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Molecular Basis of Heredity: Part 2. Genomes

Author(s): Raye L. Alford, PhD

Regulation of the Human Genome (II)

Methylation is another mechanism of gene regulation. In methylation, portions of the DNA molecule, particularly regions of the DNA that control transcription are chemically modified through the action of enzymes called DNA methyltransferases. DNA methyltransferases attach a methyl group (CH3) to the 5th position carbon of cytosine bases, typically when cytosines occur in the context of C-G dinucleotides, sometimes referred to as CpG islands. Methylation of DNA usually results in the silencing or suppression of gene expression. Alternatively, a lack of methylation is usually associated with an active state of gene expression. Methylation is crucial for the regulation of gene expression and control of cellular growth throughout life, from embryonic development to adulthood. Methylation also is crucial for X-chromosome inactivation and imprinting.

Imprinting is a form of gene silencing whereby individual genes or groups of genes are methylated during gametogenesis to impart parent of origin effects on gene expression. For example, if a gene is maternally imprinted, (that is silenced in the maternal copy during female gametogenesis) only the paternal copy of the gene is expressed in the child. Paternal imprinting of genes also occurs. During gametogenesis, parental imprints are erased and reset in a manner consistent with whether the gametogenesis is occurring in a male or a female. A number of human genetic diseases occur because of mutations in imprinted genes or in the genetic control sequences responsible for setting, resetting or controlling imprinted regions. Such diseases include Angelman syndrome and Prader-Willi syndrome, which occur because of mutations in imprinted genes or errors in imprinting of genes on chromosome 15. These disorders also can be caused when errors in mitosis or meiosis produce a child who inherits both copies of his or her chromosome 15 from a single parent, resulting in inheritance of only imprinted copies of the genes involved and no active copy. This phenomenon is called uniparental disomy, or UPD.