Identification of pediatric onset inflammatory disease loci and methods of use thereof for the diagnosis and treatment of the same

Abstract

Compositions and methods for detection and treatment of inflammatory bowel disease are provided.

1 . A method for detecting a propensity for developing IBD, the method comprising: detecting the presence of a single nucleotide polymorphism on chromosome 20q13 in a target polynucleotide wherein if said single nucleotide polymorphism is present, said patient has an increased risk for developing IBD, wherein said single nucleotide polymorphism is a T at rs2315008 or an A at rs4809330 in the TNFRSF6B gene. 
     
     
         2 . A method for detecting a propensity for developing inflammatory bowel disease (IBD), the method comprising: detecting the presence of at least one single nucleotide polymorphism in a target polynucleotide wherein if said at least one single nucleotide polymorphism is present, said patient has an increased risk for developing IBD, wherein said at least one single nucleotide polymorphism is set forth in a Table selected from the group consisting of Table 6A, Table 6B, Table 13, Table 14, Table 15, Table 16, Table 17, Table 18, and Table 19. 
     
     
         3 . A method as claimed in  claim 1 , wherein the target nucleic acid is amplified prior to detection. 
     
     
         4 . The method of  claim 1 , wherein the step of detecting the presence of said single nucleotide polymorphism further comprises the step of analyzing a polynucleotide sample to determine the presence of said single nucleotide polymorphism by performing a process selected from the group consisting of detection of specific hybridization, measurement of allele size, restriction fragment length polymorphism analysis, allele-specific hybridization analysis, single base primer extension reaction, and sequencing of an amplified polynucleotide. 
     
     
         5 . A method as claimed in  claim 1 , wherein in the target nucleic acid is DNA. 
     
     
         6 . The method of  claim 1 , wherein nucleic acids comprising said polymorphism are obtained from an isolated cell of the human subject. 
     
     
         7 . A method for detecting a propensity for developing IBD, the method comprising: detecting the presence of a single nucleotide polymorphism on chromosome 21q21 wherein if said single nucleotide polymorphism is present, said patient has an increased risk for developing IBD, wherein said single nucleotide polymorphism is an A at rs28336878 in the PSMG1 gene. 
     
     
         8 . A method as claimed in  claim 7 , wherein the target nucleic acid is amplified prior to detection. 
     
     
         9 . The method of  claim 7 , wherein the step of detecting the presence of said single nucleotide polymorphism further comprises the step of analyzing a polynucleotide sample to determine the presence of said single nucleotide polymorphism by performing a process selected from the group consisting of detection of specific hybridization, measurement of allele size, restriction fragment length polymorphism analysis, allele-specific hybridization analysis, single base primer extension reaction, and sequencing of an amplified polynucleotide. 
     
     
         10 . A method as claimed in  claim 7 , wherein in the target nucleic acid is DNA. 
     
     
         11 . The method of  claim 7 , wherein nucleic acids comprising said polymorphism are obtained from an isolated cell of the human subject. 
     
     
         12 . An isolated nucleic acid comprising a single nucleotide polymorphism associated with an increased risk of developing IBD selected from the group consisting of a T at rs2315008, or an A at RS4809330 in the TNFRSF6B gene and an A at rs2836878 in the PSMG1 gene. 
     
     
         13 . A solid support comprising a nucleic acid comprising the polymorphism of  claim 12 . 
     
     
         14 . A method for identifying agents which modulate aberrant physiological processes associated with IBD, comprising,
 a) providing colonic biopsy samples expressing a single nucleotide polymorphism as claimed in  claim 12 ;   b) providing colonic biopsy samples which express the cognate sequences which lack the polymorphisms of step a);   c) contacting the cells of steps a) and b) with a test agent and   d) analyzing whether said agent alters an aberrant physiological process associated with IBD in samples of step a) relative to those of step b), thereby identifying agents which modulate inflammatory bowel disease.   
     
     
         15 . The method of  claim 14 , wherein said aberrant physiological process associated with IBD is selected from the group consisting of a defect in the colonic mucosal barrier, defects in bacterial clearance and dysregulation of immune responses to commensal intestinal bacteria. 
     
     
         16 . The method as claimed in  claim 2 , wherein the target nucleic acid is amplified prior to detection. 
     
     
         17 . The method as claimed in  claim 2 , wherein the step of detecting the presence of said single nucleotide polymorphism further comprises the step of analyzing a polynucleotide sample to determine the presence of said single nucleotide polymorphism by performing a process selected from the group consisting of detection of specific hybridization, measurement of allele size, restriction fragment length polymorphism analysis, allele-specific hybridization analysis, single base primer extension reaction, and sequencing of an amplified polynucleotide. 
     
     
         18 . A method as claimed in  claim 2 , wherein in the target nucleic acid is DNA. 
     
     
         19 . The method of  claim 2 , wherein nucleic acids comprising said polymorphism are obtained from an isolated cell of the human subject.