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. Identify the genotype of each family member, using the sizes of mRNAs to indicate each allele. (For example, a person who is homozygous wild type is indicated as '1250/1250.')

Verified step by step guidance

1. Understand the problem: The disease is inherited as an autosomal recessive trait, meaning that individuals with two copies of the mutant allele (homozygous recessive) will have the disease. The wild-type allele produces a mature mRNA of 1250 nucleotides, and the sizes of the exons are provided. Northern blot analysis will reveal the sizes of mRNAs produced by each allele in each family member.
2. Analyze the northern blot results: Examine the sizes of the mRNAs detected for each family member. If a person is homozygous wild type, their mRNA will be 1250 nt. If a person is homozygous for the mutant allele, their mRNA will likely differ in size due to a mutation affecting splicing or exon inclusion. Heterozygous individuals will show two bands corresponding to the wild-type and mutant mRNAs.
3. Determine the genotype of the parents: Since the parents have both healthy and affected children, they must each be heterozygous (carriers) for the mutant allele. This means their genotypes are '1250/mutant_size,' where 'mutant_size' corresponds to the size of the mutant mRNA observed in the northern blot.
4. Determine the genotype of the healthy children: Healthy children must have at least one wild-type allele. If they are homozygous wild type, their genotype will be '1250/1250.' If they are heterozygous, their genotype will be '1250/mutant_size.' Use the northern blot results to confirm which bands are present for each child.
5. Determine the genotype of the affected children: Affected children must be homozygous for the mutant allele, meaning their genotype will be 'mutant_size/mutant_size.' Use the northern blot results to confirm the size of the mutant mRNA and verify that only this size is present for the affected children.

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 trait or disease. Carriers, who possess one normal and one mutated allele, do not show symptoms but can pass the mutated allele to their offspring. This concept is crucial for understanding how the disease manifests in the family described, as both parents can be carriers without being affected.

Mature mRNA and Exons

Mature mRNA is the final form of messenger RNA that has undergone processing, including splicing, where introns are removed and exons are joined together. The lengths of the exons contribute to the total length of the mature mRNA, which in this case is 1250 nucleotides. Understanding the structure of mRNA and the significance of exons is essential for analyzing the northern blot results and determining the genotypes of the family members based on the presence or absence of specific mRNA sizes.

Northern Blot Analysis

Northern blot analysis is a technique used to detect specific RNA sequences in a sample. It involves the separation of RNA by gel electrophoresis, transfer to a membrane, and hybridization with labeled probes. This method allows researchers to visualize the expression levels of different mRNA transcripts, which is critical for identifying the genotypes of the family members based on the sizes of the mRNAs present in the northern blot results.