot exclude human impact on the forests. Peat accumulation, determined by radiocarbon dating, varied with bog surface wetness. The hydroclimatic phases found in Stążki peatland are similar to moisture changes recorded in other sites from Poland and Europe. This is the first detailed record of hydroclimatic change during the Holocene in the southern Baltic region, so it forms a reference site for further studies on other southern Baltic bogs that are in progress.

Responses to rapid warming at Termination 1a at Gerzensee (Central Europe): Primary succession, albedo, soils, lake development, and ecological interactions

The transition from the Oldest Dryas to the Bølling around 14,685 cal yr BP was a period of extremely rapid climatic warming. From a single core of lake marl taken at Gerzensee (Switzerland) we studied the transition in stable isotopes of oxygen and carbon on bulk sediment and charophyte remains, as well as on monospecific samples of ostracods, after Pisidium a; in addition pollen, chironomids, and Cladocera were analyzed. The δ18O record serves as an estimate of mean air temperature, and by correlation to the one from NGRIP in Greenland it provides a timescale. The timing of responses: The statistically significant zone boundaries of the biostratigraphies are telescoped at the rapid increase of about 3‰ in δ18O at the onset of Bølling. Biotic responses may have occurred within sampling resolution (8 to 16 years), although younger zone boundaries are less synchronous. Gradual and longer-lasting responses include complex processes such as primary or secular succession. During the late-glacial interstadial of Bølling and Allerød, two stronger and two weaker cool phases were found. Biological processes involved in the responses occurred on levels of individuals (e.g. pollen productivity), of populations (increases or decreases, immigration, or extinction), and on the ecosystem level (species interactions such as facilitation or competition). Abiotic and biotic interactions include pedogenesis, nitrogen-fixation, nutrient cycling, catchment hydrology, water chemistry of the lake and albedo (controlled by the transition from tundra to forest). For the Swiss Plateau this major change in vegetation induced a change in the mammal fauna, which in turn led to changes in the tool-making by Paleolithic people.

Secondary succession and dipterocarp recruitment in Bornean rain forest after logging

To understand succession in dipterocarp rain forest after logging, the structure, species composition and dynamics of primary (PF) and secondary (SF) forest at Danum were compared. In 10 replicate 0.16-ha plots per forest type trees >= 10 cm gbh (3.2 cm dbh) were measured in 1995 and 2001. The SF had been logged in 1988, which allowed successional change to be recorded at 8 and 13 years. In 2001, saplings (1.0-3.1 cm dbh) were measured in nested quadrats. The forest types were similar in mean radiation at 2 m height, and in density, basal area and species number of all trees. Among small (10 <= 31.4) and large ( >= 31.4 cm gbh) trees, in both 1995 and 2001, there were 10- and 3-fold more dipterocarps in SF than PF respectively; and averaging over the two dates, there were correspondingly ca. 10- and 18-fold more pioneers. Mortality was ca. 60% higher in SF than PF, largely due to a seven-fold difference for pioneers: for dipterocarps there was little difference. Recruitment was similar in PF and SE Stem growth rates were 37% higher in SF than PF for all trees, although dipterocarps showed the opposite trend. Among saplings, dipterocarps dominated SF with a 10-fold higher density than in PF. For dipterocarps, the light (LH) and medium-heavy (MHH) canopy hardwoods, and the shade-tolerant, smaller-stature other (OTH) species (e.g. Hopea and Vatica) were in the ratios ca. 40:15:45 in SF and 85: < 1:15 in PF. LHs had higher mortality than OTHs in SE In PF ca. 80% of the saplings were LH: in SF ca. 70% were OTH. The predominance of OTHs in SF is explained by the logging of primary rain forest which was in a likely late stage of recovery from natural disturbance, plus the continuing shaded conditions in the understorey promoted by dense pioneer vegetation. At 13 years after logging succession appeared to be inhibited: LHs were being suppressed but MHHs and OTHs persisted. Succession in lowland dipterocarp, rain forests may therefore depend on the successional state of the primary forest when it is logged. A review of logged versus unlogged studies in Borneo highlights the need for more detailed ecological comparisons.

Inheritance of porcine receptors for enterotoxigenic Escherichia coli with fimbriae F4ad and their relation to other F4 receptors.

