Systematics And Origin Of Moths In The Subfamily Arctiinae (lepidoptera, Erebidae) In The Neotropical Region

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The availability of standard protocols to obtain DNA sequences has allowed the inference of phylogenetic Hypotheses for many taxa, including moths. We here have inferred a phylogeny using maximum-Likelihood and Bayesian approaches for a species-rich group of moths (Erebidae, Arctiinae), with strong emphasis on Neotropical genera collected in different field campaigns in the Atlantic Forest of Brazil, eastern Amazon and southern Ecuador. A total of 277 species belonging to 246 genera were included in the analysis. Our main objectives were to shed light on the relationships between suprageneric groups, especially subtribes, and hypothesize colonization events in and out of the Neotropics. The monophyly of Arctiinae and its four tribes (Lithosiini, Amerilini, Syntomini and Arctiini) was recovered in the ML and Bayesian trees. Three Lithosiini subtribes previously found and two additional species groups were recovered monophyletic in both phylogenetic estimation methods. In Arctiini, the monophyly of Spilosomina and Arctiina was highly supported in the ML and Bayesian trees, but the monophyly of Ctenuchina and Echromiina was weakly supported in the ML tree and absent in the Bayesian tree; the remaining subtribes were paraphyletic and, in the case of Phageopterina, formed several species groups. The mapping of species occurrence in our ML tree suggests that Arctiinae have an Old World origin and that the Neotropical region was colonized at least six times independently. Our analysis also suggests that a number of species that occur in Neotropical and other zoogeographic regions may have originated in the Neotropics, although further taxon sampling is required to support this hypothesis. To our knowledge, this is the first time that a highly speciose group of tropical moths is well covered in a phylogeny, and it seems plausible that the results reported here may be extendable to other species-rich tropical undersampled moth taxa. © 2016 Royal Swedish Academy of Sciences4633483622013/09647-7, FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo2014/06646-2, FAPESP, Fundação de Amparo à Pesquisa do Estado de São PauloDEB-1256742, NSF, National Science FoundationFi 547 10-2, DFG, Deutsche ForschungsgemeinschaftSuomen AkatemiaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Molecular karyotyping in patients with mental retardation using 100K single-nucleotide polymorphism arrays

BACKGROUND: Using different array techniques it was recently shown that about 10% of patients with mental retardation of unknown origin harbour cryptic chromosomal aneusomies. Nevertheless, data analysis is currently not standardized and little is known about its sensitivity and specificity. METHODS: We developed an electronic data analysis tool for GeneChip Mapping SNP arrays, which we called copy number variation finder (CNVF). Using the CNVF we analysed 104 unselected patients with mental retardation of unknown origin with the GeneChip Mapping 100K SNP array and established an optimized set of analysis parameters. RESULTS: We detected deletions as small as 20 kb when covered by at least 3 SNPs and duplications as small as 150 kb when covered by at least 6 SNPs with only one false positive signal per 6 patients. In 9.1% of patients we detected apparently disease-causing or de novo aberrations sizing 0.4-14 Mb. Morphological anomalies in patients with de novo aberrations were equal to that of unselected patients when measured with de Vries score. CONCLUSION: Our standardized data analysis tool CNVF is easy to use and has a high sensitivity and specificity. As some genomic regions are covered more densely than others the actual genome wide resolution of the 100 K array is about 400-500 kb for deletions and 900-1000 kb for duplications. Detection rate of about 10% de novo aberrations is independent from selection of patients for certain features. The incidental finding of heterozygosity for the 250 kb recurrent deletion at the NPH1 locus associated with autosomal recessive juvenile nephronophthisis in two patients being inherited from a healthy parent highlights the fact that inherited aberrations might be disease-related although not causal for mental retardation

Identification of genetic loci associated with <em>Helicobacter pylori</em> serologic status.

Importance Helicobacter pylori is a major cause of gastritis and gastroduodenal ulcer disease and can cause cancer. H pylori prevalence is as high as 90% in some developing countries but 10% of a given population is never colonized, regardless of exposure. Genetic factors are hypothesized to confer H pylori susceptibility. Objective To identify genetic loci associated with H pylori seroprevalence in 2 independent population-based cohorts and to determine their putative pathophysiological role by whole-blood RNA gene expression profiling. Design, Setting, and Participants Two independent genome-wide association studies (GWASs) and a subsequent meta-analysis were conducted for anti-H pylori IgG serology in the Study of Health in Pomerania (SHIP) (recruitment, 1997-2001 [n=3830]) as well as the Rotterdam Study (RS-I) (recruitment, 1990-1993) and RS-II (recruitment, 2000-2001 [n=7108]) populations. Whole-blood RNA gene expression profiles were analyzed in RS-III (recruitment, 2006-2008 [n=762]) and SHIP-TREND (recruitment, 2008-2012 [n=991]), and fecal H pylori antigen in SHIP-TREND (n=961). Main Outcomes and Measures H pylori seroprevalence. Results Of 10 938 participants, 6160 (56.3%) were seropositive for H pylori. GWASs identified the toll-like receptor (TLR) locus (4p14; top-ranked single-nucleotide polymorphism (SNP), rs10004195; P=1.4 x 10(-18); odds ratio, 0.70 [95% CI, 0.65 to 0.76]) and the FCGR2A locus (1q23.3; top-ranked SNP, rs368433; P=2.1 x 10(-8); odds ratio, 0.73 [95% CI, 0.65 to 0.81]) as associated with H pylori seroprevalence. Among the 3 TLR genes at 4p14, only TLR1 was differentially expressed per copy number of the minor rs10004195-A allele (beta =-0.23 [95% CI, -0.34 to -0.11]; P=2.1 x 10(-4)). Individuals with high fecal H pylori antigen titers (optical density &gt;1) also exhibited the highest 25% of TLR1 expression levels (P=.01 by chi(2) test). Furthermore, TLR1 exhibited an Asn248Ser substitution in the extracellular domain strongly linked to the rs10004195 SNP. Conclusions and Relevance GWAS meta-analysis identified an association between TLR1 and H pylori seroprevalence, a finding that requires replication in non-white populations. If confirmed, genetic variations in TLR1 may help explain some of the observed variation in individual risk for H pylori infection

Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder within the RASopathy Clinical Spectrum

Signal transduction through the RAF-MEK-ERK pathway, the first described mitogen-associated protein kinase (MAPK) cascade, mediates multiple cellular processes and participates in early and late developmental programs. Aberrant signaling through this cascade contributes to oncogenesis and underlies the RASopathies, a family of cancer-prone disorders. Here, we report that de novo missense variants in MAPK1, encoding the mitogen-activated protein kinase 1 (i.e., extracellular signal-regulated protein kinase 2, ERK2), cause a neurodevelopmental disease within the RASopathy phenotypic spectrum, reminiscent of Noonan syndrome in some subjects. Pathogenic variants promote increased phosphorylation of the kinase, which enhances translocation to the nucleus and boosts MAPK signaling in vitro and in vivo. Two variant classes are identified, one of which directly disrupts binding to MKP3, a dual-specificity protein phosphatase negatively regulating ERK function. Importantly, signal dysregulation driven by pathogenic MAPK1 variants is stimulus reliant and retains dependence on MEK activity. Our data support a model in which the identified pathogenic variants operate with counteracting effects on MAPK1 function by differentially impacting the ability of the kinase to interact with regulators and substrates, which likely explains the minor role of these variants as driver events contributing to oncogenesis. After nearly 20 years from the discovery of the first gene implicated in Noonan syndrome, PTPN11, the last tier of the MAPK cascade joins the group of genes mutated in RASopathies