Table 1. Some human diseases linked to LINE and SINE insertions.

The extensive role of LINEs and SINEs in the regulation of human gene expression suggests that they contribute to disease in as yet undiscovered ways.

Effect of LINE or SINE insertionPossible mechanism(s) of pathogenesisExamples of associated diseasesReference
Genomic deletions and rearrangementsLINE/SINE-mediated homologous recombination: DNA sequence loss; genomic instabilityProstate cancer, pyruvate dehydrogenase complex deficiency, leukemia, Alport syndrome, breast cancer (83)
Hereditary nonpolyposis colorectal cancer, Von Hippel–Lindau disease (86)
Disruption of protein‐coding sequencesAberrant protein production; nonsense‐mediated mRNA decay (NMD)Hemophilia B, breast cancer, colon cancer, neurofibromatosis type 1 (83)
Altered DNA methylationIncreased expression of LINE and SINE RNAEarly event in many cancers (86)
Altered pre‐mRNA splicingAberrant protein production; NMDFukuyama-type congenital muscular dystrophy, neurofibromatosis type 1, hemophilia A (83)
Neurofibromatosis type 1, hemophilia A, breast cancer, Coffin‐Lowry syndrome (84)
Altered 3′-end formationPremature transcription termination; altered protein production; NMD; altered mRNA stability, localization, or translatabilityX‐linked retinitis pigmentosa (83)
Altered mRNA stabilityReduced protein production; altered temporal and/or spatial gene expressionX-linked dilated cardiomyopathy (83)
Hemophilia A, hereditary nonpolyposis colorectal cancer, hyper–immunoglobulin M syndrome (84)
Sites of A-to‐I editingLoss of ADAR editing of target sites, possibly at Alu elementsAmyotrophic lateral sclerosis (ALS), astrocytoma, metastatic melanoma, Aicardi-Goutières syndrome, hepatocellular carcinoma (100)