A genetic linkage map and comparative mapping of the prairie vole (Microtus ochrogaster) genome

<p>Abstract</p> <p>Background</p> <p>The prairie vole (<it>Microtus ochrogaster</it>) is an emerging rodent model for investigating the genetics, evolution and molecular mechanisms of social behavior. Though a karyotype for the prairie vole has been reported and low-resolution comparative cytogenetic analyses have been done in this species, other basic genetic resources for this species, such as a genetic linkage map, are lacking.</p> <p>Results</p> <p>Here we report the construction of a genome-wide linkage map of the prairie vole. The linkage map consists of 406 markers that are spaced on average every 7 Mb and span an estimated ~90% of the genome. The sex average length of the linkage map is 1707 cM, which, like other Muroid rodent linkage maps, is on the lower end of the length distribution of linkage maps reported to date for placental mammals. Linkage groups were assigned to 19 out of the 26 prairie vole autosomes as well as the X chromosome. Comparative analyses of the prairie vole linkage map based on the location of 387 Type I markers identified 61 large blocks of synteny with the mouse genome. In addition, the results of the comparative analyses revealed a potential elevated rate of inversions in the prairie vole lineage compared to the laboratory mouse and rat.</p> <p>Conclusions</p> <p>A genetic linkage map of the prairie vole has been constructed and represents the fourth genome-wide high-resolution linkage map reported for Muroid rodents and the first for a member of the Arvicolinae sub-family. This resource will advance studies designed to dissect the genetic basis of a variety of social behaviors and other traits in the prairie vole as well as our understanding of genome evolution in the genus <it>Microtus</it>.</p

The Amateur Sky Survey Mark III Project

The Amateur Sky Survey (TASS) is a loose confederation of amateur and professional astronomers. We describe the design and construction of our Mark III system, a set of wide-field drift-scan CCD cameras which monitor the celestial equator down to thirteenth magnitude in several passbands. We explain the methods by which images are gathered, processed, and reduced into lists of stellar positions and magnitudes. Over the period October, 1996, to November, 1998, we compiled a large database of photometric measurements. One of our results is the "tenxcat" catalog, which contains measurements on the standard Johnson-Cousins system for 367,241 stars; it contains links to the light curves of these stars as well.Comment: 20 pages, including 4 figures; additional JPEG files for Figures 1, 2. Submitted to PAS

Development of genomic resources for the prairie vole (Microtus ochrogaster): construction of a BAC library and vole-mouse comparative cytogenetic map

<p>Abstract</p> <p>Background</p> <p>The prairie vole (<it>Microtus ochrogaster</it>) is a premier animal model for understanding the genetic and neurological basis of social behaviors. Unlike other biomedical models, prairie voles display a rich repertoire of social behaviors including the formation of long-term pair bonds and biparental care. However, due to a lack of genomic resources for this species, studies have been limited to a handful of candidate genes. To provide a substrate for future development of genomic resources for this unique model organism, we report the construction and characterization of a bacterial artificial chromosome (BAC) library from a single male prairie vole and a prairie vole-mouse (<it>Mus musculus</it>) comparative cytogenetic map.</p> <p>Results</p> <p>We constructed a prairie vole BAC library (CHORI-232) consisting of 194,267 recombinant clones with an average insert size of 139 kb. Hybridization-based screening of the gridded library at 19 loci established that the library has an average depth of coverage of ~10×. To obtain a small-scale sampling of the prairie vole genome, we generated 3884 BAC end-sequences totaling ~2.8 Mb. One-third of these BAC-end sequences could be mapped to unique locations in the mouse genome, thereby anchoring 1003 prairie vole BAC clones to an orthologous position in the mouse genome. Fluorescence in situ hybridization (FISH) mapping of 62 prairie vole clones with BAC-end sequences mapping to orthologous positions in the mouse genome was used to develop a first-generation genome-wide prairie vole-mouse comparative cytogenetic map. While conserved synteny was observed between this pair of rodent genomes, rearrangements between the prairie vole and mouse genomes were detected, including a minimum of five inversions and 16 inter-chromosomal rearrangements.</p> <p>Conclusions</p> <p>The construction of the prairie vole BAC library and the vole-mouse comparative cytogenetic map represent the first genome-wide modern genomic resources developed for this species. The BAC library will support future genomic, genetic and molecular characterization of this genome and species, and the isolation of clones of high interest to the vole research community will allow for immediate characterization of the regulatory and coding sequences of genes known to play important roles in social behaviors. In addition, these resources provide an excellent platform for future higher resolution cytogenetic mapping and full genome sequencing.</p

