Please answer all questions The Online Mendelian Inheritance

Please answer all questions

The Online Mendelian Inheritance of Man (OMIM) is a catalog of known human genetic diseases. Go to OMIM at
http://www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM and search with the keyword “cystic fi brosis.” Examine the
OMIM record entitled “cystic fi brosis transmembrane conductance regulator.”
1. Look closely at the section on “Allelic Variants.” Is the delta-F508 mutation the only known alteration of the
CFTR gene?
2. As you look at the list of Allelic Variants (starting with .001), how does the information in brackets (e.g.,
[CFTR, PHE508DEL]) describe each mutation?
3. Th e CFTR gene contains how many exons? How many introns? Sketch a rough diagram of the exon/intron
structure of the CFTR gene.
4. For each mutation (allelic variant) listed below, explain how the mutation would aff ect the production of (1)
the mRNA and (2) the protein encoded by the CFTR gene. As an example, the fi rst case is completed for you.
• .0001 CYSTIC FIBROSIS [CFTR, PHE508DEL]
Th e 508th triplet codon, which normally codes for phenylalanine, is deleted. Consequently, the CFTR mRNA is 3
nucleotides shorter than normal, and the CFTR protein is one amino acid shorter, missing its 508th unit.
• .0003 CYSTIC FIBROSIS [CFTR, GLN493TER]
• .0004 CYSTIC FIBROSIS [CFTR, ASP110HIS]
• .0019 CYSTIC FIBROSIS [CFTR, 2-BP INS, 2566AT]
• .0008 CYSTIC FIBROSIS [CFTR, IVS10, G-A, -1]
• .0064 CYSTIC FIBROSIS [CFTR, IVS12, G-A, +1]
• .0123 CYSTIC FIBROSIS [CFTR, 21-KB DEL]
5. Sarah wondered how all these diff erent mutations can cause the same disease. As the genetic counselor, how
would you explain this to Sarah and Michael?

Solution

1. No delta-F508 mutation is one of the many alteration of the CFTR gene.