The paternal allele of Igf2 (insulin-like growth factor 2) is expressed, while the maternal allele is silenced. If a child inherits a deletion of Igf2 from their father, what is the expected growth phenotype?
ANormal growth, because the maternal allele compensates
BGrowth restriction, because the only active copy (paternal) is deleted, and the intact maternal copy is silenced by imprinting and cannot compensate
COvergrowth, because loss of Igf2 removes growth inhibition
DNo effect, because Igf2 is not important for growth
This is the key clinical consequence of imprinting: for imprinted genes, cells are functionally hemizygous — they rely on only one allele. The maternal Igf2 allele is present but epigenetically silenced (methylated), so it cannot compensate for loss of the paternal copy. A paternal deletion effectively eliminates Igf2 expression entirely, causing growth restriction. Conversely, inheriting the same deletion from the mother would have no effect (the maternal allele is already silent). This parent-of-origin-dependent inheritance pattern is the diagnostic hallmark of imprinting disorders.
Question 2 True / False
Genomic imprinting is caused by differences in DNA sequence between the maternal and paternal alleles.
TTrue
FFalse
Answer: False
Imprinting is epigenetic, not genetic — the DNA sequence of the maternal and paternal alleles is identical. The difference is in the DNA methylation pattern, established during gametogenesis. In sperm, certain imprinting control regions are methylated; in eggs, different regions are methylated. After fertilization, these differential methylation marks are maintained through DNA replication by maintenance methyltransferase (DNMT1), ensuring that the parental identity of each allele is preserved. The imprinting marks are erased in primordial germ cells and re-established according to the sex of the developing individual, resetting the cycle each generation.
Question 3 Short Answer
Explain why deletion of the same chromosomal region (15q11-q13) causes Prader-Willi syndrome when inherited from the father but Angelman syndrome when inherited from the mother.
Think about your answer, then reveal below.
Model answer: The 15q11-q13 region contains both paternally expressed genes (whose loss causes Prader-Willi syndrome — obesity, intellectual disability, hypotonia) and maternally expressed genes (specifically UBE3A, whose loss causes Angelman syndrome — severe intellectual disability, seizures, happy demeanor). When the paternal copy is deleted, the paternally expressed genes are lost and the (silenced) maternal copies cannot compensate — causing Prader-Willi. When the maternal copy is deleted, the maternally expressed UBE3A gene is lost and the (silenced) paternal copy cannot compensate — causing Angelman. The same deletion produces different syndromes depending on parent of origin because different genes in the region are active on each parental chromosome.
These reciprocal syndromes from the same deletion were key evidence for genomic imprinting in humans. They also demonstrate a practical clinical concern: genetic counseling for imprinting disorders must account for which parent carries the mutation, not just whether the mutation is present.