Enteric Escherichia coli infections are a highly relevant cause of disease and death in young pigs. Breeding genetically resistant pigs is an economical and sustainable method of prevention. Resistant pigs are protected against colonization of the intestine through the absence of receptors for the bacterial fimbriae, which mediate adhesion to the intestinal surface. The present work aimed at elucidation of the mode of inheritance of the F4ad receptor which according to former investigations appeared quite confusing. Intestines of 489 pigs of an experimental herd were examined by a microscopic adhesion test modified in such a manner that four small intestinal sites instead of one were tested for adhesion of the fimbrial variant F4ad. Segregation analysis revealed that the mixed inheritance model explained our data best. The heritability of the F4ad phenotype was estimated to be 0.7±0.1. There are no relations to the strong receptors for variants F4ab and F4ac. Targeted matings allowed the discrimination between two F4ad receptors, that is, a fully adhesive receptor (F4adRFA) expressed on all enterocytes and at all small intestinal sites, and a partially adhesive receptor (F4adRPA) variably expressed at different sites and often leading to partial bacterial adhesion. In pigs with both F4ad receptors, the F4adRPA receptor is masked by the F4adRFA. The hypothesis that F4adRFA must be encoded by at least two complementary or epistatic dominant genes is supported by the Hardy-Weinberg equilibrium statistics. The F4adRPA receptor is inherited as a monogenetic dominant trait. A comparable partially adhesive receptor for variant F4ab (F4abRPA) was also observed but the limited data did not allow a prediction of the mode of inheritance. Pigs were therefore classified into one of eight receptor phenotypes: A1 (F4abRFA/F4acR+/F4adRFA); A2 (F4abRFA/F4acR+/F4adRPA); B (F4abRFA/F4acR+/F4adR-); C1 (F4abRPA/F4acR-/F4adRFA); C2 (F4abRPA/F4acR-/F4adRPA); D1 (F4abR-/F4acR-/F4adRFA); D2 (F4abR-/F4acR-/F4adRPA); E (F4abR-/F4acR-/F4adR-).

Antipredator defences of young are independently determined by genetic inheritance, maternal effects and own early experience in mouthbrooding cichlids.

1. Predation is a prime force of natural selection. Vulnerability to predation is typically highest early in life, hence effective antipredator defences should work already shortly after birth. Such early defences may be innate, transmitted through non-genetic parental effects or acquired by own early experience. 2. To understand potential joint effects of these sources of antipredator defences on pheno- typic expression, they should be manipulated within the same experiment. We investigated innate, parental and individual experience effects within a single experiment. Females of the African cichlid Simochromis pleurospilus were exposed to the offspring predator Ctenochromis horei or a benign species until spawning. Eggs and larvae were hand-reared, and larvae were then exposed to odour cues signalling the presence or absence of predators in a split-brood design. 3. Shortly after independence of maternal care, S. pleurospilus undergo a habitat shift from a deeper, adult habitat to a shallow juvenile habitat, a phase where young are thought to be par- ticularly exposed to predation risk. Thus, maternal effects induced by offspring predators pres- ent in the adult habitat should take effect mainly shortly after independence, whereas own experience and innate antipredator responses should shape behaviour and life history of S. pleurospilus during the later juvenile period. 4. We found that the manipulated environmental components independently affected different offspring traits. (i) Offspring of predator-exposed mothers grew faster during the first month of life and were thus larger at termination of maternal care, when the young migrate from the adult to the juvenile habitat. (ii) The offspring’s own experience shortly after hatching exerted lasting effects on predator avoidance behaviour. (iii) Finally, our results suggest that S. pleuro- spilus possess a genetically inherited ability to distinguish dangerous from benign species. 5. In S. pleurospilus, maternal effects were limited to a short but critical time window, when young undergo a niche shift. Instead, own environmental sampling of predation risk combined with an innate predisposition to correctly identify predators appears to prepare the young best for the environment, in which they grow up as juveniles.

