Association Weight Matrix for the Genetic Dissection of Puberty in Beef Cattle
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PARSANA-DISSERTATION-2020.Pdf
DECIPHERING TRANSCRIPTIONAL PATTERNS OF GENE REGULATION: A COMPUTATIONAL APPROACH by Princy Parsana A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July, 2020 © 2020 Princy Parsana All rights reserved Abstract With rapid advancements in sequencing technology, we now have the ability to sequence the entire human genome, and to quantify expression of tens of thousands of genes from hundreds of individuals. This provides an extraordinary opportunity to learn phenotype relevant genomic patterns that can improve our understanding of molecular and cellular processes underlying a trait. The high dimensional nature of genomic data presents a range of computational and statistical challenges. This dissertation presents a compilation of projects that were driven by the motivation to efficiently capture gene regulatory patterns in the human transcriptome, while addressing statistical and computational challenges that accompany this data. We attempt to address two major difficulties in this domain: a) artifacts and noise in transcriptomic data, andb) limited statistical power. First, we present our work on investigating the effect of artifactual variation in gene expression data and its impact on trans-eQTL discovery. Here we performed an in-depth analysis of diverse pre-recorded covariates and latent confounders to understand their contribution to heterogeneity in gene expression measurements. Next, we discovered 673 trans-eQTLs across 16 human tissues using v6 data from the Genotype Tissue Expression (GTEx) project. Finally, we characterized two trait-associated trans-eQTLs; one in Skeletal Muscle and another in Thyroid. Second, we present a principal component based residualization method to correct gene expression measurements prior to reconstruction of co-expression networks. -
Mouse Spock1 Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Spock1 Knockout Project (CRISPR/Cas9) Objective: To create a Spock1 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Spock1 gene (NCBI Reference Sequence: NM_009262 ; Ensembl: ENSMUSG00000056222 ) is located on Mouse chromosome 13. 12 exons are identified, with the ATG start codon in exon 2 and the TAG stop codon in exon 12 (Transcript: ENSMUST00000185502). Exon 5 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a targeted null mutation display no obvious morphological or behavioral abnormalities, are fertile, and have normal life spans. Adult homozygotes exhibit normal brain morphology and EEG recordings. Exon 5 starts from about 18.25% of the coding region. Exon 5 covers 8.67% of the coding region. The size of effective KO region: ~115 bp. The KO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 5 12 Legends Exon of mouse Spock1 Knockout region Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section upstream of Exon 5 is aligned with itself to determine if there are tandem repeats. Tandem repeats are found in the dot plot matrix. The gRNA site is selected outside of these tandem repeats. -
NBR1 (D2E6) Rabbit Mab A
Revision 1 C 0 2 - t NBR1 (D2E6) Rabbit mAb a e r o t S Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) 1 9 Web: [email protected] 8 www.cellsignal.com 9 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source/Isotype: UniProt ID: Entrez-Gene Id: WB, IP, IF-IC, F H M Endogenous 120 Rabbit IgG Q14596 4077 Product Usage Information Application Dilution Western Blotting 1:1000 Immunoprecipitation 1:50 Immunofluorescence (Immunocytochemistry) 1:1600 Flow Cytometry 1:50 Storage Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02% sodium azide. Store at –20°C. Do not aliquot the antibody. Specificity / Sensitivity NBR1 (D2E6) Rabbit mAb recognizes endogenous levels of total NBR1 protein. Species Reactivity: Human, Mouse Source / Purification Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Lys601 of human NBR1 protein. Background Next to BRCA1 gene 1 (NBR1) protein is known for its encoding gene proximity to the BRCA1 tumor suppressor gene (1,2). N-terminal Phox and Bem1p (PB1) domains of NBR1 mediate its interaction with muscle specific titin kinase (3,4) and scaffolding protein p62 (4). NBR1 plays a role in autophagy by facilitating the autophagosomal degradation of ubiquitinated proteins independently and also in concert with p62 (5,6). 1. Campbell, I.G. et al. (1994) Hum Mol Genet 3, 589-94. 2. -
