Potential sources of negative effects of gene editing in animals

Gene editing is becoming increasingly widespread in work with farm animals. However, the limited number of genes and traits used as editing targets suggests the need to develop methods for predicting the negative effects of this method, associated with the characteristics of the selected target genes. In this purpose, in the present work, we compared the evolutionary conservation of synteny and is tissue-specific and most widely used to increase the rate of live weight gain (A.V. Ledesma, A.L. Van Eenennaam, 2024). The leptin receptor gene (LEPR) is expressed in different tissues and affects energy metabolism and growth of animals (X. Wang et al., 2022). The gene GALNT17 encodes a member of the glycosylating enzyme superfamily of N-acetylgalactosaminyltransferases, and is associated with the social behavior of animals (C.Y. Chen et al., 2022). In humans, GALNT17 is configured into the chromatin loop with two other regulatory-related genes, encoding calcium-binding protein 8 (CALN1 , calneuron 1) and transcription activator AUTS2 (autism susceptibility gene 2 protein) (N. Gheldof et al., 2013). Gene editing of LEPR and GALNT17 , unlike MSTN , caused high mortality of animals (K.A. Pennington et al., 2022; C.Y. Chen et al., 2022). For LEPR and GALNT17 , unlike MSTN , evolutionarily conservative genetic linkages with a number of neighboring genes are identified in mammals, birds and reptiles which increases the likelihood of pleiotropic effects of editing LEPR and GALNT17 . Apparently, in order to reduce undesirable effects when choosing target genes for editing, it is necessary to avoid genes with expression in a large number of tissues, and involved in signaling networks like LEPR and in an evolutionarily conservative gene blocks as in case of GALNT17 .