BAC-Based Sequencing of Behaviorally-Relevant Genes in the Prairie Vole

The prairie vole (Microtus ochrogaster) is an important model organism for the study of social behavior, yet our ability to correlate genes and behavior in this species has been limited due to a lack of genetic and genomic resources. Here we report the BAC-based targeted sequencing of behaviorally-relevant genes and flanking regions in the prairie vole. A total of 6.4 Mb of non-redundant or haplotype-specific sequence assemblies were generated that span the partial or complete sequence of 21 behaviorally-relevant genes as well as an additional 55 flanking genes. Estimates of nucleotide diversity from 13 loci based on alignments of 1.7 Mb of haplotype-specific assemblies revealed an average pair-wise heterozygosity (8.4×10−3). Comparative analyses of the prairie vole proteins encoded by the behaviorally-relevant genes identified >100 substitutions specific to the prairie vole lineage. Finally, our sequencing data indicate that a duplication of the prairie vole AVPR1A locus likely originated from a recent segmental duplication spanning a minimum of 105 kb. In summary, the results of our study provide the genomic resources necessary for the molecular and genetic characterization of a high-priority set of candidate genes for regulating social behavior in the prairie vole

TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes

Abstract:P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to -2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome

Ejaculate Economics: Testing the Effects of Male Sexual History on the Trade-Off between Sperm and Immune Function in Australian Crickets

Trade-offs between investment into male sexual traits and immune function provide the foundation for some of the most prominent models of sexual selection. Post-copulatory sexual selection on the male ejaculate is intense, and therefore trade-offs should occur between investment into the ejaculate and the immune system. Examples of such trade-offs exist, including that between sperm quality and immunity in the Australian cricket, Teleogryllus oceanicus. Here, we explore the dynamics of this trade-off, examining the effects that increased levels of sexual interaction have on the viability of a male's sperm across time, and the concomitant effects on immune function. Males were assigned to a treatment, whereby they cohabited with females that were sexually immature, sexually mature but incapable of copulation, or sexually mature and capable of copulation. Sperm viability of each male was then assessed at two time points: six and 13 days into the treatment, and immune function at day 13. Sperm viability decreased across the time points, but only for males exposed to treatment classes involving sexually mature females. This decrease was similar in magnitude across both sexually mature classes, indicating that costs to the expression of high sperm viability are incurred largely through levels of pre-copulatory investment. Males exposed to immature females produced sperm of low viability at both time points. Although we confirmed a weak negative association between sperm viability and lytic activity (a measure of immune response to bacterial infection) at day 13, this relationship was not altered across the mating treatment. Our results highlight that sperm viability is a labile trait, costly to produce, and subject to strategic allocation in these crickets

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Divergence in transcriptional and regulatory responses to mating in male and female fruitflies

Mating induces extensive physiological, biochemical and behavioural changes in female animals of many taxa. In contrast, the overall phenotypic and transcriptomic consequences of mating for males, hence how they might differ from those of females, are poorly described. Post mating responses in each sex are rapidly initiated, predicting the existence of regulatory mechanisms in addition to transcriptional responses involving de novo gene expression. That post mating responses appear different for each sex also predicts that the genome-wide signatures of mating should show evidence of sex-specific specialisation. In this study, we used high resolution RNA sequencing to provide the first direct comparisons of the transcriptomic responses of male and female Drosophila to mating, and the first comparison of mating-responsive miRNAs in both sexes in any species. As predicted, the results revealed the existence of sex- and body part-specific mRNA and miRNA expression profiles. More genes were differentially expressed in the female head-thorax than the abdomen following mating, whereas the opposite was true in males. Indeed, the transcriptional profile of male head-thorax tissue was largely unaffected by mating, and no differentially expressed genes were detected at the most stringent significance threshold. A subset of ribosomal genes in females were differentially expressed in both body parts, but in opposite directions, consistent with the existence of body part-specific resource allocation switching. Novel, mating-responsive miRNAs in each sex were also identified, and a miRNA-mRNA interactions analysis revealed putative targets among mating-responsive genes. We show that the structure of genome-wide responses by each sex to mating is strongly divergent, and provide new insights into how shared genomes can achieve characteristic distinctiveness

Identification of Shell Colour Pigments in Marine Snails Clanculus pharaonius and C. margaritarius (Trochoidea; Gastropoda)

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ The attached file is the published version of the article

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts