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  • 1
    Publication Date: 1999-12-03
    Description: Osteoporosis and other diseases of bone loss are a major public health problem. Here it is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents. This effect was associated with increased expression of the bone morphogenetic protein-2 (BMP-2) gene in bone cells. Lovastatin and simvastatin increased bone formation when injected subcutaneously over the calvaria of mice and increased cancellous bone volume when orally administered to rats. Thus, in appropriate doses, statins may have therapeutic applications for the treatment of osteoporosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mundy, G -- Garrett, R -- Harris, S -- Chan, J -- Chen, D -- Rossini, G -- Boyce, B -- Zhao, M -- Gutierrez, G -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1946-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉OsteoScreen, 2040 Babcock Road, San Antonio, TX 78229, USA. mundy@uthscsa.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10583956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Density/*drug effects ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins/biosynthesis/genetics/pharmacology ; Cell Line ; Female ; Fibroblast Growth Factor 1 ; Fibroblast Growth Factor 2/pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Lovastatin/*pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Organ Culture Techniques ; Osteoblasts/*drug effects/metabolism ; Osteoclasts/drug effects ; Osteogenesis/*drug effects ; Osteoporosis/drug therapy ; Ovariectomy ; Promoter Regions, Genetic/drug effects ; Rats ; Recombinant Proteins/pharmacology ; Simvastatin/*pharmacology ; Skull ; Transfection ; *Transforming Growth Factor beta
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2001-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwartlander, B -- Stover, J -- Walker, N -- Bollinger, L -- Gutierrez, J P -- McGreevey, W -- Opuni, M -- Forsythe, S -- Kumaranayake, L -- Watts, C -- Bertozzi, S -- New York, N.Y. -- Science. 2001 Jun 29;292(5526):2434-6. Epub 2001 Jun 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joint United Nations Programme on HIV/AIDS (UNAIDS), Geneva, Switzerland. schwartlanderb@unaids.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11423619" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*economics/epidemiology/prevention & ; control/therapy ; Africa South of the Sahara ; Antiretroviral Therapy, Highly Active ; Developed Countries/economics ; Developing Countries/economics ; Female ; Financing, Organized ; *Global Health ; HIV Infections/*economics/epidemiology/prevention & control/therapy ; Health Care Costs ; *Health Expenditures ; *Health Resources ; Health Services/economics ; Humans ; International Cooperation ; Male ; Private Sector ; Public Sector ; United Nations
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2008-06-20
    Description: Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approximately 520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Putnam, Nicholas H -- Butts, Thomas -- Ferrier, David E K -- Furlong, Rebecca F -- Hellsten, Uffe -- Kawashima, Takeshi -- Robinson-Rechavi, Marc -- Shoguchi, Eiichi -- Terry, Astrid -- Yu, Jr-Kai -- Benito-Gutierrez, E Lia -- Dubchak, Inna -- Garcia-Fernandez, Jordi -- Gibson-Brown, Jeremy J -- Grigoriev, Igor V -- Horton, Amy C -- de Jong, Pieter J -- Jurka, Jerzy -- Kapitonov, Vladimir V -- Kohara, Yuji -- Kuroki, Yoko -- Lindquist, Erika -- Lucas, Susan -- Osoegawa, Kazutoyo -- Pennacchio, Len A -- Salamov, Asaf A -- Satou, Yutaka -- Sauka-Spengler, Tatjana -- Schmutz, Jeremy -- Shin-I, Tadasu -- Toyoda, Atsushi -- Bronner-Fraser, Marianne -- Fujiyama, Asao -- Holland, Linda Z -- Holland, Peter W H -- Satoh, Nori -- Rokhsar, Daniel S -- BBS/B/12067/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/B/12067/2/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Jun 19;453(7198):1064-71. doi: 10.1038/nature06967.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563158" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chordata/classification/*genetics ; Conserved Sequence ; DNA Transposable Elements/genetics ; *Evolution, Molecular ; Gene Duplication ; Genes/genetics ; Genetic Linkage ; Genome/*genetics ; Humans ; Introns/genetics ; Karyotyping ; Multigene Family ; Phylogeny ; Polymorphism, Genetic/genetics ; Proteins/genetics ; Synteny ; Time Factors ; Vertebrates/classification/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2009-08-01
