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What is a gene?
A gene is defined as the functional unit of heredity (1). Genes hold genetic information for your entire body and they contain instructions for making proteins. A gene is made up of deoxyribonucleic acid (DNA) that is replicated, translated, and transcripted into specific proteins. The DNA is composed of different sequences of nucleotides (Adenine, Tyrosine, Guanine, and Cytosine) that specifically code for these proteins. This sequence is vital to the formation of proper proteins and errors in the sequence lead to different problems in the body. These errors, or mutations, in the DNA sequence lead to variation in protein formation and can cause major genetic diseases. To name a few, diseases like Cystic Fibrosis, Tay-Sach's Disease, and Sickle-Cell Anemia are caused by mutations in the DNA sequence of their genes. Many diseases, like Crohn's disease, are also linked to specific genetic errors that increase the likelihood of susceptibility to the disease. Investigating genes that cause different diseases gives a greater understanding of how the disease works and how to treat those affected by it.
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PTPN2 Gene
Crohn's disease has been linked to many different genes that increase susceptibility for it. Primarily genes involved in the immune response have been identified as possible risk factors.
One gene, PTPN2, has recently been thought to have a role in Crohn's. This gene is of particular interest because it is involved in mediating immune signaling through phosphorylation in the immune system. People and model organisms with Crohn's often have mutations and differing protein expression of PTPN2.
The PTPN2 gene on chromosome 18 encodes a tyrosine kinase protein that regulates cytokine-induced signaling pathways, epithelial barrier function, and cytokine secretion in the intestinal cells [2].
Disturbance in the PTPN2 gene causes impaired autophagosome formation, which leads to disruption of the immune system and contributes to the development of Crohn’s disease [3].
Studies identifying risk genes in people with Crohn's have found a significant link to PTPN2. The most notable research has been performed with mouse models of the disease where Crohn's phenotypes (like diarrhea and bloody stool) were observed in the mice after gene knockout of PTPN2(mouse model study). The mouse experiment demonstrates how dysfunction of PTPN2 leads to Crohn's disease, which makes PTPN2 a very vital piece to the puzzle of Crohn's disease.
One gene, PTPN2, has recently been thought to have a role in Crohn's. This gene is of particular interest because it is involved in mediating immune signaling through phosphorylation in the immune system. People and model organisms with Crohn's often have mutations and differing protein expression of PTPN2.
The PTPN2 gene on chromosome 18 encodes a tyrosine kinase protein that regulates cytokine-induced signaling pathways, epithelial barrier function, and cytokine secretion in the intestinal cells [2].
Disturbance in the PTPN2 gene causes impaired autophagosome formation, which leads to disruption of the immune system and contributes to the development of Crohn’s disease [3].
Studies identifying risk genes in people with Crohn's have found a significant link to PTPN2. The most notable research has been performed with mouse models of the disease where Crohn's phenotypes (like diarrhea and bloody stool) were observed in the mice after gene knockout of PTPN2(mouse model study). The mouse experiment demonstrates how dysfunction of PTPN2 leads to Crohn's disease, which makes PTPN2 a very vital piece to the puzzle of Crohn's disease.
PTPN2 Mutation
Variants in PTPN2 are linked to Crohn's disease susceptibility. There are two major causal variants of PTPN2 that are characterized by SNPs. The first variant, rs2542151 is located 5.5 kilobase-pairs downstream of the 3' tail of the transcript and is known to have the strongest link with the disease state. The second variant is rs1893217 and is located in the same region of the genome. These two polymorphism variants within PTPN2 are both located in the intronic region of the DNA and are believed to be involved in the alternative splicing that leads to variation in expression of the isoforms of PTPN2. (4)
The varying expression in isoforms levels cause complications in Crohn's disease. This means that the SNP variations in PTPN2 that cause the varying expression in isoform levels are directly leading to a disease state. (5)
The varying expression in isoforms levels cause complications in Crohn's disease. This means that the SNP variations in PTPN2 that cause the varying expression in isoform levels are directly leading to a disease state. (5)
References
- http://ghr.nlm.nih.gov/handbook/basics/gene
- Glas J, Wagner J, Seiderer J, et al. PTPN2 gene variants are associated with susceptibility to both Crohn’s disease and ulcerative colitis supporting a common genetic disease background. PLoS One 2012;7:3.
- Scharl M, Rogler G. The role for protein tyrosine phosphatase nonreceptor type 2 in regulating autophagosome formation. Ann N Y Acad Sci 2012; 1257: 93-102.
- Marcil V, Mack DR, Kumar V, et. al. Association between the PTPN2 gene and Crohn's disease: dissection of potential causal variants. 2013. Inflamm. Bowel Dis. (6):1149-55.
- Bussieéres-Marmen, Hutchins, Schirbel, et. al. Characterization of PTPN2 and its use as a biomarker. Science Direct 2014. V. 65 (2) p 239-246.
Specifications of PTPN2:
Accession #: NM_002828.3
Chromosome 18
FASTA
Accession #: NM_002828.3
Chromosome 18
FASTA