Mutations and Deletions in PCDH19 Account for Various Familial or Isolated Epilepsies in Females

Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation. © 2010 Wiley-Liss, Inc

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

Les protéines de couche S et le régulon-PlcR de Bacillus anthracis (implications physiologiques et évolutives)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

A modelling analysis of the genetic variation of phenology between tree populations

International audienceThe phenology of temperate woody plants is commonly assumed to be locally adapted to climate. 2 However, the high gene flow expected in forest tree species, the high between year variance of thermal conditions at a given place and the high plasticity of phenology regarding temperature, lead us to hypothesize that genetic variation of phenology between populations is likely to be insignificant for many lowland tree species. 3 Using phenological models, we investigated variation in the timing of flowering between locations for four European clonal tries and between different populations of a further five species. 4 Models were also used to study the responses of the different populations to climate change by simulating transfers of each population to different locations. 5 While clinal variations can be observed in the phenological response to temperature between populations, only one species (Corylus avellana) showed significantly different responses between populations and even then only one of three populations could be separated from the others. 6 Hypothetical transfers show that the differences observed between populations depend on the thermal conditions at the location of transfer, and that these differences are less marked in warmer conditions. 7 Our results indicate that local adaptation will probably not be a serious constraint in predicting the phenological responses of temperate lowland tree species to global warming

Consequences of low mate availability in the rare self-incompatible species Brassica insularis.

Self-incompatibility systems prevent self-fertilization in angiosperms. Although numerous S alleles are usually maintained by negative frequency-dependent selection, the number of S alleles can be low in small populations, which limits mate availability and reduces fecundity in endangered populations of self-incompatible plants. Despite the increasing evidence of the negative effect of self-incompatibility in small populations, the direct link between the number and the distribution of S alleles and their reproductive consequences has been rarely reported. Brassica insularis is a rare self-incompatible species with medium to very small populations. Results of a previous study showed that the smallest population has very few S alleles. We investigated whether reduced mate availability affects reproduction in this species. We compared the pollination success and the fruit set in 4 populations differing in population size and number of S alleles. Our results suggest that reproduction may be negatively affected by the low S-allele diversity in the smallest population. Nevertheless, other populations also had reduced fruit set that could not be attributed to self-incompatibility alone

Is Silene acaulis (Caryophyllaceae) a trioecious species? Reproductive biology of two subspecies

International audienceBased on morphological characters, Silene acaulis subsp. exscapa and Silene acaulis subsp. cenisia have been previously described as dioecious and trioecious, respectively. Here we examine whether these subspecies are truly dioecious (subsp. exscapa) and trioecious (subsp. cenisia) based on individual seed and pollen production. Nine populations of subsp. cenisia and five populations of subsp. exscapa were studied in the French Alps. The ratio of staminate to female plants within populations did not in general differ from 1:1, the sex ratio expected in dioecious populations. Staminate plants of both subspecies were found to set fruits. In subsp.exscapa, the ratio of fruit production in female versus staminate plants is around 900; in subsp. cenisia, this ratio is around 10. The advantage of female plants in fruit production is not always sufficient to explain their frequencies in natural populations. Staminate plants cannot be divided in two distinct categories: males and hermaphrodites. The two subspecies can be best described as subdioecious, although S. a. exscapa is effectively closer to exhibiting true dioecy than S. a. cenisia

Pollen aperture heteromorphism. Variation in pollen-type proportions along altitudinal transects in Viola calcarata

International audienceSome species produce pollen grains with different aperture numbers within a single individual (pollen aperture heteromorphism). In the pansy Viola diversifolia, aperture number is positively correlated with pollen germination speed, and negatively correlated with viability. In V calcarata, young five-aperturate pollen grains germinate faster than four-aperturate ones. Heteromorphism could thus be favoured when pollination is unpredictable, as plants produce both very competitive and long-lived pollen grains. Depending on the efficiency of the pollinators, different proportions of pollen types will be optimal. In insect-pollinated species, such as V:calcarata, pollination efficiency generally decreases as elevation increases. We therefore expect a decrease in mean aperture number as altitude increases. This was found in four transects tout of six). Pollinator activity therefore has a potential impact on pollen morphology. (C) Academie des Sciences/ Elsevier, Paris