Abstract：
:The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Cacheiro P,Muñoz-Fuentes V,Murray SA,Dickinson ME,Bucan M,Nutter LMJ,Peterson KA,Haselimashhadi H,Flenniken AM,Morgan H,Westerberg H,Konopka T,Hsu CW,Christiansen A,Lanza DG,Beaudet AL,Heaney JD,Fuchs H,Gailus-Durnerdoi
10.1038/s41467-020-14284-2subject
Has Abstractpub_date
2020-01-31 00:00:00pages
655issue
1issn
2041-1723pii
10.1038/s41467-020-14284-2journal_volume
11pub_type
杂志文章abstract：:The history of the Earth has been marked by major ecological transitions, driven by metabolic innovation, that radically reshaped the composition of the oceans and atmosphere. The nature and magnitude of the earliest transitions, hundreds of million years before photosynthesis evolved, remain poorly understood. Using ...
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