10.15
Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both al…
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.
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Q1: What is genomic imprinting and how does it affect gene expression?
Genomic imprinting is a phenomenon where gene expression depends on which parent passed the gene to offspring. Chemical tags, such as methyl groups, mark DNA in the copy inherited from one parent. These tags are resistant to removal after fertilization and persist through inheritance, resulting in selective expression of only the paternal or maternal allele while the other remains silenced.
Q2: How does methylation regulate imprinted genes in mammals?
Methylation can positively or negatively regulate imprinted gene expression. In the insulin-like growth factor-2 gene, methylation on the paternal allele prevents an insulator protein from binding, allowing gene expression. On the maternal allele, the absence of methylation permits the insulator protein to bind and repress the gene, ensuring only the paternal copy is expressed.
Q3: Why are mutations in imprinted genes particularly harmful to organisms?
Mutations in imprinted genes are detrimental because the silenced allele cannot compensate for defects in the expressed allele, unlike most genes. For example, cyclin dependent kinase inhibitor 1C is expressed only from the maternal allele. If this allele is absent or mutated, no functional protein is produced, leading to genetic disorders such as Beckwith-Wiedemann syndrome.
Q4: What is uniparental disomy and how does it relate to genomic imprinting disorders?
Uniparental disomy occurs when two copies of a gene are inherited from the same parent instead of one from each. Maternal uniparental disomy means two maternal copies are present; paternal uniparental disomy means two paternal copies exist. If both inherited copies are silenced alleles, genetic disorders result because no functional gene product is available.
Q5: What are the characteristics of Prader-Willi syndrome and its genetic cause?
Prader-Willi syndrome occurs due to maternal uniparental disomy on chromosome 15, where two maternal gene copies are inherited and the paternal copy is absent. Affected individuals display obesity, sexual underdevelopment, and mental disabilities. The condition arises because imprinting silences the maternal allele, leaving no functional paternal gene to compensate.
Q6: How does Angelman syndrome differ from Prader-Willi syndrome in terms of inheritance?
Angelman syndrome is associated with paternal uniparental disomy on chromosome 15, opposite to Prader-Willi syndrome. People with Angelman syndrome may show mental disabilities, developmental deficiencies, sleep disorders, and hyperactivity. Both syndromes involve chromosome 15 but differ in which parent's genes are duplicated and which imprinted alleles remain silenced.
Q7: How do alleles normally function in diploid organisms compared to imprinted genes?
In most diploid organisms, both alleles are expressed simultaneously, allowing one allele to compensate if the other is mutated or absent. However, imprinted genes break this pattern through regulation of expression during transcription and translation. Only one parent's allele is expressed while the other is silenced, preventing compensation and making imprinted genes vulnerable to single mutations.