Gene Involved in V(D)J recombination and/or DNA repair

Abstract

The invention relates to a new gene and protein involved in V(D)J recombination and repair. The invention also relates to methods of diagnosis and therapy using these genes and protein. The invention also relates to transgenic animals over- and under-expressing said gene.

1 . A method for the determination of the type of severe combined immunodeficiency (SCID) in a patient comprising analyzing a nucleic acid selected from the group consisting of SEQ ID NO:1; nucleotides 39-2114 of SEQ ID NO:1; nucleotides 60-2114 of SEQ ID NO:1; nucleotides 39-1193 of SEQ ID NO:1; and nucleotides 60-1193 of SEQ ID NO:1;
 a mutation in said nucleic acid allowing the classification of said SCID as radiosensible SCID.   
     
     
         2 . The method of  claim 1 , wherein said mutation is selected from the group consisting of a point mutation that leads to a non-conservative change in an amino acid of the protein; a point mutation that produces a premature termination codon; and a deletion, an insertion, or modification in the genomic DNA corresponding to SEQ ID NO:1 or the splice donor and acceptor sites flanking the exons. 
     
     
         3 . The method of  claim 1 , wherein said mutation leads to the production of a non functional protein and wherein said mutation is selected from the group consisting of point mutations, deletions, insertions and mutations leading to incomplete splicing. 
     
     
         4 . The method of  claim 1 , wherein said mutation is selected from the mutations listed in Table 2. 
     
     
         5 . The method of  claim 1 , wherein said mutation is located in the splice donor and/or acceptor sites flanking the exons, which exons boundaries of the Artemis gene, and splices donor and acceptor sites are disclosed in the Table 1. 
     
     
         6 . A method of diagnosis in a patient, including a prenatal diagnosis, of a condition chosen from the group consisting of a SCID, a predisposition to cancer, an immune deficiency, and the carriage of a mutation increasing the risk of progeny to have such a disease, comprising analyzing a nucleic acid selected from the group consisting of SEQ ID NO:1, nucleotides 39-2114 of SEQ ID NO:1, nucleotides 60-2114 of SEQ ID NO:1, nucleotides 39-1193 of SEQ ID NO:1, and nucleotides 60-1193 of SEQ ID NO:1, and/or the protein ARTEMIS coded by said nucleic acid in said patient, a mutation in said nucleic acid and/or protein indicating a increased risk of having a SCID. 
     
     
         7 . The method of  claim 6 , wherein said method is for diagnosis of SCID. 
     
     
         8 . The method of  claim 6 , wherein said method is for diagnosis of radiosensible SCID (RS SCID). 
     
     
         9 . The method of  claim 6 , wherein said mutation is selected from the group consisting of point mutations that lead to a non-conservative change in an amino-acid of the protein or production of a premature termination codon, deletions, insertions, and modifications due to changes in the genomic DNA corresponding to SEQ ID NO:1, and the splice donor and acceptor sites flanking the exons. 
     
     
         10 . The method of  claim 10 , wherein said mutation leads to the production of a non functional protein and is selected from the group consisting of point mutations, deletions, insertions and mutations leading to incomplete splicing. 
     
     
         11 . The method of  claim 6 , wherein said mutation is selected in the mutations listed in Table 2. 
     
     
         12 . The method of  claim 6 , wherein said mutation is located in the splice donor and/or acceptor sites flanking the exons, which exons boundaries of the Artemis gene, and splices donor and acceptor sites are disclosed in the Table 1. 
     
     
         13 . The method of  claim 6 , wherein said analysis is performed on DNA obtained from cells harvested from the patient. 
     
     
         14 . The method of  claim 6 , wherein said analysis is performed on genomic DNA isolated from the patient with a pair of primers selected from the group consisting of SEQ ID NO:5 to SEQ ID NO:32, which primers are specific of sequences located in the introns of the Artemis gene and allow the amplification of the exons and of the junctions introns-exons.