    Description: Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type-specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type-specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type-specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867218/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867218/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dimas, Antigone S -- Deutsch, Samuel -- Stranger, Barbara E -- Montgomery, Stephen B -- Borel, Christelle -- Attar-Cohen, Homa -- Ingle, Catherine -- Beazley, Claude -- Gutierrez Arcelus, Maria -- Sekowska, Magdalena -- Gagnebin, Marilyne -- Nisbett, James -- Deloukas, Panos -- Dermitzakis, Emmanouil T -- Antonarakis, Stylianos E -- 077011/Wellcome Trust/United Kingdom -- 077046/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1246-50. doi: 10.1126/science.1174148. Epub 2009 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1HH, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644074" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; B-Lymphocytes ; Cell Line ; Enhancer Elements, Genetic ; Fibroblasts ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Frequency ; Genotype ; Humans ; *Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; RNA, Messenger/genetics/metabolism ; *Regulatory Elements, Transcriptional ; Statistics, Nonparametric ; T-Lymphocytes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2013-10-19
    Description: DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kilpinen, Helena -- Waszak, Sebastian M -- Gschwind, Andreas R -- Raghav, Sunil K -- Witwicki, Robert M -- Orioli, Andrea -- Migliavacca, Eugenia -- Wiederkehr, Michael -- Gutierrez-Arcelus, Maria -- Panousis, Nikolaos I -- Yurovsky, Alisa -- Lappalainen, Tuuli -- Romano-Palumbo, Luciana -- Planchon, Alexandra -- Bielser, Deborah -- Bryois, Julien -- Padioleau, Ismael -- Udin, Gilles -- Thurnheer, Sarah -- Hacker, David -- Core, Leighton J -- Lis, John T -- Hernandez, Nouria -- Reymond, Alexandre -- Deplancke, Bart -- Dermitzakis, Emmanouil T -- GM25232/GM/NIGMS NIH HHS/ -- HG004845/HG/NHGRI NIH HHS/ -- R01 HG004845/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):744-7. doi: 10.1126/science.1242463. Epub 2013 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136355" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Base Sequence/genetics ; Binding Sites/genetics ; Chromatin/chemistry/*metabolism ; DNA/chemistry/*metabolism ; *Gene Expression Regulation ; *Genetic Variation ; Histones/chemistry/metabolism ; Humans ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Transcription Factors/*metabolism ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2002-11-16
    Description: Recently, we showed that antibodies catalyze the generation of hydrogen peroxide (H2O2) from singlet molecular oxygen (1O2*) and water. Here, we show that this process can lead to efficient killing of bacteria, regardless of the antigen specificity of the antibody. H2O2 production by antibodies alone was found to be not sufficient for bacterial killing. Our studies suggested that the antibody-catalyzed water-oxidation pathway produced an additional molecular species with a chemical signature similar to that of ozone. This species is also generated during the oxidative burst of activated human neutrophils and during inflammation. These observations suggest that alternative pathways may exist for biological killing of bacteria that are mediated by potent oxidants previously unknown to biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wentworth, Paul Jr -- McDunn, Jonathan E -- Wentworth, Anita D -- Takeuchi, Cindy -- Nieva, Jorge -- Jones, Teresa -- Bautista, Cristina -- Ruedi, Julie M -- Gutierrez, Abel -- Janda, Kim D -- Babior, Bernard M -- Eschenmoser, Albert -- Lerner, Richard A -- 5T32AI07606/AI/NIAID NIH HHS/ -- GM43858/GM/NIGMS NIH HHS/ -- P01CA27489/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2195-9. Epub 2002 Nov 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12434011" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Catalytic/immunology/*metabolism ; Arthus Reaction/*immunology/metabolism ; Blood Bactericidal Activity ; Catalase/metabolism ; Catalysis ; Escherichia coli/*immunology ; Hematoporphyrins/metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Indigo Carmine/metabolism ; Inflammation/*immunology/metabolism ; Mice ; Neutrophil Activation ; Neutrophils/immunology/*metabolism ; Oxidation-Reduction ; Ozone/*metabolism ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Respiratory Burst ; Singlet Oxygen/metabolism ; Ultraviolet Rays ; Water/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2011-03-04
