10.15 : 유전체 각인과 유전

Genomic imprinting is a phenomenon where the regulation of gene expression is influenced by which parent passed the gene to its offspring.

Somatic cells of many organisms, such as mammals, are diploid, that is they have two copies of the genome- one inherited from the father and one from the mother. Copies of the same gene in somatic cells are known as alleles. 

In most cases, both of the alleles are expressed simultaneously. However, a small number of genes are expressed depending on the source of the inheritance, due to an imprint or mark that accompanies the gene, such as methylation. 

This methylation is resistant to the demethylation that occurs after fertilization and is therefore inherited by the offspring. Methylation of DNA can positively or negatively regulate gene expression. 

In mice, the copy of the insulin-like growth factor-2 gene inherited from the mother is silenced, while the copy from the father is expressed due to imprinting.

A regulatory DNA sequence represses the insulin-like growth factor-2 gene when an insulator protein is bound. For the allele inherited from the mother, the absence of methylation results in the repression of the gene by the insulator protein.

For the allele from the father, methylation at this sequence positively influences the expression of the allele by preventing the protein from binding, resulting in gene expression.

Genomic imprinting can be detrimental to an offspring when the typically expressed allele is mutated.  Unlike most genes, the other allele cannot compensate for the mutation due to silencing by genomic imprinting.  

For example, cyclin dependent kinase inhibitor 1C is a protein-coding gene responsible for the modulation of cell division. Genomic imprinting ensures the expression of only the maternal allele. The maternal allele’s absence or mutation contributes to a condition known as Beckwith–Wiedemann syndrome characterized by a large body size, a large tongue and protrusion of internal organs outside the body through the belly button.