Discovery of Candidate DNA Methylation Cancer Driver Genes
Published OnlineFirst May 10, 2021; DOI: 10.1158/2159-8290.CD-20-1334 RESEARCH ARTICLE Discovery of Candidate DNA Methylation Cancer Driver Genes Heng Pan1,2,3, Loïc Renaud4,5,6,7, Ronan Chaligne4,5,6, Johannes Bloehdorn8, Eugen Tausch8, Daniel Mertens9, Anna Maria Fink10, Kirsten Fischer10, Chao Zhang3,6, Doron Betel3,6, Andreas Gnirke11, Marcin Imielinski1,3,4,5,12, Jérôme Moreaux13,14,15,16, Michael Hallek10, Alexander Meissner11,17, Stephan Stilgenbauer8, Catherine J. Wu11,18, Olivier Elemento1,2,3,5, and Dan A. Landau3,4,5,6 Downloaded from cancerdiscovery.aacrjournals.org on September 28, 2021. © 2021 American Association for Cancer Research. Published OnlineFirst May 10, 2021; DOI: 10.1158/2159-8290.CD-20-1334 ABSTRACT Epigenetic alterations, such as promoter hypermethylation, may drive cancer through tumor suppressor gene inactivation. However, we have limited ability to differentiate driver DNA methylation (DNAme) changes from passenger events. We developed DNAme driver inference–MethSig–accounting for the varying stochastic hypermethylation rate across the genome and between samples. We applied MethSig to bisulfite sequencing data of chronic lymphocytic leukemia (CLL), multiple myeloma, ductal carcinoma in situ, glioblastoma, and to methylation array data across 18 tumor types in TCGA. MethSig resulted in well-calibrated quantile–quantile plots and reproducible inference of likely DNAme drivers with increased sensitivity/specificity compared with benchmarked methods. CRISPR/Cas9 knockout of selected candidate CLL DNAme drivers provided a fitness advantage with and without therapeutic intervention. Notably, DNAme driver risk score was closely associated with adverse outcome in independent CLL cohorts. Collectively, MethSig represents a novel inference framework for DNAme driver discovery to chart the role of aberrant DNAme in cancer. -
Downloaded from Refseq Database ( Duct Development (After E7.5), in Which Both Ducts Re
Roly et al. BMC Genomics (2020) 21:688 https://doi.org/10.1186/s12864-020-07106-8 RESEARCH ARTICLE Open Access Transcriptional landscape of the embryonic chicken Müllerian duct Zahida Yesmin Roly, Rasoul Godini, Martin A. Estermann, Andrew T. Major, Roger Pocock and Craig A. Smith* Abstract Background: Müllerian ducts are paired embryonic tubes that give rise to the female reproductive tract in vertebrates. Many disorders of female reproduction can be attributed to anomalies of Müllerian duct development. However, the molecular genetics of Müllerian duct formation is poorly understood and most disorders of duct development have unknown etiology. In this study, we describe for the first time the transcriptional landscape of the embryonic Müllerian duct, using the chicken embryo as a model system. RNA sequencing was conducted at 1 day intervals during duct formation to identify developmentally-regulated genes, validated by in situ hybridization. Results: This analysis detected hundreds of genes specifically up-regulated during duct morphogenesis. Gene ontology and pathway analysis revealed enrichment for developmental pathways associated with cell adhesion, cell migration and proliferation, ERK and WNT signaling, and, interestingly, axonal guidance. The latter included factors linked to neuronal cell migration or axonal outgrowth, such as Ephrin B2, netrin receptor, SLIT1 and class A semaphorins. A number of transcriptional modules were identified that centred around key hub genes specifying matrix-associated signaling factors; SPOCK1, HTRA3 and ADGRD1. Several novel regulators of the WNT and TFG-β signaling pathway were identified in Müllerian ducts, including APCDD1 and DKK1, BMP3 and TGFBI.A number of novel transcription factors were also identified, including OSR1, FOXE1, PRICKLE1, TSHZ3 and SMARCA2. -