    Description: The effective use of targeted therapy is highly dependent on the identification of responder patient populations. Loss of FBW7, which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast cancer, colon cancer and T-cell acute lymphoblastic leukaemia (T-ALL). In line with these genomic data, engineered deletion of Fbw7 in mouse T cells results in T-ALL, validating FBW7 as a T-ALL tumour suppressor. Determining the precise molecular mechanisms by which FBW7 exerts antitumour activity is an area of intensive investigation. These mechanisms are thought to relate in part to FBW7-mediated destruction of key proteins relevant to cancer, including Jun, Myc, cyclin E and notch 1 (ref. 9), all of which have oncoprotein activity and are overexpressed in various human cancers, including leukaemia. In addition to accelerating cell growth, overexpression of Jun, Myc or notch 1 can also induce programmed cell death. Thus, considerable uncertainty surrounds how FBW7-deficient cells evade cell death in the setting of upregulated Jun, Myc and/or notch 1. Here we show that the E3 ubiquitin ligase SCF(FBW7) (a SKP1-cullin-1-F-box complex that contains FBW7 as the F-box protein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylation and destruction in a manner that depends on phosphorylation by glycogen synthase kinase 3. Human T-ALL cell lines showed a close relationship between FBW7 loss and MCL1 overexpression. Correspondingly, T-ALL cell lines with defective FBW7 are particularly sensitive to the multi-kinase inhibitor sorafenib but resistant to the BCL2 antagonist ABT-737. On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mechanism that enables FBW7-deficient cells to evade apoptosis. Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7-deficient T-ALL.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076007/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076007/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Inuzuka, Hiroyuki -- Shaik, Shavali -- Onoyama, Ichiro -- Gao, Daming -- Tseng, Alan -- Maser, Richard S -- Zhai, Bo -- Wan, Lixin -- Gutierrez, Alejandro -- Lau, Alan W -- Xiao, Yonghong -- Christie, Amanda L -- Aster, Jon -- Settleman, Jeffrey -- Gygi, Steven P -- Kung, Andrew L -- Look, Thomas -- Nakayama, Keiichi I -- DePinho, Ronald A -- Wei, Wenyi -- GM089763/GM/NIGMS NIH HHS/ -- R01 GM089763/GM/NIGMS NIH HHS/ -- R01 GM089763-01/GM/NIGMS NIH HHS/ -- R01 GM089763-02/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Mar 3;471(7336):104-9. doi: 10.1038/nature09732.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21368833" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Apoptosis/drug effects ; Benzenesulfonates/pharmacology ; Biphenyl Compounds/pharmacology ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line, Tumor ; F-Box Proteins/genetics/*metabolism ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Mice ; Molecular Sequence Data ; Myeloid Cell Leukemia Sequence 1 Protein ; Niacinamide/analogs & derivatives ; Nitrophenols/pharmacology ; Phenylurea Compounds ; Phosphorylation ; Piperazines/pharmacology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Protein Binding/drug effects ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/*chemistry/*metabolism ; Pyridines/pharmacology ; SKP Cullin F-Box Protein Ligases/*chemistry/*metabolism ; Sulfonamides/pharmacology ; Tumor Suppressor Proteins/deficiency/genetics/metabolism ; Ubiquitin-Protein Ligases/deficiency/genetics/*metabolism ; *Ubiquitination/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2012-10-30
    Description: Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561483/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561483/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tachibana, Masahito -- Amato, Paula -- Sparman, Michelle -- Woodward, Joy -- Sanchis, Dario Melguizo -- Ma, Hong -- Gutierrez, Nuria Marti -- Tippner-Hedges, Rebecca -- Kang, Eunju -- Lee, Hyo-Sang -- Ramsey, Cathy -- Masterson, Keith -- Battaglia, David -- Lee, David -- Wu, Diana -- Jensen, Jeffrey -- Patton, Phillip -- Gokhale, Sumita -- Stouffer, Richard -- Mitalipov, Shoukhrat -- 8P51OD011092/OD/NIH HHS/ -- EY021214/EY/NEI NIH HHS/ -- HD057121/HD/NICHD NIH HHS/ -- HD059946/HD/NICHD NIH HHS/ -- HD063276/HD/NICHD NIH HHS/ -- P51 OD011092/OD/NIH HHS/ -- P51 RR000163/RR/NCRR NIH HHS/ -- R01 EY021214/EY/NEI NIH HHS/ -- R01 HD057121/HD/NICHD NIH HHS/ -- R01 HD059946/HD/NICHD NIH HHS/ -- R01 HD063276/HD/NICHD NIH HHS/ -- England -- Nature. 2013 Jan 31;493(7434):627-31. doi: 10.1038/nature11647. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103867" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Nucleus/genetics ; Cryopreservation ; Cytoplasm/genetics ; DNA, Mitochondrial/analysis/genetics ; Embryo, Mammalian/embryology ; Embryonic Stem Cells/cytology ; Female ; Fertilization ; *Genetic Therapy ; Humans ; Macaca mulatta/genetics/growth & development ; Microsatellite Repeats/genetics ; Mitochondrial Diseases/*genetics/*therapy ; Nuclear Transfer Techniques/*standards ; Oocytes/cytology ; Pregnancy ; Young Adult ; Zygote/cytology/pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-07-11
