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==Gene knockout by mutation== Gene knockout by mutation is commonly carried out in bacteria. An early instance of the use of this technique in ''Escherichia coli'' was published in 1989 by Hamilton, et al.<ref name= Hamilton >{{cite journal |date=September 1989 |vauthors=Hamilton CM, Aldea M, Washburn BK, Babitzke P, Kushner SR |title=New method for generating deletions and gene replacements in ''Escherichia coli'' |journal=Journal of Bacteriology |volume=171 |issue=9 |pages=4617β4622 |doi=10.1128/jb.171.9.4617-4622.1989 |doi-access=free|pmid=2548993 |pmc=210259 }}</ref> In this experiment, two sequential recombinations were used to delete the gene. This work established the feasibility of removing or replacing a functional gene in bacteria. That method has since been developed for other organisms, particularly research animals, like mice. Knockout mice are commonly used to study genes with human equivalents that may have significance for disease. An example of a study using knockout mice is an investigation of the roles of [[XIRP2|Xirp]] proteins in Sudden Unexplained Nocturnal Death Syndrome (SUNDS) and Brugada Syndrome in the Chinese Han Population.<ref name= Huang >{{cite journal |last=Huang |first=Lei |display-authors=etal |date=January 2018 |title=Critical Roles of Xirp Proteins in Cardiac Conduction and Their Rare Variants Identified in Sudden Unexplained Nocturnal Death Syndrome and Brugada Syndrome in Chinese Han Population |journal=J. Am. Heart Assoc. |volume=7 |issue=1 |doi=10.1161/JAHA.117.006320 |doi-access=free|pmid=29306897 |pmc=5778954 }}</ref>
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