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https://www.readbyqxmd.com/read/28098771/breast-cancer-brain-metastases-clonal-evolution-in-clinical-context
#1
REVIEW
Jodi M Saunus, Amy E McCart Reed, Zhun Leong Lim, Sunil R Lakhani
Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28096490/comprehensive-essentiality-analysis-of-the-mycobacterium-tuberculosis-genome-via-saturating-transposon-mutagenesis
#2
Michael A DeJesus, Elias R Gerrick, Weizhen Xu, Sae Woong Park, Jarukit E Long, Cara C Boutte, Eric J Rubin, Dirk Schnappinger, Sabine Ehrt, Sarah M Fortune, Christopher M Sassetti, Thomas R Ioerger
: For decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. To date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. As a result, the essentiality of many genomic features, particularly small ones, could not be reliably assessed...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096395/genomic-analysis-reveals-major-determinants-of-cis-regulatory-variation-in-capsella-grandiflora
#3
Kim A Steige, Benjamin Laenen, Johan Reimegård, Douglas G Scofield, Tanja Slotte
Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE)...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096303/down-regulation-of-epas1-transcription-and-genetic-adaptation-of-tibetans-to-high-altitude-hypoxia
#4
Yi Peng, Chaoying Cui, Yaoxi He, Ouzhuluobu, Hui Zhang, Deying Yang, Qu Zhang, Bianbazhuoma, Lixin Yang, Yibo He, Kun Xiang, Xiaoming Zhang, Sushil Bhandari, Peng Shi, Yangla, Dejiquzong, Baimakangzhuo, Duojizhuoma, Yongyue Pan, Cirenyangji, Baimayangji, Gonggalanzi, Caijuan Bai, Bianba, Basang, Ciwangsangbu, Shuhua Xu, Hua Chen, Shimin Liu, Tianyi Wu, Xuebin Qi, Bing Su
Tibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2α (HIF-2α) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice display blunted physiological responses to chronic hypoxia, mirroring the situation in Tibetans...
January 17, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28095895/genome-wide-snp-analysis-using-2b-rad-sequencing-identifies-the-candidate-genes-putatively-associated-with-resistance-to-ivermectin-in-haemonchus-contortus
#5
Xiaoping Luo, Xiaona Shi, Chunxiu Yuan, Min Ai, Cheng Ge, Min Hu, Xingang Feng, Xiaoye Yang
BACKGROUND: The excessive and uncontrolled use of anthelmintics, e.g. ivermectin (IVM) for the treatment of livestock parasites has led to widespread resistance in gastrointestinal nematodes, such as Haemonchus contortus. There is an urgent need for better management of drug-use in nematode control and development of novel anthelmintics. Discovery and identification of anthelmintic resistance-associate molecules/markers can provide a basis for rational anthelmintics-use and development of novel drugs...
January 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28093854/reduced-representation-genome-sequencing-reveals-patterns-of-genetic-diversity-and-selection-in-apple
#6
Baiquan Ma, Liao Liao, Qian Peng, Ting Fang, Hui Zhou, Schuyler S Korban, Yuepeng Han
Identifying DNA sequence variations is a fundamental step towards deciphering the genetic basis of traits of interest. Here, a total of 20 cultivated and 10 wild apples were genotyped using specific-locus amplified fragment sequencing, and 39,635 single nucleotide polymorphism with no missing genotypes and evenly distributed along the genome were selected to investigate patterns of genome-wide genetic variations between cultivated and wild apples. Overall, wild apples displayed higher levels of genetic diversity than cultivated apples...
January 17, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/28093083/genetic-analysis-of-teat-number-in-pigs-reveals-some-developmental-pathways-independent-of-vertebra-number-and-several-loci-which-only-affect-a-specific-side
#7
Gary A Rohrer, Dan J Nonneman
BACKGROUND: Number of functional teats is an important trait in commercial swine production. As litter size increases, the number of teats must also increase to supply nutrition to all piglets. Therefore, a genome-wide association analysis was conducted to identify genomic regions that affect this trait in a commercial swine population. Genotypic data from the Illumina Porcine SNP60v1 BeadChip were available for 2951 animals with total teat number (TTN) records. A subset of these animals (n = 1828) had number of teats on each side recorded...
January 4, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28093066/predictive-performance-of-genomic-selection-methods-for-carcass-traits-in-hanwoo-beef-cattle-impacts-of-the-genetic-architecture
#8
Hossein Mehrban, Deuk Hwan Lee, Mohammad Hossein Moradi, Chung IlCho, Masoumeh Naserkheil, Noelia Ibáñez-Escriche
BACKGROUND: Hanwoo beef is known for its marbled fat, tenderness, juiciness and characteristic flavor, as well as for its low cholesterol and high omega 3 fatty acid contents. As yet, there has been no comprehensive investigation to estimate genomic selection accuracy for carcass traits in Hanwoo cattle using dense markers. This study aimed at evaluating the accuracy of alternative statistical methods that differed in assumptions about the underlying genetic model for various carcass traits: backfat thickness (BT), carcass weight (CW), eye muscle area (EMA), and marbling score (MS)...
