Genetic Imprinting
Some genes are expressed only from the maternal chromosome, while others genes are expressed only from the paternal chromosome. The second gene copy is silenced during gamete formation in the egg (when maternal gene copies are silenced) or the sperm (when paternal gene copies are silenced). This is known as genetic imprinting. Imprinting occurs in each generation when new egg and sperm cells are produced.
Relatively few genes in humans are known to be imprinted and such genes tend to be clustered in the genome. The gene imprinting occurs by the addition of methyl groups to the DNA of the silenced gene, preventing transcription of the gene. This gene silencing acts in much the same manner as mutation or deletion of one copy of a gene, except that it is not a permanent, heritable change. If the one remaining active gene is deleted or mutated, there is no extra, functional copy on the second chromosome; therefore, mutation of the single, active copy of an imprinted gene may result in disease. Similarly, as a result of an error, cells may receive all or part of a pair of chromosomes from a single parent. For imprinted genes, that means that the cell receives either two imprinted copies or two active copies. If both copies are imprinted, there is no functional gene. Two active copies of a gene may also result from a mutation that leads to loss of imprinting; neither copy will be silenced. Too many active copies of a gene may result in overexpression of a gene, which can cause disease. A number of cancers have been associated with failure to imprint genes, especially genes that produce growth factors. Overexpression of growth factors can disrupt the cell cycle, contributing to uncontrolled cell growth and cancer. (See the Cell Biology and Cancer unit.)
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