A simple algorithm for quantifying DNA methylation levels on multiple independent CpG sites in bisulfite genomic sequencing electropherograms

DNA methylation at cytosines is a widely studied epigenetic modification. Methylation is commonly detected using bisulfite modification of DNA followed by PCR and additional techniques such as restriction digestion or sequencing. These additional techniques are either laborious, require specialized equipment, or are not quantitative. Here we describe a simple algorithm that yields quantitative results from analysis of conventional four-dye-trace sequencing. We call this method Mquant and we compare it with the established laboratory method of combined bisulfite restriction assay (COBRA). This analysis of sequencing electropherograms provides a simple, easily applied method to quantify DNA methylation at specific CpG sites

Genome-level homology and phylogeny of Shewanella (Gammaproteobacteria: lteromonadales: Shewanellaceae)

<p>Abstract</p> <p>Background</p> <p>The explosion in availability of whole genome data provides the opportunity to build phylogenetic hypotheses based on these data as well as the ability to learn more about the genomes themselves. The biological history of genes and genomes can be investigated based on the taxomonic history provided by the phylogeny. A phylogenetic hypothesis based on complete genome data is presented for the genus <it>Shewanella </it>(Gammaproteobacteria: Alteromonadales: Shewanellaceae). Nineteen taxa from <it>Shewanella </it>(16 species and 3 additional strains of one species) as well as three outgroup species representing the genera <it>Aeromonas </it>(Gammaproteobacteria: Aeromonadales: Aeromonadaceae), <it>Alteromonas </it>(Gammaproteobacteria: Alteromonadales: Alteromonadaceae) and <it>Colwellia </it>(Gammaproteobacteria: Alteromonadales: Colwelliaceae) are included for a total of 22 taxa.</p> <p>Results</p> <p>Putatively homologous regions were found across unannotated genomes and tested with a phylogenetic analysis. Two genome-wide data-sets are considered, one including only those genomic regions for which all taxa are represented, which included 3,361,015 aligned nucleotide base-pairs (bp) and a second that additionally includes those regions present in only subsets of taxa, which totaled 12,456,624 aligned bp. Alignment columns in these large data-sets were then randomly sampled to create smaller data-sets. After the phylogenetic hypothesis was generated, genome annotations were projected onto the DNA sequence alignment to compare the historical hypothesis generated by the phylogeny with the functional hypothesis posited by annotation.</p> <p>Conclusions</p> <p>Individual phylogenetic analyses of the 243 locally co-linear genome regions all failed to recover the genome topology, but the smaller data-sets that were random samplings of the large concatenated alignments all produced the genome topology. It is shown that there is not a single orthologous copy of 16S rRNA across the taxon sampling included in this study and that the relationships among the multiple copies are consistent with 16S rRNA undergoing concerted evolution. Unannotated whole genome data can provide excellent raw material for generating hypotheses of historical homology, which can be tested with phylogenetic analysis and compared with hypotheses of gene function.</p

Increased cardiovascular risk in rats with primary renal dysfunction; mediating role for vascular endothelial function

Primary chronic kidney disease is associated with high cardiovascular risk. However, the exact mechanisms behind this cardiorenal interaction remain unclear. We investigated the interaction between heart and kidneys in novel animal model for cardiorenal interaction. Normal Wistar rats and Munich Wistar Fromter rats, spontaneously developing renal dysfunction, were subjected to experimental myocardial infarction to induce cardiac dysfunction (CD) and combined cardiorenal dysfunction (CRD), respectively (N = 5–10). Twelve weeks later, cardiac- and renal parameters were evaluated. Cardiac, but not renal dysfunction was exaggerated in CRD. Accelerated cardiac dysfunction in CRD was indicated by decreased cardiac output (CD 109 ± 10 vs. CRD 79 ± 8 ml/min), diastolic dysfunction (E/e′) (CD 26 ± 2 vs. CRD 50 ± 5) and left ventricular overload (LVEDP CD 10.8 ± 2.8 vs. CRD 21.6 ± 1.7 mmHg). Congestion in CRD was confirmed by increased lung and atrial weights, as well as exaggerated right ventricular hypertrophy. Absence of accelerated renal dysfunction, measured by increased proteinuria, was supported by absence of additional focal glomerulosclerosis or further decline of renal blood flow in CRD. Only advanced peripheral endothelial dysfunction, as found in CRD, appeared to correlate with both renal and cardiac dysfunction parameters. Thus, proteinuric rats with myocardial infarction showed accelerated cardiac but not renal dysfunction. As parameters mimic the cardiorenal syndrome, these rats may provide a clinically relevant model to study increased cardiovascular risk due to renal dysfunction. Peripheral endothelial dysfunction was the only parameter that correlated with both renal and cardiac dysfunction, which may indicate a mediating role in cardiorenal interaction

Animal models of cardiorenal syndrome: a review

The incidence of heart failure and renal failure is increasing and is associated with poor prognosis. Moreover, these conditions do often coexist and this coexistence results in worsened outcome. Various mechanisms have been proposed as an explanation of this interrelation, including changes in hemodynamics, endothelial dysfunction, inflammation, activation of renin-angiotensin-aldosterone system, and/or sympathetic nervous system. However, the exact mechanisms initializing and maintaining this interaction are still unknown. In many experimental studies on cardiac or renal dysfunction, the function of the other organ was either not addressed or the authors failed to show any decline in its function despite histological changes. There are few studies in which the dysfunction of both heart and kidney function has been described. In this review, we discuss animal models of combined cardiorenal dysfunction. We show that translation of the results from animal studies is limited, and there is a need for new and better models of the cardiorenal interaction to improve our understanding of this syndrome. Finally, we propose several requirements that a new animal model should meet to serve as a tool for studies on the cardiorenal syndrome

Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer (vol 313, pg 1347, 2015)

Heli Nevanlinna ja Kristiina Aittomäki ovat CIMBA Consortium -työryhmän jäseniä.IMPORTANCE Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES Breast and ovarian cancer risks. RESULTS Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317(12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682(6%) with ovarian cancer, 272(2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% Cl, 1.22-1.74; P = 2 x 10(-6)), c.4328 to c.4945 (BCCR2; RH R = 1.34; 95% Cl, 1.01-1.78; P =.04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% Cl, 1.22-1.55; P = 6 x 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% Cl, 0.56-0.70; P = 9 x 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% Cl, 1.06-2.78; P =.03), c.772 to c.1806 (BCCRI; RHR = 1.63; 95% Cl, 1.10-2.40; P =.01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% Cl, 1.69-3.16; P =.00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% Cl, 0.44-0.60; P = 6 x 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% Cl, 0.41-0.80; P =.001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.Peer reviewe

Dense sampling of bird diversity increases power of comparative genomics (vol 587, pg 252, 2020)

Publishe

Fauna Europaea: Diptera -Brachycera

Link to publication Citation for published version (APA): Pape, T., Beuk, P., Pont, A. C., Shatalkin, A. I., Ozerov, A. L., Woźnica, A. J., ... de Jong, Y. (2015). Fauna Europaea: 3, [e4187]. https://doi.org/10.3897/BDJ.3.e4187 General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract Fauna Europaea provides a public web-service with an index of scientific names (including important synonyms) of all extant multicellular European terrestrial and freshwater animals and their geographical distribution at the level of countries and major islands (east of the Urals and excluding the Caucasus region). The Fauna Europaea project comprises about 230,000 taxonomic names, including 130,000 accepted species and 14,000 accepted subspecies, which is much more than the originally projected number of 100,000 species. Fauna Europaea represents a huge effort by more than 400 contributing taxonomic specialists throughout Europe and is a unique (standard) reference suitable for many user communities in science, government, industry, nature conservation and education. The Diptera-Brachycera is one of the 58 Fauna Europaea major taxonomic groups, and data have been compiled by a network of 55 specialists. Within the two-winged insects (Diptera), the Brachycera constitute a monophyletic group, which is generally given rank of suborder. The Brachycera may be classified into the probably paraphyletic &apos;lower brachyceran grade&apos; and the monophyletic Eremoneura. The latter contains the Empidoidea, the Apystomyioidea with a single Nearctic species, and the Cyclorrhapha, which in turn is divided into the paraphyletic &apos;aschizan grade&apos; and the monophyletic Schizophora. The latter is traditionally divided into the paraphyletic &apos;acalyptrate grade&apos; and the monophyletic Calyptratae. Our knowledge of the European fauna of Diptera-Brachycera varies tremendously among families, from the reasonably well known hoverflies (Syrphidae) to the extremely poorly known scuttle flies (Phoridae). There has been a steady growth in our knowledge of European Diptera for the last two centuries, with no apparent slow down, but there is a shift towards a larger fraction of the new species being found among the families of the nematoceran grade (lower Diptera), which due to a larger number of small-sized species may be considered as taxonomically more challenging. Most of Europe is highly industrialised and has a high human population density, and the more fertile habitats are extensively cultivated. This has undoubtedly increased the extinction risk for numerous species of brachyceran flies, yet with the recent re-discovery of Thyreophora cynophila (Panzer), there are no known cases of extinction at a European level. However, few national Red Lists have extensive information on Diptera. For the Diptera-Brachycera, data from 96 families containing 11,751 species are included in this paper

Changes to the Fossil Record of Insects through Fifteen Years of Discovery

The first and last occurrences of hexapod families in the fossil record are compiled from publications up to end-2009. The major features of these data are compared with those of previous datasets (1993 and 1994). About a third of families (>400) are new to the fossil record since 1994, over half of the earlier, existing families have experienced changes in their known stratigraphic range and only about ten percent have unchanged ranges. Despite these significant additions to knowledge, the broad pattern of described richness through time remains similar, with described richness increasing steadily through geological history and a shift in dominant taxa, from Palaeoptera and Polyneoptera to Paraneoptera and Holometabola, after the Palaeozoic. However, after detrending, described richness is not well correlated with the earlier datasets, indicating significant changes in shorter-term patterns. There is reduced Palaeozoic richness, peaking at a different time, and a less pronounced Permian decline. A pronounced Triassic peak and decline is shown, and the plateau from the mid Early Cretaceous to the end of the period remains, albeit at substantially higher richness compared to earlier datasets. Origination and extinction rates are broadly similar to before, with a broad decline in both through time but episodic peaks, including end-Permian turnover. Origination more consistently exceeds extinction compared to previous datasets and exceptions are mainly in the Palaeozoic. These changes suggest that some inferences about causal mechanisms in insect macroevolution are likely to differ as well