Human Genetics: What is Genetic Imprinting?

Genetic or genomic imprinting is a mechanism by which gene expression depends on parental origin. The process does not follow the classical Mendelian inheritance rules.

A gene comes in two versions (alleles), one from your mum and one from your dad. Usually both of these are expressed. However, in genomic imprinting only one of these is expressed and it may be the gene inherited from your father or your mother. Of the 25,000-30,000 genes in the human body it's been estimated that fewer than 1% are imprinted genes. In mammals they have been found to play a role in embryonic development, but also in the development of genetic abnormalities.

Perhaps the best way to understand genetic imprinting, its causes, and its consequences is to look at two excellent examples: Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS).

According to the PWS web site, the expression of the gene or genes (known as q11-13) located on chromosome 15 are implicated in PWS. Although not fully understood, PWS is the result of one copy of such gene (or genes) being silenced due to genomic imprinting. Normally, a person will receive copies of the same gene (alleles) from both father and mother. In PWS, the copy inherited from the father is silenced due to a genomic imprinting process. On the contrary in Angelman Syndrome (AS), the copy inherited from the mother is lost. The “silencing” of either the father’s copy of the gene or the mother’s allele (due to genetic imprinting) results in two very different and distinct genetic disorders. PWS leads to obesity, short stature and extremities, and moderate mental retardation, while AS leads to a different situation: hyperactivity, jerky movements, laughter outbursts, and severe mental retardation.

Genetic imprinting was discovered very recently in 1984. Despite the fact that much research has been devoted to genetic imprinting the whole process is still not completely understood - why and how is one gene marked for expression over the other?

Ariel et al. (1995) used advanced biotech techniques to study the extent of methylation on the noncoding RNA gene called Xist in early mice embryos. Their results showed that methylation of the Xist gene was an important part of the X-imprinting process. More recently, Ng et al. (2007), found that noncoding RNA plays a role in random imprinting of the X chromosome.

Ariel, M et al. (1995) Gamete-specific methylation correlates with imprinting of the murine Xist gene. Nature Genetics 9, 312

Jurg Ott. 1999. Analysis of human genetic linkage. JHU Press.

Ng, K. et al. 2007. Xist and the order of silencing. EMBO Reports 8, 34