January 4, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28093063/whole-genome-sequence-based-genomic-prediction-in-laying-chickens-with-different-genomic-relationship-matrices-to-account-for-genetic-architecture
#9
Guiyan Ni, David Cavero, Anna Fangmann, Malena Erbe, Henner Simianer
BACKGROUND: With the availability of next-generation sequencing technologies, genomic prediction based on whole-genome sequencing (WGS) data is now feasible in animal breeding schemes and was expected to lead to higher predictive ability, since such data may contain all genomic variants including causal mutations. Our objective was to compare prediction ability with high-density (HD) array data and WGS data in a commercial brown layer line with genomic best linear unbiased prediction (GBLUP) models using various approaches to weight single nucleotide polymorphisms (SNPs)...
January 16, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28092973/elevated-ambulatory-systolic-diastolic-pressure-regression-index-is-genetically-determined-in-hypertensive-patients-with-coronary-heart-disease
#10
Marcin Wirtwein, Olle Melander, Marketa Sjőgren, Michal Hoffmann, Krzysztof Narkiewicz, Marcin Gruchala, Wojciech Sobiczewski
OBJECTIVES: Ambulatory systolic-diastolic pressure regression index (ASDPRI) as a composite marker of cardiovascular (CV) properties is related to CV complications. However, genetic determinants of ASDPRI are not known. The aim of this study is to report the relationship between certain single nucleotide polymorphisms (SNP) and ASDPRI in hypertensive patients with CAD confirmed by coronary angiography. METHODS: A total of 1345 hypertensive subjects with CAD were included...
January 16, 2017: Blood Pressure
https://www.readbyqxmd.com/read/28091955/genome-wide-exploration-of-silicon-si-transporter-genes-lsi1-and-lsi2-in-plants-insights-into-si-accumulation-status-capacity-of-plants
#11
Recep Vatansever, Ibrahim Ilker Ozyigit, Ertugrul Filiz, Nermin Gozukara
Silicon (Si) is a nonessential, beneficial micronutrient for plants. It increases the plant stress tolerance in relation to its accumulation capacity. In this work, root Si transporter genes were characterized in 17 different plants and inferred for their Si-accumulation status. A total of 62 Si transporter genes (31 Lsi1 and 31 Lsi2) were identified in studied plants. Lsi1s were 261-324 residues protein with a MIP family domain whereas Lsi2s were 472-547 residues with a citrate transporter family domain. Lsi1s possessed characteristic sequence features that can be employed as benchmark in prediction of Si-accumulation status/capacity of the plants...
January 13, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28090672/a-powerful-statistical-framework-for-generalization-testing-in-gwas-with-application-to-the-hchs-sol
#12
Tamar Sofer, Ruth Heller, Marina Bogomolov, Christy L Avery, Mariaelisa Graff, Kari E North, Alex P Reiner, Timothy A Thornton, Kenneth Rice, Yoav Benjamini, Cathy C Laurie, Kathleen F Kerr
In genome-wide association studies (GWAS), "generalization" is the replication of genotype-phenotype association in a population with different ancestry than the population in which it was first identified. Current practices for declaring generalizations rely on testing associations while controlling the family-wise error rate (FWER) in the discovery study, then separately controlling error measures in the follow-up study. This approach does not guarantee control over the FWER or false discovery rate (FDR) of the generalization null hypotheses...
January 15, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28088409/genome-wide-association-analysis-and-pathways-enrichment-for-lactation-persistency-in-canadian-holstein-cattle
#13
D N Do, N Bissonnette, P Lacasse, F Miglior, M Sargolzaei, X Zhao, E M Ibeagha-Awemu
Lactation persistency (LP), defined as the rate of declining milk yield after milk peak, is an economically important trait for dairy cattle. Improving LP is considered a good alternative method for increasing overall milk production because it does not cause the negative energy balance and other health issues that cows experience during peak milk production. However, little is known about the biology of LP. A genome-wide association study (GWAS) and pathway enrichment were used to explore the genetic mechanisms underlying LP...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088192/nucleotide-diversity-inflation-as-a-genome-wide-response-to-experimental-lifespan-extension-in-drosophila-melanogaster
#14
Pawel Michalak, Lin Kang, Pernille M Sarup, Mads F Schou, Volker Loeschcke
BACKGROUND: Evolutionary theory predicts that antagonistically selected alleles, such as those with divergent pleiotropic effects in early and late life, may often reach intermediate population frequencies due to balancing selection, an elusive process when sought out empirically. Alternatively, genetic diversity may increase as a result of positive frequency-dependent selection and genetic purging in bottlenecked populations. RESULTS: While experimental evolution systems with directional phenotypic selection typically result in at least local heterozygosity loss, we report that selection for increased lifespan in Drosophila melanogaster leads to an extensive genome-wide increase of nucleotide diversity in the selected lines compared to replicate control lines, pronounced in regions with no or low recombination, such as chromosome 4 and centromere neighborhoods...
