Evidence map›Paper›PMID 27745839›Full record

ArticleAmerican journal of human genetics2016

Structural Chromosomal Rearrangements Require Nucleotide-Level Resolution: Lessons from Next-Generation Sequencing in Prenatal Diagnosis.

Zehra Ordulu, Tammy Kammin, Harrison Brand, Vamsee Pillalamarri, Claire E Redin, Ryan L Collins, Ian Blumenthal, Carrie Hanscom, Shahrin Pereira, India Bradley and 18 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
37.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 97 citations in OpenAlex.

  1. Article
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  8. Reproductive outcomes in individuals with chromosomal reciprocal translocations.Genetics in medicine : official journal of the American College of Medical Genetics · 2021
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  19. Structural variation in the 3D genome.Nature reviews. Genetics · 2018
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 14 institutions in 3 countries.

Zehra OrduluDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Tammy KamminDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Harrison BrandCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA 02142, USA.
Vamsee PillalamarriCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Claire E RedinHarvard Medical School, Boston, MA 02115, USA; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA 02142, USA.
Ryan L CollinsCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Ian BlumenthalCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Carrie HanscomCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Shahrin PereiraDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA.
India BradleyDepartment of Psychiatry, Prenatal Diagnosis Center, David Geffen School of Medicine, University of California, Los Angeles, Medical Plaza, Los Angeles, CA 90095, USA.
Barbara F CrandallDepartment of Psychiatry, Prenatal Diagnosis Center, David Geffen School of Medicine, University of California, Los Angeles, Medical Plaza, Los Angeles, CA 90095, USA.
Pamela GerrolDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Mark A HaydenDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Naveed HussainDepartment of Pediatrics, Connecticut Children's Medical Center, University of Connecticut, Farmington, CT 06030, USA.
Bibi Kanengisser-PinesDepartment of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot 76100, Israel.
Sibel KantarciDepartment of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Brynn LevyDepartment of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Michael J MaceraNew York Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA.
Fabiola Quintero-RiveraDepartment of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Erica SpiegelDepartment of Maternal Fetal Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Blair StevensDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Medical School at Houston, Houston, TX 77030, USA.
Janet E UlmRegional Obstetrical Consultants, Chattanooga, TN 37403, USA.
Dorothy WarburtonDepartment of Genetics and Development, Columbia University, New York, NY 10032, USA; Department of Pediatrics, Columbia University, New York, NY 10032, USA.
Louise E Wilkins-HaugDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Naomi YachelevichDepartment of Pediatrics, Clinical Genetics Services, New York University School of Medicine, New York, NY 10003, USA.
James F GusellaCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA 02142, USA; Department of Genetics, Harvard Medical School, Boson, MA 02115, USA.
Michael E TalkowskiHarvard Medical School, Boston, MA 02115, USA; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA 02142, USA; Departments of Psychiatry and Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Cynthia C MortonDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA 02142, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Evolution and Genomic Science, School of Biological Sciences, University of Manchester, Manchester Academic Health Science Center, Manchester 03101, UK. Electronic address: cmorton@partners.org.
Brigham and Women's Hospital · USUniversity of California, Los Angeles · USBroad Institute · USCenter for Human Genetics · USColumbia University · USMassachusetts General Hospital · USColumbia University Irving Medical Center · USHarvard University · USKaplan Medical Center · ILNew York Hospital Queens · USPediatrics and Genetics · USRegional Obstetrical Consultants · USUniversity of Connecticut · USUniversity of Manchester · GB

Funding

RAPID GENE DISCOVERYP01GM061354 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI MORTON, CYNTHIA CASSON · 2001 to 2019
$24.3M
TRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0M
Clinical Diagnostic Sequencing of Structural VariationR01HD081256 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2015 to 2025
$7.2M
New Computational Methods and Emerging Technologies in Prenatal Genetic DiagnosisF32HD085857 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI BRAND, HARRISON · 2016 to 2016
$60k
NICHD NIH HHS F32 HD085857NICHD NIH HHS R01 HD081256NIGMS NIH HHS P01 GM061354NIGMS NIH HHS T32 GM007748
6 · The paper itself

Abstract

In this exciting era of "next-gen cytogenetics," integrating genomic sequencing into the prenatal diagnostic setting is possible within an actionable time frame and can provide precise delineation of balanced chromosomal rearrangements at the nucleotide level. Given the increased risk of congenital abnormalities in newborns with de novo balanced chromosomal rearrangements, comprehensive interpretation of breakpoints could substantially improve prediction of phenotypic outcomes and support perinatal medical care. Herein, we present and evaluate sequencing results of balanced chromosomal rearrangements in ten prenatal subjects with respect to the location of regulatory chromatin domains (topologically associated domains [TADs]). The genomic material from all subjects was interpreted to be "normal" by microarray analyses, and their rearrangements would not have been detected by cell-free DNA (cfDNA) screening. The findings of our systematic approach correlate with phenotypes of both pregnancies with untoward outcomes (5/10) and with healthy newborns (3/10). Two pregnancies, one with a chromosomal aberration predicted to be of unknown clinical significance and another one predicted to be likely benign, were terminated prior to phenotype-genotype correlation (2/10). We demonstrate that the clinical interpretation of structural rearrangements should not be limited to interruption, deletion, or duplication of specific genes and should also incorporate regulatory domains of the human genome with critical ramifications for the control of gene expression. As detailed in this study, our molecular approach to both detecting and interpreting the breakpoints of structural rearrangements yields unparalleled information in comparison to other commonly used first-tier diagnostic methods, such as non-invasive cfDNA screening and microarray analysis, to provide improved genetic counseling for phenotypic outcome in the prenatal setting.

Indexed as

Chromosome AberrationsGene RearrangementAllelesChromosome MappingCongenital AbnormalitiesFemaleGene Expression RegulationGenetic TestingGenome, HumanGenomicsHigh-Throughput Nucleotide SequencingHumansKaryotypingMaleNucleotidesPregnancyNucleotidesSOX9 protein, humanSOX9 Transcription Factor

Identifiers

PMID27745839
PMCPMC5097935
OpenAlexW2530792283

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.