Large-scale discovery of novel genetic causes of developmental disorders

Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders1, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach2 to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing3,4,5,6,7,8,9,10,11 and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders

Diversity of leaf katydids (Orthoptera: Tettigoniidae: Phaneropterinae) of Dzanga-Ndoki National Park, Central African Republic, with selected records from other African countries.

Forty-four species of Phaneropterinae are recorded from Dzanga-Ndoki National Park in the Central African Republic. Eight species collected within the park are described as new to science: Phlaurocentrum morettoi n. sp., P. paratuberosum n. sp., P. elegans n. sp., Myllocentrum raggei n. sp., Poreuomena sanghensis n. sp., Cestromoecha longicerca n. sp., C. magnicerca n. sp., and Goetia purpurea n. sp. An additional new species from Guinea is described from specimens preserved in the Museo Nacional de Ciencias Naturales of Madrid, Poreuomena huxleyi n. sp. Eurycorypha stylata St\ue5l, 1873 is recorded for the first time from Burkina Faso and Brycoptera lobata Ragge, 1981 from Ivory Coast. The following synonyms are established: Enochletica affinis Bol\uedvar, 1906 is synonymized with Enochletica ostentatrix Karsch, 1896, Poreuomena gladiator Bol\uedvar, 1906 is synonymized with Poreuomena forcipata Sj\uf6stedt, 1902, and Azamia doriae (Griffini, 1906) is synonymized with Azamia biplagiata Bol\uedvar, 1906. In addition, morphological characters of previously unknown females of Phaneroptera maculosa Ragge, 1956 and Eurycorypha canaliculata Karsch, 1890, and males of Myllocentrum stigmosum (Karsch, 1896) and Cestromoecha crassipes (Karsch, 1890) are described. The presence of titillators in four African genera (Gelotopoia, Brycoptera, Phlaurocentrum and Azamia) is recorded for the first time. In the genus Zeuneria, a sub-equally bilobed, dorsally curved, dorso-lateral abdominal appendage is described for the first time. This new structure apparently delimits an abdominal gland of unknown function on the second tergite

300 million years of diversification: elucidating the patterns of orthopteran evolution based on comprehensive taxon and gene sampling

Orthoptera is the most diverse order among the polyneopteran groups and includes familiar insects, such as grasshoppers, crickets, katydids, and their kin. Due to a long history of conflicting classification schemes based on different interpretations of morphological characters, the phylogenetic relationships within Orthoptera are poorly understood and its higher classification has remained unstable. In this study, we establish a robust phylogeny of Orthoptera including 36 of 40 families representing all 15 currently recognized superfamilies and based on complete mitochondrial genomes and four nuclear loci, in order to test previous phylogenetic hypotheses and to provide a framework for a natural classification and a reference for studying the pattern of divergence and diversification. We find strong support for monophyletic suborders (Ensifera and Caelifera) as well as major superfamilies. Our results corroborate most of the higher-level relationships previously proposed for Caelifera, but suggest some novel relationships for Ensifera. Using fossil calibrations, we provide divergence time estimates for major orthopteran lineages and show that the current diversity has been shaped by dynamic shifts of diversification rates at different geological times across different lineages. We also show that mitochondrial tRNA gene orders have been relatively stable throughout the evolutionary history of Orthoptera, but a major tRNA gene rearrangement occurred in the common ancestor of Tetrigoidea and Acridomorpha, thereby representing a robust molecular synapomorphy, which has persisted for 250 Myr.Fil: Song, Hojun. Texas A&M University; Estados Unidos. University of Central Florida; Estados UnidosFil: Amédégnato, Christiane. Museum National D; FranciaFil: Cigliano, Maria Marta. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Desutter Grandcolas, Laure. Museum National D; FranciaFil: Heads, Sam W.. University Of Illinois At Urbana; Estados UnidosFil: Huang, Yuan. Shaanxi Normal University; ChinaFil: Otte, Daniel. Drexel University; Estados UnidosFil: Whiting, Michael F.. University Brigham Young; Estados Unido