ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2015-03-26
    Description: Autism is a multifactorial neurodevelopmental disorder affecting more males than females; consequently, under a multifactorial genetic hypothesis, females are affected only when they cross a higher biological threshold. We hypothesize that deleterious variants at conserved residues are enriched in severely affected patients arising from female-enriched multiplex families with severe disease, enhancing the detection of key autism genes in modest numbers of cases. Here we show the use of this strategy by identifying missense and dosage sequence variants in the gene encoding the adhesive junction-associated delta-catenin protein (CTNND2) in female-enriched multiplex families and demonstrating their loss-of-function effect by functional analyses in zebrafish embryos and cultured hippocampal neurons from wild-type and Ctnnd2 null mouse embryos. Finally, through gene expression and network analyses, we highlight a critical role for CTNND2 in neuronal development and an intimate connection to chromatin biology. Our data contribute to the understanding of the genetic architecture of autism and suggest that genetic analyses of phenotypic extremes, such as female-enriched multiplex families, are of innate value in multifactorial disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383723/" 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/PMC4383723/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turner, Tychele N -- Sharma, Kamal -- Oh, Edwin C -- Liu, Yangfan P -- Collins, Ryan L -- Sosa, Maria X -- Auer, Dallas R -- Brand, Harrison -- Sanders, Stephan J -- Moreno-De-Luca, Daniel -- Pihur, Vasyl -- Plona, Teri -- Pike, Kristen -- Soppet, Daniel R -- Smith, Michael W -- Cheung, Sau Wai -- Martin, Christa Lese -- State, Matthew W -- Talkowski, Michael E -- Cook, Edwin -- Huganir, Richard -- Katsanis, Nicholas -- Chakravarti, Aravinda -- 1U24MH081810/MH/NIMH NIH HHS/ -- 5R25MH071584-07/MH/NIMH NIH HHS/ -- MH095867/MH/NIMH NIH HHS/ -- MH19961-14/MH/NIMH NIH HHS/ -- R00 MH095867/MH/NIMH NIH HHS/ -- R01 DK075972/DK/NIDDK NIH HHS/ -- R01 MH060007/MH/NIMH NIH HHS/ -- R01 MH074090/MH/NIMH NIH HHS/ -- R01MH074090/MH/NIMH NIH HHS/ -- R01MH081754/MH/NIMH NIH HHS/ -- England -- Nature. 2015 Apr 2;520(7545):51-6. doi: 10.1038/nature14186. Epub 2015 Mar 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Predoctoral Training Program in Human Genetics and Molecular Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] National Institute of Mental Health (NIMH) Autism Centers of Excellence (ACE) Genetics Consortium at the University of California, Los Angeles, Los Angeles, California 90095, USA. ; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Center for Human Disease Modeling, Duke University, Durham, North Carolina 27710, USA. ; Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; 1] Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] National Institute of Mental Health (NIMH) Autism Centers of Excellence (ACE) Genetics Consortium at the University of California, Los Angeles, Los Angeles, California 90095, USA. ; 1] Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA [2] Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 USA. ; 1] National Institute of Mental Health (NIMH) Autism Centers of Excellence (ACE) Genetics Consortium at the University of California, Los Angeles, Los Angeles, California 90095, USA [2] Department of Psychiatry, University of California, San Francisco, San Francisco, California 94158, USA. ; 1] National Institute of Mental Health (NIMH) Autism Centers of Excellence (ACE) Genetics Consortium at the University of California, Los Angeles, Los Angeles, California 90095, USA [2] Department of Psychiatry, Yale University, New Haven, Connecticut 06511, USA. ; Leidos Biomedical Research, Inc., Frederick, Maryland 21702, USA. ; National Human Genome Research Institute, Bethesda, Maryland 20892, USA. ; Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] National Institute of Mental Health (NIMH) Autism Centers of Excellence (ACE) Genetics Consortium at the University of California, Los Angeles, Los Angeles, California 90095, USA [2] Autism &Developmental Medicine Institute, Geisinger Health System, Lewisburg, Pennsylvania 17837, USA. ; University of Illinois at