pATOM36 mediates mitochondrial protein import and mitochondrial DNA inheritance

The multisubunit ATOM complex mediates import of essentially all proteins across the outer mitochondrial membrane in T. brucei. Moreover, an additional protein termed pATOM36, which is loosely associated with the ATOM complex, has been implicated in the import of only a subset of mitochondrial matrix proteins. Here we have investigated more precisely which role pATOM36 plays in mitochondrial protein import. RNAi mediated ablation of pATOM36 specifically depletes a subset of ATOM complex subunits and as a consequence results in the collapse of the ATOM complex as shown by Blue native PAGE. In addition, a SILAC-based global proteomic analysis of uninduced and induced pATOM36 RNAi cells together with in vitro import experiments suggest that pATOM36 might be a novel protein insertase acting on a subset of alpha-helically anchored mitochondrial outer membrane proteins. Identification of pATOM36 interaction partners by co-immunoprecipitation together with immunofluorescence analysis furthermore shows that unexpectedly a fraction of the protein is associated with the tripartite attachment complex (TAC). This complex is essential for proper inheritance of the mtDNA; also called kinetoplast or kDNA; as it forms a physical connection between the kDNA and the basal body of the single flagellum throughout the cell cycle. Thus, the presence of pATOM36 in the TAC provides an exciting link between mitochondrial protein import and kDNA inheritance.

Species interactions and random dispersal rather than habitat filtering drive community assembly during early plant succession

Theory on plant succession predicts a temporal increase in the complexity of spatial community structure and of competitive interactions: initially random occurrences of early colonising species shift towards spatially and competitively structured plant associations in later successional stages. Here we use long-term data on early plant succession in a German post mining area to disentangle the importance of random colonisation, habitat filtering, and competition on the temporal and spatial development of plant community structure. We used species co-occurrence analysis and a recently developed method for assessing competitive strength and hierarchies (transitive versus intransitive competitive orders) in multispecies communities. We found that species turnover decreased through time within interaction neighbourhoods, but increased through time outside interaction neighbourhoods. Successional change did not lead to modular community structure. After accounting for species richness effects, the strength of competitive interactions and the proportion of transitive competitive hierarchies increased through time. Although effects of habitat filtering were weak, random colonization and subsequent competitive interactions had strong effects on community structure. Because competitive strength and transitivity were poorly correlated with soil characteristics, there was little evidence for context dependent competitive strength associated with intransitive competitive hierarchies.

Genetic diversity and differentiation follow secondary succession in a multi-species study on woody plants from subtropical China

Aims: Species diversity and genetic diversity may be affected in parallel by similar environmental drivers. However, genetic diversity may also be affected independently by habitat characteristics. We aim at disentangling relationships between genetic diversity, species diversity and habitat characteristics of woody species in subtropical forest. Methods: We studied 11 dominant tree and shrub species in 27 plots in Gutianshan, China, and assessed their genetic diversity (Ar) and population differentiation (F’ST) with microsatellite markers. We tested if Ar and population specific F’ST were correlated to local species diversity and plot characteristics. Multi-model inference and model averaging were used to determine the relative importance of each predictor. Additionally we tested for isolation-by-distance and isolation-by-elevation by regressing pairwise F’ST against pairwise spatial and elevational distances. Important findings: Genetic diversity was not related to species diversity for any of the study species. Thus, our results do not support joint effects of habitat characteristics on these two levels of biodiversity. Instead, genetic diversity in two understory shrubs, Rhododendron simsii and Vaccinium carlesii, was affected by plot age with decreasing genetic diversity in successionally older plots. Population differentiation increased with plot age in Rhododendron simsii and Lithocarpus glaber. This shows that succession can reduce genetic diversity within, and increase genetic diversity between populations. Furthermore, we found four cases of isolation-by-distance and two cases of isolation-by-elevation. The former indicates inefficient pollen and seed dispersal by animals whereas the latter might be due to phenological asynchronies. These patterns indicate that succession can affect genetic diversity without parallel effects on species diversity and that gene flow in a continuous subtropical forest can be restricted even at a local scale.

Family Firm Incumbent’s Attitude toward Intra-family Succession: Antecedents and Effects on Intentions

Research shows that intention for intra-family succession is an important determinant of family firm behavior. To provide a systematic analysis of the antecedents of such intention, we use the theory of planned behavior to model the incumbent leader’s attitude toward intra-family succession because that particular attitude is idiosyncratic to family firms. Empirical tests using a sample of 271 Italian incumbent leaders of family firms show that, as predicted by planned behavior theory, attitude and self-efficacy are significant predictors of intention. They show further that attitude is affected by the number of children, emotional attachment, and need for control.