    Description: Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the 'gold standard', they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Hong -- Morey, Robert -- O'Neil, Ryan C -- He, Yupeng -- Daughtry, Brittany -- Schultz, Matthew D -- Hariharan, Manoj -- Nery, Joseph R -- Castanon, Rosa -- Sabatini, Karen -- Thiagarajan, Rathi D -- Tachibana, Masahito -- Kang, Eunju -- Tippner-Hedges, Rebecca -- Ahmed, Riffat -- Gutierrez, Nuria Marti -- Van Dyken, Crystal -- Polat, Alim -- Sugawara, Atsushi -- Sparman, Michelle -- Gokhale, Sumita -- Amato, Paula -- Wolf, Don P -- Ecker, Joseph R -- Laurent, Louise C -- Mitalipov, Shoukhrat -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 10;511(7508):177-83. doi: 10.1038/nature13551. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3]. ; 1] Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA [2]. ; 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Bioinformatics Program, University of California at San Diego, La Jolla, California 92093, USA. ; 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA. ; Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA. ; 1] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [2] Department of Obstetrics and Gynecology, South Miyagi Medical Center, Shibata-gun, Miyagi 989-1253, Japan (M.T.); Department of Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden (A.P.). ; Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA. ; University Pathologists LLC, Boston University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02118, USA. ; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA. ; 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Howard Hughes Medical Institute, the Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3] Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008523" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Cellular Reprogramming ; Chromosome Aberrations ; Chromosomes, Human, X/genetics/metabolism ; DNA Copy Number Variations ; DNA Methylation ; Genome-Wide Association Study ; Genomic Imprinting ; Humans ; Nuclear Transfer Techniques/standards ; Pluripotent Stem Cells/cytology/*metabolism ; Transcriptome
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  • 10
    Publication Date: 2010-03-12
    Description: Gene expression is an important phenotype that informs about genetic and environmental effects on cellular state. Many studies have previously identified genetic variants for gene expression phenotypes using custom and commercially available microarrays. Second generation sequencing technologies are now providing unprecedented access to the fine structure of the transcriptome. We have sequenced the mRNA fraction of the transcriptome in 60 extended HapMap individuals of European descent and have combined these data with genetic variants from the HapMap3 project. We have quantified exon abundance based on read depth and have also developed methods to quantify whole transcript abundance. We have found that approximately 10 million reads of sequencing can provide access to the same dynamic range as arrays with better quantification of alternative and highly abundant transcripts. Correlation with SNPs (small nucleotide polymorphisms) leads to a larger discovery of eQTLs (expression quantitative trait loci) than with arrays. We also detect a substantial number of variants that influence the structure of mature transcripts indicating variants responsible for alternative splicing. Finally, measures of allele-specific expression allowed the identification of rare eQTLs and allelic differences in transcript structure. This analysis shows that high throughput sequencing technologies reveal new properties of genetic effects on the transcriptome and allow the exploration of genetic effects in cellular processes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836232/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836232/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Montgomery, Stephen B -- Sammeth, Micha -- Gutierrez-Arcelus, Maria -- Lach, Radoslaw P -- Ingle, Catherine -- Nisbett, James -- Guigo, Roderic -- Dermitzakis, Emmanouil T -- 077046/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Apr 1;464(7289):773-7. doi: 10.1038/nature08903. Epub 2010 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211 Switzerland. stephen.montgomery@unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20220756" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Alternative Splicing/genetics ; European Continental Ancestry Group/*genetics ; Exons/genetics ; Gene Expression Profiling/*methods ; Haplotypes/genetics ; Homozygote ; Humans ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; RNA, Messenger/*analysis/*genetics ; Sequence Analysis, DNA/*methods
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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