duplication. TEs use a number of different mechanisms to cause genetic instability and disease in their host genomes. Expression of disease-causing, damaging proteins that inhibit normal cellular function. Many TEs contain promoters which drive transcription of their own transposase. These promoters can cause aberrant expression of linked genes, causing disease or mutant phenotypes. Diseases Diseases often caused by TEs include Hemophilia A and B LINE1 (L1) TEs that land on the human Factor VIII have been shown to cause haemophilia Severe combined immunodeficiency Insertion of L1 into the APC gene causes colon cancer, confirming that TEs play an important role in disease development. Porphyria Insertion of Alu element into the PBGD gene leads to interference with the coding region and leads to acute intermittent porphyria (AIP). Predisposition to cancer LINE1(L1) TE's and other retrotransposons have been linked to cancer because they cause genomic instability. Duchenne muscular dystrophy. Caused by SVA transposable element insertion in the fukutin (FKTN) gene which renders the gene inactive. Alzheimer's Disease and other Tauopathies Transposable element dysregulation can cause neuronal death, leading to neurodegenerative disorders Rate of transposition, induction and defense One study estimated the rate of transposition of a particular retrotransposon, the Ty1 element in Saccharomyces cerevisiae. Using several assumptions, the rate of successful transposition event per single Ty1 element came out to be about once every few months to once every few years. Some TEs contain heat-shock like promoters and their rate of transposition increases if the cell is subjected to stress, thus increasing the mutation rate under these conditions, which might be beneficial to the cell. Cells defend against the proliferation of TEs in a number of ways. These include piRNAs and siRNAs, which silence TEs after they have been transcribed. If organisms are mostly composed of TEs, one might assume that disease caused by misplaced TEs is very common, but in most cases TEs are silenced through epigenetic mechanisms like DNA methylation, chromatin remodeling and piRNA, such that little to no phenotypic effects nor movements of TEs occur as in some wild-type plant TEs. Certain mutated plants have been found to have defects in methylation-related enzymes (methyl transferase) which cause the transcription of TEs, thus affecting the phenotype. One hypothesis suggests that only approximately 100 LINE1 related sequences are active, despite their sequences making up 17% of the human genome. In human cells, silencing of LINE1 sequences is triggered by an RNA