Genomic imprinting: implications for human disease

Abstract

Genomic imprinting refers to an epigenetic marking of genes that results in monoallelic expression. This parent-of-origin dependent phenomenon is a notable exception to the laws of Mendelian genetics. Imprinted genes are intricately involved in fetal and behavioral development. Consequently, abnormal expression of these genes results in numerous human genetic disorders including carcinogenesis. This paper reviews genomic imprinting and its role in human disease. Additional information about imprinted genes can be found on the Genomic Imprinting Website at http://www.geneimprint.com.

Figure 1.

Imprint establishment and propagation during gametogenesis and development. The paternal allele (dashed line) is imprinted and the maternal allele is expressed (solid line). The “imprint mark” (black box) represents a parental-specific methylation established during gametogenesis. A: The maternal and paternal genomes have different imprint patterns following fertilization. B: Both “imprint marks” and imprint reading are maintained during somatic cell division. C: The parental specific imprints are erased in the primordial germ cells. D: The appropriate “imprint marks” are reestablished for the next generation.

Figure 2.

Total number of papers published on genomic imprinting versus time.

Figure 3.

A: Only one allele of a tumor suppressor gene (T) is expressed because of genomic imprinting (T^X). Loss of heterozygosity (LOH) of the expressed allele or an inactivating mutation in the expressed allele (T^M) results in loss of tumor suppressor function. B: Only one allele of the proto-oncogene (P) is expressed because of genomic imprinting (P^X). Loss of imprinting (LOI) or uniparental disomy (UPD) results in biallelic expression of the proto-oncogene.