Ninette Cohen, PhD
- ASSOCIATE PROFESSOR | Genetics and Genomic Sciences
MSc, Tel Aviv University, Sackler School of Medicine
PhD, Tel Aviv University, Sackler School of Medicine
Mount Sinai School of Medicine
Research in the molecular cytogenetics laboratory is focused on chromosome rearrangement disorders and their mechanism of generation. Most chromosome rearrangements occur sporadically in the population at a specific frequency, depending on the disorder. The combined frequency of chromosome rearrangements, balanced and unbalanced, including translocations, deletions, duplications and inversions is estimated at 1 in 300 live births. For many of these disorders, genomic architecture plays an important role in susceptibility to rearrangement.
We are currently investigating the mechanism that generates the isodicentric Xq chromosome (idic(Xq)), a spontaneously occurring chromosomal aberration that is present in 18% of Turner Syndrome cases, and is the most common constitutional isochromosome in humans. We have collected a number of cell lines to delineate the breakpoints of the idic(Xq) in order to better understand how the architecture in the region of Xp11 influences formation of the isochromosome. Our methods of study include FISH and array CGH, generation of human hamster somatic hybrid cell lines, pulse field gel electrophoresis and long range PCR to amplify across breakpoint junctions. Ultimately, we would like to determine whether specific variations in genomic architecture at the breakpoint regions of recurrent rearrangements confer increased susceptibility to the rearrangement. The laboratory is also involved in a collaborative effort to understand how chromosome rearrangement disorders contribute to autism by investigating the frequency of known microdeletion and microduplication syndromes in autism patients as well as delineating novel de novo rearrangements in autism.
Cytogenetics and Cytogenomics laboratory
Our Cytogenetics and Cytogenomics laboratory analyzes human chromosomes from amniotic fluid and chorionic villi (prenatal chromosome analysis), peripheral blood and skin biopsy for congenital anomalies, infertility, or other indications, and products of conception. In addition the laboratory offers both prenatal and postnatal Fluorescence in Situ Hybridization (FISH) analysis for a number of chromosome disorders, including DiGeorge syndrome, Williams syndrome, Prader Willi and Angelman syndromes, Wolf-Hirschhorn syndrome, Cri-du-Chat syndrome, Smith Magenis syndrome and Miller-Dieker syndrome. Our laboratory will be soon offering the newest molecular cytogenetics technique, array Comparative Genomic Hybridization (array-CGH) for the detection of chromosomal imbalances in individuals with unexplained mental retardation, developmental delay, autism spectrum disorders with/without multiple congenital anomalies. This novel technology will increase our ability to clinically detect chromosomal rearrangements that are not visible by standard karyotype analysis but involve genomic copy number changes. A whole genome array will be applied on postnatal samples while a more specific targeted array is being designed for prenatal testing.
Trakhtenbrot L, Cohen N, Betts DR, Niggli FK, Amariglio N, Brok-Simoni F, Rechavi G, Meitar D. Interphase fluorescence in situ hybridization detection of chromosome 17 and 17q region gains in neuroblastoma: are they secondary events?. Cancer genetics and cytogenetics 2002 Sep; 137(2).
Cohen N, Trakhtenbrot L, Yukla M, Manor Y, Gaber E, Yosef G, Amariglio N, Rechavi G, Amiel A. SKY detection of chromosome rearrangements in two cases of tMDS with a complex karyotype. Cancer genetics and cytogenetics 2002 Oct; 138(2).
Cohen N, Amariglio N, Rechavi G, Trakhtenbrot L, Hardan I. Simultaneous detection of deletions of 9q and 22q in a subgroup of chronic myelocytic leukemia Philadelphia-positive patients by a novel probe. Cancer genetics and cytogenetics 2003 Feb; 141(1).
Cohen N, Betts DR, Rechavi G, Amariglio N, Trakhtenbrot L. Clonal expansion and not cell interconversion is the basis for the neuroblast and nonneuronal types of the SK-N-SH neuroblastoma cell line. Cancer genetics and cytogenetics 2003 May; 143(1).
Hardan I, Rothman R, Gelibter A, Cohen N, Shimoni A, Sokolovsky M, Reichart M, Ishoev G, Amariglio N, Rechavi G, Nagler A, Trakhtenbrot L. Determination of chromosome 13 status in bone marrow cells of patients with multiple myeloma using combined morphologic and fluorescence in situ hybridization analysis. Experimental hematology 2004 Mar; 32(3).
