A hereditary disease is inherited as an autosomal recessive trait1. The wild-type allele of the disease gene produces a mature mRNA that is 1250 nucleotides (nt) long. Molecular analysis shows that the mature mRNA consists of four exons that measure 400 nt (exon 1), 320 nt (exon 2), 230 nt (exon 3), and 300 nt (exon 4). A mother and father with two healthy children and two children with the disease have northern blot analysis performed in a medical genetics laboratory. The results of the northern blot for each family member are shown here. Based on your analysis, what is the most likely molecular abnormality causing the disease allele?

Key Concepts

Autosomal Recessive Inheritance

Autosomal recessive inheritance refers to a pattern where two copies of a mutated gene, one from each parent, are necessary for an individual to express a hereditary disease. In this case, both parents can be carriers of the mutation without showing symptoms, which is why they have healthy children alongside affected ones. Understanding this concept is crucial for analyzing the inheritance pattern in the family described.

Mature mRNA Structure

Mature mRNA is the final product of gene expression, consisting of exons that have been spliced together after introns are removed. The total length of the mature mRNA is determined by the sum of the lengths of its exons. In this scenario, the mature mRNA is 1250 nucleotides long, and the specific lengths of the four exons provide insight into potential mutations that could affect mRNA processing or stability, leading to the disease.

Northern Blot Analysis

Northern blot analysis is a technique used to detect specific RNA sequences in a sample. It allows researchers to assess the expression levels of genes and identify any abnormalities in mRNA size or abundance. In the context of this question, the northern blot results for the family members can reveal whether the disease allele produces a defective mRNA, which is essential for determining the molecular basis of the hereditary disease.