Question

A mutation in the SYN3 intron is associated with macular degeneration. Based on population genetics principles, speculate about how a mutation in an intron in the human genome can be associated with a phenotype.

Answer 1

• Genes regulated by introns are often expressed in most tissues and are among the most highly expressed in the genome.

• Though gene regulation by general and regulatory transcription factors binding to conserved DNA sequences in promotors explains the behavior of most genes, the prominent effect can be by mutations in introns.

• Certain introns may be the primary element directing the expression of some of the most highly expressed genes in the genome, causing the gene to express any phenotypical change.

• It is assumed that larger genes with long introns were more prone to splicing defects resulting in mutations, the cause for disorders in both phenotype and genotype.

• If there is an intronic alteration occurring at regulatory regions it can affect gene expression levels which results in the cause of many abnormalities in phenotypic character.

• Deep intronic mutations can disrupt transcription regulatory motifs and non-coding RNA genes, which are a great cause of monogenic disorders as well as hereditary cancer syndromes.