TLR4 Signaling SASH1 Is a Scaffold Molecule in Endothelial
SASH1 Is a Scaffold Molecule in Endothelial TLR4 Signaling Shauna M. Dauphinee, Ashley Clayton, Angela Hussainkhel, Cindy Yang, Yoo-Jin Park, Megan E. Fuller, Josip Blonder, This information is current as Timothy D. Veenstra and Aly Karsan of September 27, 2021. J Immunol 2013; 191:892-901; Prepublished online 17 June 2013; doi: 10.4049/jimmunol.1200583 http://www.jimmunol.org/content/191/2/892 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2013/06/17/jimmunol.120058 Material 3.DC1 http://www.jimmunol.org/ References This article cites 46 articles, 14 of which you can access for free at: http://www.jimmunol.org/content/191/2/892.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 27, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology SASH1 Is a Scaffold Molecule in Endothelial TLR4 Signaling Shauna M. Dauphinee,*,† Ashley Clayton,*,† Angela Hussainkhel,*,‡ Cindy Yang,x Yoo-Jin Park,x Megan E. -
Transcriptomic Analysis of Monocytes from HIV-Positive Men On
Lorenz et al. Human Genomics (2019) 13:59 https://doi.org/10.1186/s40246-019-0247-x PRIMARY RESEARCH Open Access Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms David R. Lorenz, Vikas Misra and Dana Gabuzda* Abstract Background: Tobacco smoking induces immunomodulatory and pro-inflammatory effects associated with transcriptome changes in monocytes and other immune cell types. While smoking is prevalent in HIV-infected (HIV+) individuals, few studies have investigated its effects on gene expression in this population. Here, we report whole-transcriptome analyses of 125 peripheral blood monocyte samples from ART-treated HIV+ and uninfected (HIV−) men enrolled in the Multicenter AIDS Cohort Study (MACS) (n=25 HIV+ smokers, n = 60 HIV+ non-smokers, n = 40 HIV− non-smoking controls). Gene expression profiling was performed using Illumina HumanHT-12 Expression BeadChip microarrays. Differential expression analysis was performed with weighted linear regression models using the R limma package, followed by functional enrichment and Ingenuity Pathway analyses. Results: A total of 286 genes were differentially expressed in monocytes from HIV+ smokers compared with HIV− non-smokers; upregulated genes (n = 180) were enriched for immune and interferon response, chemical/stress response, mitochondria, and extracellular vesicle gene ontology (GO) terms. Expression of genes related to immune/interferon responses (AIM2, FCGR1A-B, IFI16, SP100), stress/chemical responses (APAF1, HSPD1, KLF4), and mitochondrial function (CISD1, MTHFD2, SQOR) was upregulated in HIV+ non-smokers and further increased in HIV+ smokers. Gene expression changes associated with smoking in previous studies of human monocytes were also observed (SASH1, STAB1, PID1, MMP25). -
Molecular and Cytogenetic Analysis of the Spreading of X Inactivation in a Girl with Microcephaly, Mild Dysmorphic Features and T(X;5)(Q22.1;Q31.1)
European Journal of Human Genetics (2008) 16, 897–905 & 2008 Nature Publishing Group All rights reserved 1018-4813/08 $30.00 www.nature.com/ejhg ARTICLE Molecular and cytogenetic analysis of the spreading of X inactivation in a girl with microcephaly, mild dysmorphic features and t(X;5)(q22.1;q31.1) Roberto Giorda*,1,7, M Clara Bonaglia2,7, Greta Milani1, Anna Baroncini3, Francesca Spada3, Silvana Beri1, Giorgia Menozzi4, Marianna Rusconi1 and Orsetta Zuffardi5,6 1Molecular Biology Laboratory, ‘E. Medea’ Scientific Institute, Bosisio Parini, Lecco, Italy; 2Cytogenetics Laboratory, ‘E. Medea’ Scientific Institute, Bosisio Parini, Lecco, Italy; 