Mutations in the IL2RG gene cause approximately 30 percent of severe combined immunodeficiency disorder (SCID) cases in humans. These mutations result in alterations to a protein component of cytokine receptors that are essential for proper development of the immune system. The IL2RG gene is composed of eight exons and contains upstream and downstream sequences that are necessary for proper transcription and translation. Below are some of the mutations observed. For each, explain its likely influence on the IL2RG gene product (assume its length to be 375 amino acids).
Large deletion covering Exons 2 and 3

Verified step by step guidance

1. Step 1: Understand the structure of the IL2RG gene and its product. The gene has 8 exons, and the full-length protein is 375 amino acids long, meaning each exon contributes a portion of the coding sequence.
2. Step 2: Recognize that a large deletion covering Exons 2 and 3 removes the coding information contained in these two exons. This will lead to a loss of the amino acid sequence normally encoded by these exons.
3. Step 3: Consider the effect of this deletion on the reading frame. Since exons are spliced together during mRNA processing, removing two entire exons may cause a frameshift mutation if the total number of nucleotides deleted is not a multiple of three, potentially altering downstream amino acids and introducing a premature stop codon.
4. Step 4: Predict the impact on the protein product. The deletion likely results in a truncated or nonfunctional protein due to missing critical domains encoded by Exons 2 and 3 or due to nonsense-mediated decay if a premature stop codon is introduced.
5. Step 5: Conclude that this mutation would severely disrupt the IL2RG protein function, impairing cytokine receptor formation and leading to the immunodeficiency phenotype observed in SCID.

Key Concepts

Gene Structure and Exons

Genes are composed of exons and introns; exons contain the coding sequences that are spliced together to form mRNA. Deletions of exons remove essential coding regions, potentially leading to truncated or nonfunctional proteins. Understanding exon organization helps predict how mutations affect the final protein product.

Impact of Deletions on Protein Function

Large deletions that remove multiple exons can cause frameshifts or loss of critical protein domains, often resulting in nonfunctional or unstable proteins. Such deletions may disrupt the reading frame or eliminate essential regions, impairing the protein’s role in cellular processes.

Role of IL2RG in Immune System Development

The IL2RG gene encodes a common gamma chain shared by several cytokine receptors vital for immune cell development. Mutations in IL2RG disrupt cytokine signaling, leading to severe combined immunodeficiency (SCID) by impairing lymphocyte maturation and function.