biostudies-literatureLim CSState Major Research and Development Program of ChinaNICHD NIH HHSHoward Hughes Medical InstituteNIMH NIH HHSNational Institute of HealthNational Natural Science Foundation of ChinaNIAAA NIH HHSNINDS NIH HHSChinese Ministry of EducationNational Honor Scientist Program of KoreaRobert Wood Johnson FoundationJapan Society for the Promotion of Science537-552https://www.ebi.ac.uk/biostudies/studies/S-EPMC5393050biostudies-literatureUnknown31(6)Rapid advances in genetics are linking mutations on genes to diseases at an exponential rate, yet characterizing the gene-mutation-cell-behavior relationships essential for precision medicine remains a daunting task. More than 350 mutations on small GTPase <i>BRaf</i> are associated with various tumors, and ∼40 mutations are associated with the neurodevelopmental disorder cardio-facio-cutaneous syndrome (CFC). We developed a fast cost-effective lentivirus-based rapid gene replacement method to interrogate the physiopathology of BRaf and ∼50 disease-linked BRaf mutants, including all CFC-linked mutants. Analysis of simultaneous multiple patch-clamp recordings from 6068 pairs of rat neurons with validation in additional mouse and human neurons and multiple learning tests from 1486 rats identGenes & developmentBRaf signaling principles unveiled by large-scale human mutation analysis with a rapid lentivirus-based gene replacement method.PMC5393050AA023797R01 NS089578R37 NS036715R01 NS092548NSFC81625006MH64856NSFC31471024NS089578NSFC30728012NRF2016R1D1A1B03931525R01 AA023797NS065183F30 MH108321MH108321R01 NS053570R00 NS065183R01 MH064856R21 NS094980NS053570R01 HD064743R01 NS036715K99 NS065183NS091452NS092548HD064743R01 NS091452NRF2012R1A3A1050385B13026NS0367152016YFA0500400Araki YKang XChang QZhang HLim CSChoi SWang SHoang ETPang ZPZhu JJBu QMirabella VShen YKaang BKHuganir RLfalseBRaf signaling principles unveiled by large-scale human mutation analysis with a rapid lentivirus-based gene replacement method.Rapid advances in genetics are linking mutations on genes to diseases at an exponential rate, yet characterizing the gene-mutation-cell-behavior relationships essential for precision medicine remains a daunting task. More than 350 mutations on small GTPase <i>BRaf</i> are associated with various tumors, and ∼40 mutations are associated with the neurodevelopmental disorder cardio-facio-cutaneous syndrome (CFC). We developed a fast cost-effective lentivirus-based rapid gene replacement method to interrogate the physiopathology of BRaf and ∼50 disease-linked BRaf mutants, including all CFC-linked mutants. Analysis of simultaneous multiple patch-clamp recordings from 6068 pairs of rat neurons with validation in additional mouse and human neurons and multiple learning tests from 1486 rats ident2017-01-01T00:00:00Z2017 Mar2026-05-30T08:56:17.351Z2019-03-27T02:41:24ZS-EPMC53930502840462910.1101/gad.294413.116