Cohen N, Betts DR, Tavori U, Toren A, Ram T, Constantini S, Grotzer MA, Amariglio N, Rechavi G, Trakhtenbrot L. Karyotypic evolution pathways in medulloblastoma/primitive neuroectodermal tumor determined with a combination of spectral karyotyping, G-banding, and fluorescence in situ hybridization. Cancer genetics and cytogenetics 2004 Feb; 149(1).
Betts DR, Cohen N, Leibundgut KE, Kühne T, Caflisch U, Greiner J, Traktenbrot L, Niggli FK. Characterization of karyotypic events and evolution in neuroblastoma. Pediatric blood & cancer 2005 Feb; 44(2).
Kneller A, Cohen N, Berkowicz M, Reichart M, Rosner E, Sokolovski M, Nagler A, Rechavi G, Amariglio N, Trakhtenbrot L. Acquisition of a Ph chromosome with minor BCR/ABL fusion in treatment-related myelodysplastic syndrome with chromosome 7 abnormalities in a patient treated for Hodgkin disease. Cancer genetics and cytogenetics 2005 May; 159(1).
Edelmann L, Prosnitz A, Pardo S, Bhatt J, Cohen N, Lauriat T, Ouchanov L, González PJ, Manghi ER, Bondy P, Esquivel M, Monge S, Delgado MF, Splendore A, Francke U, Burton BK, McInnes LA. An atypical deletion of the Williams-Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism. Journal of medical genetics 2007 Feb; 44(2).
Stanchescu R, Betts DR, Yekutieli D, Ambros P, Cohen N, Rechavi G, Amariglio N, Trakhtenbrot L. SKY analysis of childhood neural tumors and cell lines demonstrates a susceptibility of aberrant chromosomes to further rearrangements. Cancer letters 2007 May; 250(1).
Betts DR, Stanchescu R, Niggli FK, Cohen N, Rechavi G, Amariglio N, Trakhtenbrot L. SKY reveals a high frequency of unbalanced translocations involving chromosome 6 in t(12;21)-positive acute lymphoblastic leukemia. Leukemia research 2008 Jan; 32(1).
Pardo S, Blitman N, Han B, Cohen N, Edelmann L, Hirschhorn K. Multiple hemangiomas in a patient with a t(3q;4p) translocation: an infrequent association with Wolf-Hirschhorn syndrome. American journal of medical genetics. Part A 2008 Jan; 146A(2).
Cai G, Edelmann L, Goldsmith JE, Cohen N, Nakamine A, Reichert JG, Hoffman EJ, Zurawiecki DM, Silverman JM, Hollander E, Soorya L, Anagnostou E, Betancur C, Buxbaum JD. Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: efficient identification of known microduplications and identification of a novel microduplication in ASMT. BMC medical genomics 2008; 1.
Scott SA, Cohen N, Brandt T, Toruner G, Desnick RJ, Edelmann L. Detection of low-level mosaicism and placental mosaicism by oligonucleotide array comparative genomic hybridization. Genetics in medicine : official journal of the American College of Medical Genetics 2010 Feb; 12(2).
Carvajal-Vergara X, Sevilla A, D'Souza SL, Ang YS, Schaniel C, Lee DF, Yang L, Kaplan AD, Adler ED, Rozov R, Ge Y, Cohen N, Edelmann LJ, Chang B, Waghray A, Su J, Pardo S, Lichtenbelt KD, Tartaglia M, Gelb BD, Lemischka IR. Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 2010 Jun; 465(7299).
Scott SA, Cohen N, Brandt T, Warburton PE, Edelmann L. Large inverted repeats within Xp11.2 are present at the breakpoints of isodicentric X chromosomes in Turner syndrome. Human molecular genetics 2010 Sep; 19(17).
Brandt T, Desai K, Grodberg D, Mehta L, Cohen N, Tryfon A, Kolevzon A, Soorya L, Buxbaum JD, Edelmann L. Complex autism spectrum disorder in a patient with a 17q12 microduplication. American journal of medical genetics. Part A 2012 May; 158A(5).
Peled A, Hardan I, Trakhtenbrot L, Gur E, Magid M, Darash-Yahana M, Cohen N, Grabovsky V, Franitza S, Kollet O, Lider O, Alon R, Rechavi G, Lapidot T. Immature leukemic CD34+CXCR4+ cells from CML patients have lower integrin-dependent migration and adhesion in response to the chemokine SDF-1. Stem cells (Dayton, Ohio) 2002; 20(3).
Brandt T, Blanchard L, Desai K, Nimkarn S, Cohen N, Edelmann L, Mehta L. 46,XY disorder of sex development and developmental delay associated with a novel 9q33.3 microdeletion encompassing NR5A1. European journal of medical genetics 2013 Nov; 56(11).