RAG1

Because of these effects, Rag1 deletion is used in mouse models of disease to impair T cell and B cell development, and functionally deletes mature T and B cells from the immune system.^[8]

In humans, RAG deficiency was first recognised as a form of immune dysregulation known as Omenn syndrome. RAG deficiency is considered an autosomal recessive disease. The disorder is generally identified in infants. Complete loss-of-function in RAG1/2, the main components responsible for V(D)J recombination activity, produces severe immunodeficiency in humans. Hypomorphic RAG variants can retain partial recombination activity^[9] and result in a distinct phenotype of combined immunodeficiency with granuloma and/or autoimmunity (CID-G/A),^[10][11][12] as well as other milder forms, such as antibody deficiency,^[13] Idiopathic CD4⁺ T lymphopenia ^[14] or vasculitis.^[15] RAG deficiency can be measured by in vitro quantification of recombination activity.^[16][17][18] 71 RAG1 and 39 RAG2 variants have been functionally assayed to date (2019) (less than 10% of the potential point mutations that may cause disease). However, top candidate variants have been ranked by their predicted clinical relevance.^[6]

RAG1 is frequently used as a marker in phylogenetic studies. That is, RAG1 sequences are often used to construct phylogenetic trees in order to investigate the relationships between species or higher taxa. Although the selection of RAG1 was somewhat arbitrary, it is one of several universal nuclear protein-coding loci (NPCL) that are applicable across diverse taxa and show good phylogenetic discrimination. For instance, RAG1 has been successfully used to make phylogenetic inferences within all major groups of fish and reptiles.^[19][20] In many cases, RAG1 is used together with mitochondrial sequences as these evolve much faster and thus provide information about more closely related taxa.^[21] A combination of nuclear and mitochondrial DNA is usually recommended due to fact that they may yield discrepant phylogenetic relationships, a phenomenon called mito-nuclear discordance.^[22]