基因组印记和遗传

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.

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.

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.

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.

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.

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.

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.