3UO Genetica Medica, AUSL Imola, Imola, Italy; 4Bioinformatic Laboratory, ‘E. Medea’ Scientific Institute, Bosisio Parini, Lecco, Italy; 5Biologia Generale e Genetica Medica, Universita` di Pavia, Pavia, Italy; 6IRCCS Policlinico San Matteo, Pavia, Italy X chromosome inactivation involves initiation, propagation, and maintenance of gene inactivation. Studies of replication pattern and timing in X;autosome translocations have suggested that X inactivation may spread to autosomal DNA. To examine this phenomenon at the molecular level, we have tested the transcriptional activity of a number of chromosome 5 loci in a female subject with microcephaly, mild dysmorphic features and 46,X,der(X)t(X;5)(q22.1;q31.1) karyotype. RT-PCR analysis of 20 transcribed sequences spanning 5q31.1-qter revealed that nine of them were not expressed in somatic cell hybrid clones carrying the translocated chromosome. However, eight genes were expressed and therefore escaped inactivation. This direct expression test demonstrates that spreading of inactivation from the X chromosome to the adjoining autosomal DNA was incomplete and ‘patchy’. -
S42003-020-01397-Z.Pdf
ARTICLE https://doi.org/10.1038/s42003-020-01397-z OPEN HACS1 signaling adaptor protein recognizes a motif in the paired immunoglobulin receptor B cytoplasmic domain Jamie J. Kwan1, Sladjana Slavkovic 2, Michael Piazza2, Dingyan Wang4, Thorsten Dieckmann3, ✉ 1234567890():,; Philip E. Johnson 2, Xiao-Yan Wen4 & Logan W. Donaldson 1 Hematopoietic adaptor containing SH3 and SAM domains-1 (HACS1) is a signaling protein with two juxtaposed protein–protein interaction domains and an intrinsically unstructured region that spans half the sequence. Here, we describe the interaction between the HACS1 SH3 domain and a sequence near the third immunoreceptor tyrosine-based inhibition motif (ITIM3) of the paired immunoglobulin receptor B (PIRB). From surface plasmon resonance binding assays using a mouse and human PIRB ITIM3 phosphopeptides as ligands, the HACS1 SH3 domain and SHP2 N-terminal SH2 domain demonstrated comparable affinities in the micromolar range. Since the PIRB ITIM3 sequence represents an atypical ligand for an SH3 domain, we determined the NMR structure of the HACS1 SH3 domain and performed a chemical shift mapping study. This study showed that the binding site on the HACS1 SH3 domain for PIRB shares many of the same amino acids found in a canonical binding cleft normally associated with polyproline ligands. Molecular modeling suggests that the respective binding sites in PIRB ITIM3 for the HACS1 SH3 domain and the SHP2 SH2 domain are too close to permit simultaneous binding. As a result, the HACS1-PIRB partnership has the potential to amalgamate signaling pathways that influence both immune and neuronal cell fate. 1 Department of Biology, York University, 4700 Keele Street, Toronto M3J 1P3 ON, Canada. -
Datasheet: MCA3240Z Product Details
Datasheet: MCA3240Z Description: MOUSE ANTI HUMAN NBR1:Preservative Free Specificity: NBR1 Format: Preservative Free Product Type: Monoclonal Antibody Clone: 6B11 Isotype: IgG1 Quantity: 0.1 mg Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 0.1 - 10 ug/ml Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Suggested working dilutions are given as a guide only. It is recommended that the user titrates the product for use in their own system using appropriate negative/positive controls. Target Species Human Product Form Purified IgG - liquid Preparation Purified IgG prepared by affinity chromatography on Protein A Buffer Solution Phosphate buffered saline Preservative None present Stabilisers Approx. Protein Ig concentration 0.5 mg/ml Concentrations Immunogen Recombinant protein corresponding to aa 2-97 of human NBR1 External Database Links UniProt: Q14596 Related reagents Entrez Gene: 4077 NBR1 Related reagents Synonyms 1A13B, KIAA0049, M17S2 Page 1 of 3 Fusion Partners Spleen cells from BALB/c mice were fused with cells from the Sp2/0 myeloma cell line. Specificity Mouse anti Human NBR1 antibody, clone 6B11 recognizes human Next to BRCA1 gene 1 protein, also known as NBR1, Cell migration-inducing gene 19 protein, Membrane component chromosome 17 surface marker 2, Neighbor of BRCA1 gene 1 protein or Protein 1A1-3B. -
