De Novo Unbalanced Translocations in Prader-Willi and Angelman Syndrome Might Be the Reciprocal Product of inv dup(15)s

The 15q11-q13 region is characterized by high instability, caused by the presence of several paralogous segmental duplications. Although most mechanisms dealing with cryptic deletions and amplifications have been at least partly characterized, little is known about the rare translocations involving this region. We characterized at the molecular level five unbalanced translocations, including a jumping one, having most of 15q transposed to the end of another chromosome, whereas the der(15)(pter->q11-q13) was missing. Imbalances were associated either with Prader-Willi or Angelman syndrome. Array-CGH demonstrated the absence of any copy number changes in the recipient chromosome in three cases, while one carried a cryptic terminal deletion and another a large terminal deletion, already diagnosed by classical cytogenetics. We cloned the breakpoint junctions in two cases, whereas cloning was impaired by complex regional genomic architecture and mosaicism in the others. Our results strongly indicate that some of our translocations originated through a prezygotic/postzygotic two-hit mechanism starting with the formation of an acentric 15qter->q1::q1->qter representing the reciprocal product of the inv dup(15) supernumerary marker chromosome. An embryo with such an acentric chromosome plus a normal chromosome 15 inherited from the other parent could survive only if partial trisomy 15 rescue would occur through elimination of part of the acentric chromosome, stabilization of the remaining portion with telomere capture, and formation of a derivative chromosome. All these events likely do not happen concurrently in a single cell but are rather the result of successive stabilization attempts occurring in different cells of which only the fittest will finally survive. Accordingly, jumping translocations might represent successful rescue attempts in different cells rather than transfer of the same 15q portion to different chromosomes. We also hypothesize that neocentromerization of the original acentric chromosome during early embryogenesis may be required to avoid its loss before cell survival is finally assured

Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly

Type I lissencephaly or agyria-pachygyria is a rare developmental disorder which results from a defect of neuronal migration. It is characterized by the absence of gyri and a thickening of the cerebral cortex and can be associated with other brain and visceral anomalies. Since the discovery of the first genetic cause (deletion of chromosome 17p13.3), six additional genes have been found to be responsible for agyria–pachygyria. In this review, we summarize the current knowledge concerning these genetic disorders including clinical, neuropathological and molecular results. Genetic alterations of LIS1, DCX, ARX, TUBA1A, VLDLR, RELN and more recently WDR62 genes cause migrational abnormalities along with more complex and subtle anomalies affecting cell proliferation and differentiation, i.e., neurite outgrowth, axonal pathfinding, axonal transport, connectivity and even myelination. The number and heterogeneity of clinical, neuropathological and radiological defects suggest that type I lissencephaly now includes several forms of cerebral malformations. In vitro experiments and mutant animal studies, along with neuropathological abnormalities in humans are of invaluable interest for the understanding of pathophysiological mechanisms, highlighting the central role of cytoskeletal dynamics required for a proper achievement of cell proliferation, neuronal migration and differentiation

A high-resolution three-dimensional reconstruction of a fossil forest (Upper Jurassic Shishugou Formation, Junggar Basin, Northwest China)

This study focuses on the three-dimensional (3D) reconstruction of an Late Jurassic fossil forest based on a fossil assemblage located in the Shishugou Formation near Jiangjunmiao, north-eastern Junggar Basin, Xinjiang Uygur Autonomous Region, Northwest China. On the basis of tree stumps found in growth position together with published data on megaplant fossils, seeds and spores, a highresolution digital computer model, including different forest layers, was developed. In a study area of 31,500 m, 65 tree stumps with diameters between 0.2 and 2.9 m were mapped and subsequently used for the 3D reconstruction. The forest grew under moist conditions, probably close to the banks of an anastomosing river and consisted primarily of conifers, in particular Araucariaceae. Even though the tree density of the forest is only 22 trees/ha, the 3D reconstruction indicates a relatively closed canopy. Megaplant fossils and spores also show evidence for the presence of Angiopteris, Osmunda and Coniopteris, which were then used to reconstruct the understory of the forest. The trees were modelled in three different growth stages, representing young, older and mature trees, respectively. The growth parameters of individual trees and ferns were randomized in order to avoid duplications within the reconstruction. Detailed textures of leaves, fronds and bark were created to give the plants a more realistic appearance than that in previously published 3D reconstructions of fossil forest assemblages. Estimations of net biomass (approximately 9 tons/ha), annual biomass production and a calculation of nearest neighbour index (0.86) suggest an open forest with spatially distributed trees

New horizons for molecular genetics diagnostic and research in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable, heterogeneous, and complex pervasive neurodevelopmental disorder (PND) characterized by distinctive abnormalities of human cognitive functions, social interaction, and speech development.Nowadays, several genetic changes including chromosome abnormalities, genetic variations, transcriptional epigenetics, and noncoding RNA have been identified in ASD. However, the association between these genetic modifications and ASDs has not been confirmed yet.The aim of this review is to summarize the key findings in ASD from genetic viewpoint that have been identified from the last few decades of genetic and molecular research