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Lethal phenotypes in Mendelian disorders.
Cacheiro, Pilar; Lawson, Samantha; Van den Veyver, Ignatia B; Marengo, Gabriel; Zocche, David; Murray, Stephen A; Duyzend, Michael; Robinson, Peter N; Smedley, Damian.
Afiliação
  • Cacheiro P; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
  • Lawson S; ITS Research, Queen Mary University of London, London, United Kingdom.
  • Van den Veyver IB; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX.
  • Marengo G; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
  • Zocche D; North West Thames Regional Genetics Service, Northwick Park and St Mark's Hospitals, London, United Kingdom.
  • Murray SA; The Jackson Laboratory, Bar Harbor, ME.
  • Duyzend M; Massachusetts General Hospital, Boston, MA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA; Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA.
  • Robinson PN; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Smedley D; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. Electronic address: d.smedley@qmul.ac.uk.
Genet Med ; 26(7): 101141, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38629401
ABSTRACT

PURPOSE:

Existing resources that characterize the essentiality status of genes are based on either proliferation assessment in human cell lines, viability evaluation in mouse knockouts, or constraint metrics derived from human population sequencing studies. Several repositories document phenotypic annotations for rare disorders; however, there is a lack of comprehensive reporting on lethal phenotypes.

METHODS:

We queried Online Mendelian Inheritance in Man for terms related to lethality and classified all Mendelian genes according to the earliest age of death recorded for the associated disorders, from prenatal death to no reports of premature death. We characterized the genes across these lethality categories, examined the evidence on viability from mouse models and explored how this information could be used for novel gene discovery.

RESULTS:

We developed the Lethal Phenotypes Portal to showcase this curated catalog of human essential genes. Differences in the mode of inheritance, physiological systems affected, and disease class were found for genes in different lethality categories, as well as discrepancies between the lethal phenotypes observed in mouse and human.

CONCLUSION:

We anticipate that this resource will aid clinicians in the diagnosis of early lethal conditions and assist researchers in investigating the properties that make these genes essential for human development.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Genes Letais / Doenças Genéticas Inatas Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Genes Letais / Doenças Genéticas Inatas Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article