Mutations: somatic

Mitochondrial DNA is also prone to noninherited (somatic) mutations. Somatic mutations occur in the DNA of certain cells during a person s lifetime, and typically are not passed to future generations. Because mitochondrial DNA has a limited ability to repair itself when it is damaged, these mutations tend to build up over time. A buildup of somatic mutations in mitochondrial DNA has been associated with some forms of cancer and an increased risk of certain age-related disorders such as heart disease, Alzheimer disease, and Parkinson disease. Additionally, research suggests that the progressive accumulation of these mutations over a person s lifetime may play a role in the normal process of aging. 

Gene therapy is used to correct the effects of a disease-causing mutation. Somatic cell gene therapy is used in humans because the alteration is not transmitted to offspring. Germline gene therapy (not practiced in humans) alters all cells in the body and results in transmission of the alteration to offspring. 

No somatic mutation Somatic mutation of other parts of V possible... 

Wilson (140) suggests a number of mechanisms of teratogenesis including 1. mutations (somatic, that is non-heritable) 2. 

A mutagen is a chemical that can induce alterations in the DNA. Mutations occurring in germ cells are inheritable and may lead to genetic diseases. If mutations take place in somatic cells, carcinogenesis may be initiated. 

Organ specific autoimmune disease Constitutively activating somatic mutation in TSH... 

Greenman C, Stephens P, Smith R, et al (2007) Patterns of somatic mutation in human cancer genomes. Nature 446 153-158... 

D. melanogaster/6 e afy exposure Recessive lethal somatic mutation + Tripathy et al. 1987... 

Somatic hypermutation High frequency of mutation that occurs in the gene segments encoding the variable regions of antibodies during the differentiation of B lymphocytes into antibody-producing plasma cells. 

Figure 6. The c-mos negative regulatory element (NRE). Nucleotide positions of the NRE are shown relative to the spermatocyte transcription start site, taken as 280 base pairs upstream of the c-mos ATG (see Fig. 4). The endpoints of the NRE are defined by deletions that allow c-mos expression in NIH 3T3 and other somatic cells. Mutations of the sequences designated by boxes 1,2, and 3 also allow c-mos transcription in NIH 3T3 cells, indicating that these sequences represent functional elements within the NRE. Boxes 1 and 2 are similar to sequences upstream of the protamine (Prot) promoter that inhibit in vitro transcription in HeLa cell extracts. A sequence just upstream of box 2 is also similar to a putative repressor-binding site in the regulatory region of Pgk2.

Lavoie, T. B., Drohan, W. N. and Smith-Gill, S. J. (1992), Experimental analysis by site-directed mutagenesis of somatic mutation effects on affinity and fine specificity in antibodies specific for lysozyme , f. Immunol., 148, 503-513. 

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