Evidence map›Paper›PMID 26166479›Full record

ReviewAmerican journal of human genetics2015

The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.

Jessica X Chong, Kati J Buckingham, Shalini N Jhangiani, Corinne Boehm, Nara Sobreira, Joshua D Smith, Tanya M Harrell, Margaret J McMillin, Wojciech Wiszniewski, Tomasz Gambin and 33 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 369 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
369citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

369 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Genetics of Idiopathic Hypogonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2026
    Review
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  11. Advances in the Basic Sciences in Thoracic Oncology in the Last 20 Years and Their Translational Impact.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

309 more citing papers are in PubMed but not listed here.

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

43 authors.

Jessica X ChongDepartment of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Kati J BuckinghamDepartment of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Shalini N JhangianiHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Corinne BoehmMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nara SobreiraMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Joshua D SmithDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Tanya M HarrellDepartment of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Margaret J McMillinDepartment of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Wojciech WiszniewskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Tomasz GambinDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Zeynep H Coban AkdemirDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Kimberly DohenyMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Inherited Disease Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Alan F ScottMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dimitri AvramopoulosMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Aravinda ChakravartiMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Julie Hoover-FongMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Debra MathewsJohns Hopkins Berman Institute of Bioethics, Baltimore, MD 21205, USA.
P Dane WitmerMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Inherited Disease Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hua LingMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Inherited Disease Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kurt HetrickMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Inherited Disease Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lee WatkinsMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Inherited Disease Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Karynne E PattersonDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Frederic ReinierDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Elizabeth BlueDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Donna MuznyHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Martin KircherDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Kaya BilguvarDepartment of Genetics and Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, CT 06510, USA.
Francesc López-GiráldezDepartment of Genetics and Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, CT 06510, USA.
V Reid SuttonDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Holly K TaborDepartment of Pediatrics, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Suzanne M LealDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Murat GunelDepartment of Genetics and Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, CT 06510, USA.
Shrikant ManeDepartment of Genetics and Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, CT 06510, USA.
Richard A GibbsHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Eric BoerwinkleHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Ada HamoshMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
James R LupskiHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Richard P LiftonDepartment of Genetics and Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
David ValleMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Deborah A NickersonDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Centers for Mendelian Genomics
Michael J BamshadDepartment of Pediatrics, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Division of Genetic Medicine, Seattle Children's Hospital, Seattle, WA 98105, USA. Electronic address: mbamshad@uw.edu.

Funding

UW Center for Mendelian GenomicsU54HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, NICKERSON, DEBORAH A · 2012 to 2015
$20.0M
Baylor-Johns Hopkins Center for Mendelian GeneticsU54HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2012 to 2015
$15.6M
UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
Yale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8M
Baylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5M
Yale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0M
Howard Hughes Medical InstituteNHGRI NIH HHS HG006493NHGRI NIH HHS HG006504NHGRI NIH HHS HG006542NHGRI NIH HHS U54 HG006493NHGRI NIH HHS U54 HG006504NHGRI NIH HHS U54 HG006542NHGRI NIH HHS UM1 HG006493NHGRI NIH HHS UM1 HG006504NHGRI NIH HHS UM1 HG006542
6 · The paper itself

Abstract

Discovering the genetic basis of a Mendelian phenotype establishes a causal link between genotype and phenotype, making possible carrier and population screening and direct diagnosis. Such discoveries also contribute to our knowledge of gene function, gene regulation, development, and biological mechanisms that can be used for developing new therapeutics. As of February 2015, 2,937 genes underlying 4,163 Mendelian phenotypes have been discovered, but the genes underlying ∼50% (i.e., 3,152) of all known Mendelian phenotypes are still unknown, and many more Mendelian conditions have yet to be recognized. This is a formidable gap in biomedical knowledge. Accordingly, in December 2011, the NIH established the Centers for Mendelian Genomics (CMGs) to provide the collaborative framework and infrastructure necessary for undertaking large-scale whole-exome sequencing and discovery of the genetic variants responsible for Mendelian phenotypes. In partnership with 529 investigators from 261 institutions in 36 countries, the CMGs assessed 18,863 samples from 8,838 families representing 579 known and 470 novel Mendelian phenotypes as of January 2015. This collaborative effort has identified 956 genes, including 375 not previously associated with human health, that underlie a Mendelian phenotype. These results provide insight into study design and analytical strategies, identify novel mechanisms of disease, and reveal the extensive clinical variability of Mendelian phenotypes. Discovering the gene underlying every Mendelian phenotype will require tackling challenges such as worldwide ascertainment and phenotypic characterization of families affected by Mendelian conditions, improvement in sequencing and analytical techniques, and pervasive sharing of phenotypic and genomic data among researchers, clinicians, and families.

Indexed as

PhenotypeGenetic Diseases, InbornGenetics, MedicalHumansProteinsProteins

Identifiers

PMID26166479
PMCPMC4573249

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.