A Genome-Wide Association Study Identifies Genetic Variants
www.nature.com/scientificreports OPEN A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Received: 16 May 2016 Accepted: 06 December 2016 Ability Published: 03 February 2017 Huan Chen1,2,*, Xiao-hong Gu3,*, Yuxi Zhou4,5,*, Zeng Ge4,5,*, Bin Wang4,5, Wai Ting Siok6, Guoqing Wang4,5, Michael Huen7, Yuyang Jiang8, Li-Hai Tan1,9 & Yimin Sun4,5,8,10 Mathematics ability is a complex cognitive trait with polygenic heritability. Genome-wide association study (GWAS) has been an effective approach to investigate genetic components underlying mathematic ability. Although previous studies reported several candidate genetic variants, none of them exceeded genome-wide significant threshold in general populations. Herein, we performed GWAS in Chinese elementary school students to identify potential genetic variants associated with mathematics ability. The discovery stage included 494 and 504 individuals from two independent cohorts respectively. The replication stage included another cohort of 599 individuals. In total, 28 of 81 candidate SNPs that met validation criteria were further replicated. Combined meta-analysis of three cohorts identified four SNPs (rs1012694, rs11743006, rs17778739 and rs17777541) ofSPOCK1 gene showing association with mathematics ability (minimum p value 5.67 × 10−10, maximum β −2.43). The SPOCK1 gene is located on chromosome 5q31.2 and encodes a highly conserved glycoprotein testican-1 which was associated with tumor progression and prognosis as well as neurogenesis. This is the first study to report genome-wide significant association of individual SNPs with mathematics ability in general populations. Our preliminary results further supported the role of SPOCK1 during neurodevelopment. The genetic complexities underlying mathematics ability might contribute to explain the basis of human cognition and intelligence at genetic level. -
NBR1 Sirna (H): Sc-94187
SANTA CRUZ BIOTECHNOLOGY, INC. NBR1 siRNA (h): sc-94187 BACKGROUND SUPPORT REAGENTS NBR1 (neighbor of BRCA1 gene 1), also known as M17S2, MIG19 or 1A13B, is For optimal siRNA transfection efficiency, Santa Cruz Biotechnology’s a 966 amino acid protein that is encoded by a gene neighboring the well-char- siRNA Transfection Reagent: sc-29528 (0.3 ml), siRNA Transfection Medium: acterized tumor suppressor BRCA1. Originally thought to be the ovarian cancer sc-36868 (20 ml) and siRNA Dilution Buffer: sc-29527 (1.5 ml) are recom- antigen CA125, NBR1 contains structural motifs, including a B-box/coiled coil mended. Control siRNAs or Fluorescein Conjugated Control siRNAs are domain, an OPR domain and a ZZ-type zinc finger, that are characteristic of available as 10 µM in 66 µl. Each contain a scrambled sequence that will several proteins involved in cell transformation. NBR1 interacts with SQSTM1 not lead to the specific degradation of any known cellular mRNA. Fluorescein (sequestosome 1 protein), Titin and MuRF2 (muscle-specific RING finger pro- Conjugated Control siRNAs include: sc-36869, sc-44239, sc-44240 and tein 2), suggesting a possible role in developmental pathways. Two isoforms, sc-44241. Control siRNAs include: sc-37007, sc-44230, sc-44231, sc-44232, designated NBR1A and NBR1B, are expressed due to alternative splicing sc-44233, sc-44234, sc-44235, sc-44236, sc-44237 and sc-44238. events. Expression of both isoforms is downregulated in malignant mammary tissues, indicating that NBR1 may be involved in tumor suppression. GENE EXPRESSION MONITORING NBR1 (4BR): sc-130380 is recommended as a control antibody for monitoring REFERENCES of NBR1 gene expression knockdown by Western Blotting (starting dilution 1.