Genomic imprinting is an exception to standard inheritance. While most genes are equally active from both parents, imprinting is an epigenetic process where gene expression is determined by its parental origin. This results in monoallelic expression, where only one of two inherited gene copies is active. Maternal imprinting is a specific form where the allele from the mother is silenced, leaving only the paternal allele to be expressed. This parent-of-origin effect is necessary for interpreting inheritance patterns in family health histories.
The Mechanism of Maternal Imprinting
The silencing of the maternal allele is an epigenetic event, meaning it modifies DNA accessibility without changing the sequence itself. This process begins during the development of female germ cells (eggs), where specific genes are tagged as maternal through DNA methylation. In this process, methyl groups are attached to specific parts of the DNA, acting as a signal to silence the gene.
These epigenetic marks are established in the egg and maintained in the embryo’s cells after fertilization. The methylation pattern ensures only the paternal copy will be active for these genes. This is achieved by enzymes that create a condensed DNA structure that the cell’s machinery cannot read.
This silencing is not permanent; it is reset and re-established in the germline of each generation. When an individual forms their own sperm or eggs, their parents’ imprints are erased. New imprints are then established based on the individual’s sex, setting a paternal pattern in sperm and a maternal pattern in eggs.
Interpreting a Maternal Imprinting Pedigree
In a maternally imprinted disorder, the disease only appears when the normally active paternal allele is faulty or absent. A healthy maternal allele cannot compensate because it is silenced, creating a predictable inheritance pattern in a pedigree.
An individual is only affected if they inherit the defective allele from their father. If the same defective allele comes from the mother, it is silenced, and the person will be an unaffected carrier of the mutation.
An affected male, who has a faulty paternal allele, will pass this allele to all of his children. Because the allele retains its paternal origin in his offspring, their own maternal allele cannot compensate. As a result, all of his children will be affected, a clear sign of this inheritance mode.
Conversely, the pattern for an affected female is different. She will pass the defective allele to half of her children. However, for her offspring, this allele is now of maternal origin. Because the maternal allele is silenced for this gene, her children will be phenotypically normal, though they are carriers of the faulty gene.
Distinguishing from Other Inheritance Patterns
The pattern of maternal imprinting can be confused with other inheritance modes, but there are clear differences. In paternal imprinting, the paternal allele is silenced, and a disorder arises when the active maternal allele is defective. This results in a mirror-image pedigree where affected females can pass the condition on, but affected males cannot.
Autosomal dominant inheritance can appear similar, but the rules are different. In these conditions, an affected individual has a 50% chance of passing the trait to each child, regardless of the parent’s or child’s sex. The trait also appears in every generation, and both males and females can transmit the condition to their sons and daughters.
Mitochondrial inheritance shows a strong maternal linkage. Mitochondrial DNA is inherited almost exclusively from the mother, so an affected mother passes a mitochondrial condition to all her offspring. An affected father will not pass the condition to any of his children, which differs from maternal imprinting where an affected female’s children are unaffected carriers.
Clinical Examples and Significance
Angelman syndrome is an example of a disorder caused by maternal imprinting, arising from the loss of function of the UBE3A gene on chromosome 15. In the brain, the maternal copy of UBE3A is silenced, so individuals rely on the paternal copy. If the paternal copy is deleted or mutated, the person has no functional UBE3A in their brain, leading to the developmental delays and neurological features of the syndrome.
The same region of chromosome 15 is involved in Prader-Willi syndrome, but it demonstrates paternal imprinting. Here, genes on the paternal chromosome are silenced, and the individual relies on the active maternal copies. If the maternal copies are faulty, Prader-Willi syndrome develops.
Understanding these patterns through pedigree analysis is important in genetic counseling. It allows counselors to provide families with accurate risk assessments for future offspring. For families with a history of such conditions, analyzing the pedigree helps determine who may be a carrier and the risks of passing the condition on. This information helps families make informed decisions about reproductive planning.