Chicago, Chicago, Illinois 60608, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25807484" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*genetics/*metabolism ; Brain/embryology/*metabolism ; Catenins/*deficiency/*genetics/metabolism ; Cells, Cultured ; Chromatin/genetics/metabolism ; DNA Copy Number Variations/genetics ; Embryo, Mammalian/cytology/metabolism ; Exome/genetics ; Female ; Gene Expression ; Gene Expression Regulation, Developmental ; Hippocampus/pathology ; Humans ; Male ; Mice ; Models, Genetic ; Multifactorial Inheritance/genetics ; Mutation, Missense ; Nerve Net ; Neurons/cytology/metabolism ; Sex Characteristics ; Zebrafish/embryology/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2015-09-01
    Description: Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell-derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and beta-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618316/" 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/PMC4618316/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hinson, John T -- Chopra, Anant -- Nafissi, Navid -- Polacheck, William J -- Benson, Craig C -- Swist, Sandra -- Gorham, Joshua -- Yang, Luhan -- Schafer, Sebastian -- Sheng, Calvin C -- Haghighi, Alireza -- Homsy, Jason -- Hubner, Norbert -- Church, George -- Cook, Stuart A -- Linke, Wolfgang A -- Chen, Christopher S -- Seidman, J G -- Seidman, Christine E -- EB017103/EB/NIBIB NIH HHS/ -- HG005550/HG/NHGRI NIH HHS/ -- HL007374/HL/NHLBI NIH HHS/ -- HL115553/HL/NHLBI NIH HHS/ -- HL125807/HL/NHLBI NIH HHS/ -- K08 HL125807/HL/NHLBI NIH HHS/ -- T32 HL007208/HL/NHLBI NIH HHS/ -- Department of Health/United Kingdom -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):982-6. doi: 10.1126/science.aaa5458.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. jthinson@partners.org cseidman@genetics.med.harvard.edu. ; Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA. The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA. ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ; Department of Cardiovascular Physiology, Ruhr University Bochum, MA 3/56 D-44780, Bochum, Germany. ; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Cardiovascular and Metabolic Sciences, Max Delbruck Center for Molecular Medicine, Berlin, Germany. ; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. ; Cardiovascular and Metabolic Sciences, Max Delbruck Center for Molecular Medicine, Berlin, Germany. DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany. ; National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease at Royal Brompton and Harefield National Health Service (NHS) Foundation Trust, Imperial College London, London, UK. National Heart Centre and Duke-National University, Singapore, Singapore. ; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. jthinson@partners.org cseidman@genetics.med.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315439" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-Agonists/pharmacology ; Cardiomyopathy, Dilated/*genetics/pathology/*physiopathology ; Cells, Cultured ; Connectin/chemistry/*genetics/*physiology ; Heart Rate ; Humans ; Induced Pluripotent Stem Cells/*physiology ; Isoproterenol/pharmacology ; Mutant Proteins/chemistry/physiology ; *Mutation, Missense ; Myocardial Contraction ; Myocytes, Cardiac/*physiology ; RNA/genetics/metabolism ; Sarcomeres/*physiology/ultrastructure ; Sequence Analysis, RNA ; Signal Transduction ; Stress, Physiological
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2015-05-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook-Andersen, Heidi -- Wilkinson, Miles F -- K12 HD001259/HD/NICHD NIH HHS/ -- T32 HD007203/HD/NICHD NIH HHS/ -- England -- Nature. 2015 May 21;521(7552):300-1. doi: 10.1038/nature14524. Epub 2015 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Reproductive Medicine, University of California, San Diego, La Jolla, California, 92093, USA. ; 1] Department of Reproductive Medicine, University of California, San Diego, La Jolla, California, 92093, USA. [2] Institute of Genomic Medicine, University of California, San Diego.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25970243" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Humans ; Male ; RNA Splicing/*genetics ; Vertebrates/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...