Genomic Imprinting and Parent-of-Origin Effects

For a small set of genes it matters which parent an allele came from: imprinting silences one parental copy through epigenetic marks, so that inheritance can violate the usual symmetry of Mendelian transmission.

Definition

Genomic imprinting is an epigenetic process in which certain genes are expressed from only one parental allele according to whether it was inherited from the mother or the father, producing parent-of-origin effects on phenotype.

Scope

This topic covers the phenomenon of genomic imprinting, the epigenetic marking of alleles in the germline according to parental origin, the resulting monoallelic, parent-specific expression of imprinted genes, the resetting of imprints between generations, and the classic imprinting disorders that arise when the marks or the chromosomes carrying them are disturbed. It treats parent-of-origin effects as a special case of epigenetic regulation; the general chromatin mechanisms are covered in the adjacent topic.

Core questions

• How are imprints established in the germline and reset between generations?
• Why does the parent of origin of an allele determine whether it is expressed?
• How do imprinting errors and uniparental disomy cause disease?
• Why might imprinting have evolved despite the redundancy it sacrifices?

Key concepts

• Genomic imprinting and monoallelic expression
• Germline establishment and resetting of imprints
• Imprinting control regions
• Uniparental disomy
• Imprinting disorders

Mechanisms

During gametogenesis, differential DNA methylation is laid down at imprinting control regions according to parental sex, so the maternal and paternal copies of an imprinted gene carry distinct marks; these silence one allele in the offspring, and because the marks are erased and re-established each generation, expression depends on the most recent parental origin rather than the DNA sequence.

Clinical relevance

Imprinting explains why deletions of the same chromosomal region cause Prader-Willi syndrome when paternally inherited and Angelman syndrome when maternally inherited, and why uniparental disomy can produce disease; recognizing parent-of-origin patterns is important in genetic diagnosis and counseling.

History

Nuclear-transfer experiments in mice in the mid-1980s showed that maternal and paternal genomes are not equivalent, establishing imprinting; the first imprinted genes were identified around 1991, and Haig's parental-conflict hypothesis offered an evolutionary rationale for why imprinting arose.

Debates

Why imprinting evolved

The leading parental-conflict hypothesis holds that imprinting reflects a tug-of-war between paternal alleles favouring greater resource extraction by offspring and maternal alleles restraining it, but alternative explanations exist and the question remains open.

Key figures

• Azim Surani
• Davor Solter
• David Haig

Seminal works

• allis2007

Frequently asked questions

What does parent-of-origin effect mean?

It means the phenotype produced by an allele depends on whether it was inherited from the mother or the father; for imprinted genes one parental copy is epigenetically silenced, so only the copy from the other parent is expressed.

How can the same deletion cause two different syndromes?

If a chromosomal region contains imprinted genes, losing it from the paternal chromosome removes the only active copies of paternally expressed genes, while losing it from the maternal chromosome removes maternally expressed ones, producing distinct disorders such as Prader-Willi and Angelman syndromes.