RAS question
Mutations in which gene, identified by Brunkow and Ramsdell, cause IPEX syndrome in humans?
Correct answer: (A) Foxp3.
Mutations in FOXP3, the human counterpart of the Foxp3 gene identified by Mary Brunkow and Fred Ramsdell in scurfy mice, cause IPEX syndrome in humans.
Explanation
In 2001, Mary Brunkow and Fred Ramsdell traced the severe autoimmune phenotype of scurfy mice to Foxp3, a forkhead box gene on the X chromosome. Their work did not stop at naming the mouse gene: they showed that a normal Foxp3 copy could rescue male scurfy mice from disease. They then connected this mouse finding to human disease, demonstrating with collaborators that mutations in FOXP3, the human counterpart of the scurfy mouse gene, were responsible for IPEX syndrome. Foxp3/FOXP3 controls regulatory T-cell tolerance and autoimmune disease, unlike general cancer or cystic fibrosis genes.
Why the other options are wrong
- (B) BRCA1 is a breast and ovarian cancer susceptibility gene, not the Brunkow-Ramsdell scurfy-mouse gene responsible for IPEX.
- (C) TP53 is a tumor-suppressor gene involved in cell-cycle control and cancer, not the Foxp3 gene whose mutations are responsible for IPEX syndrome.
- (D) CFTR causes cystic fibrosis through chloride-channel defects, not the Brunkow-Ramsdell Foxp3-linked autoimmune disorder IPEX.
Concept
Immune regulation in Science and Technology includes single-gene control of regulatory T-cell tolerance and autoimmune disease. RAS examiners often connect current Nobel-linked discoveries with basic genetics and immunology.