January 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28088170/application-of-a-bayesian-dominance-model-improves-power-in-quantitative-trait-genome-wide-association-analysis
#15
Jörn Bennewitz, Christian Edel, Ruedi Fries, Theo H E Meuwissen, Robin Wellmann
BACKGROUND: Multi-marker methods, which fit all markers simultaneously, were originally tailored for genomic selection purposes, but have proven to be useful also in association analyses, especially the so-called BayesC Bayesian methods. In a recent study, BayesD extended BayesC towards accounting for dominance effects and improved prediction accuracy and persistence in genomic selection. The current study investigated the power and precision of BayesC and BayesD in genome-wide association studies by means of stochastic simulations and applied these methods to a dairy cattle dataset...
January 14, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28088165/genomic-characterization-of-ensifer-aridi-a-proposed-new-species-of-nitrogen-fixing-rhizobium-recovered-from-asian-african-and-american-deserts
#16
Antoine Le Quéré, Nisha Tak, Hukam Singh Gehlot, Celine Lavire, Thibault Meyer, David Chapulliot, Sonam Rathi, Ilham Sakrouhi, Guadalupe Rocha, Marine Rohmer, Dany Severac, Abdelkarim Filali-Maltouf, Jose-Antonio Munive
BACKGROUND: Nitrogen fixing bacteria isolated from hot arid areas in Asia, Africa and America but from diverse leguminous plants have been recently identified as belonging to a possible new species of Ensifer (Sinorhizobium). In this study, 6 strains belonging to this new clade were compared with Ensifer species at the genome-wide level. Their capacities to utilize various carbon sources and to establish a symbiotic interaction with several leguminous plants were examined. RESULTS: Draft genomes of selected strains isolated from Morocco (Merzouga desert), Mexico (Baja California) as well as from India (Thar desert) were produced...
January 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28087779/genomics-of-parallel-experimental-evolution-in-drosophila
#17
J L Graves, K L Hertweck, M A Phillips, M V Han, L G Cabral, T T Barter, L F Greer, M K Burke, L D Mueller, M R Rose
What are the genomic foundations of adaptation in sexual populations? We address this question using fitness-character and whole-genome sequence data from 30 Drosophila laboratory populations. These 30 populations are part of a nearly forty-year laboratory radiation featuring three selection regimes, each shared by ten populations for up to 837 generations, with moderately large effective population sizes. Each of three sets of ten populations that shared a selection regime consist of five populations that have long been maintained under that selection regime, paired with five populations that had only recently been subjected to that selection regime...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087713/functional-genomics-reveals-that-tumors-with-activating-phosphoinositide-3-kinase-mutations-are-dependent-on-accelerated-protein-turnover
#18
Teresa Davoli, Kristen E Mengwasser, Jingjing Duan, Ting Chen, Camilla Christensen, Eric C Wooten, Anthony N Anselmo, Mamie Z Li, Kwok-Kin Wong, Kristopher T Kahle, Stephen J Elledge
Activating mutations in the phosphoinositide 3-kinase (PI3K) signaling pathway are frequently identified in cancer. To identify pathways that support PI3K oncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes. A combined analysis of these results with a meta-analysis of two other large-scale RNAi screening data sets in PI3K mutant cancer cell lines converged on ribosomal protein translation and proteasomal protein degradation as critical nononcogene dependencies for PI3K-driven tumors...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087289/clinical-utility-and-functional-analysis-of-variants-in-atrial-fibrillation-associated-locus-4q25
#19
Yusuke Ebana, Kouichi Ozaki, Lian Liu, Hitoshi Hachiya, Kenzo Hirao, Mitsuaki Isobe, Michiaki Kubo, Toshihiro Tanaka, Tetsushi Furukawa
BACKGROUND: Chromosome 4q25 has been repeatedly identified as atrial fibrillation (AF)-sensitive locus in multiple genome-wide association studies (GWAS) and is considered to hold some clues to AF pathogenesis. We aimed to investigate the clinical utilities in Japanese and to unveil the function of the 4q25 locus in affecting transcription of adjacent genes. METHODS: We conducted AF GWAS in Japanese population (1382 AF cases and 1478 controls) and the replication panel (1666 AF cases and 1229 controls) with detailed clinical information which showed the acceleration of AF onset...
January 10, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/28086750/a-genome-wide-scan-for-genes-under-balancing-selection-in-drosophila-melanogaster
#20
Myriam Croze, Andreas Wollstein, Vedran Božičević, Daniel Živković, Wolfgang Stephan, Stephan Hutter
BACKGROUND: In the history of population genetics balancing selection has been considered as an important evolutionary force, yet until today little is known about its abundance and its effect on patterns of genetic diversity. Several well-known examples of balancing selection have been reported from humans, mice, plants, and parasites. However, only very few systematic studies have been carried out to detect genes under balancing selection. We performed a genome scan in Drosophila melanogaster to find signatures of balancing selection in a derived (European) and an ancestral (African) population...
January 13, 2017: BMC Evolutionary Biology
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