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).
Insertion in Exon 1, causing frameshift

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).

Deletion in Exon 2, causing frameshift

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).

Insertion in Exon 7, causing frameshift

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).

Nonsense mutation in a coding region

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).

Missense mutation

It has been noted that most transposons in humans and other organisms are located in noncoding regions of the genome—regions such as introns, pseudogenes, and stretches of particular types of repetitive DNA. There are several ways to interpret this observation. Describe two possible interpretations. Which interpretation do you favor? Why?

Skin cancer carries a lifetime risk nearly equal to that of all other cancers combined. Following is a graph [modified from K. H. Kraemer (1997). Proc. Natl. Acad. Sci. (USA) 94:11 14] depicting the age of onset of skin cancers in patients with or without XP, where the cumulative percentage of skin cancer is plotted against age. The non-XP curve is based on 29,757 cancers surveyed by the National Cancer Institute, and the curve representing those with XP is based on 63 skin cancers from the Xeroderma Pigmentosum Registry.

Explain why individuals with XP show such an early age of onset.