Comparison of Mary's allelels with wild-type coding sequence.
Relative to the wild-type CFTR coding sequence, Mary’s allele A has a G to A mutation at position 360. (G360A)
Mary’s allele B has a G to A mutation at position 1652. (G1652A)
Comparison of protein sequence produced by Mary's alleles vs wild-type sequence.
Mary’s allele A is identical to the wild-type amino acid sequence, so the G to A mutation at position 360 must be a silent mutation (doesn’t change the amino-acid sequence).
Relative to the wild-type CFTR amino-acid sequence, Mary’s allele B has a glycine to aspartate change at position 551 (G551D).
Summary of Mary's CFTR alleles.
Mary’s molecular results agree with the genetic analysis that identifies her as a carrier: she has one allele (A) that will produce a wild-type CFTR protein, even though it has a one-nucleotide substitution (silent mutation) and one allele (B) that will produce a change in the CFTR protein (G551D). It must be allele B that she inherited from her mother, since we know Mary’s mother has CF and thus must have two defective CFTR alleles. Allele A must have come from Mary’s father.
Comparison of Tom's allelels with wild-type coding sequence.
Relative to the wild-type CFTR coding sequence, Tom’s allele A has a three-nucleotide deletion at position 1521.
Tom’s allele B is identical to the wild-type allele.
Comparison of protein sequence produced by Tom's alleles vs wild-type sequence.
Translation demonstrates that relative to the wild-type CFTR amino-acid sequence, Tom’s allele A has a phenylalanine (F) amino acid deleted at position 509.
Tom’s allele B is identical to the wild-type, and so they translate to the same amino acid sequence.
Summary of Tom's CFTR alleles.
This means that Tom is also a carrier for CF: he has one normal allele and one mutant allele.
Any child that Tom and Mary have has one chance in two of inheriting Tom’s mutant allele and one chance in two of inheriting Mary’s mutant allele. Even though they don’t have the same mutant alleles, the child then has one chance in four of inheriting a non-functional allele from each parent and having CF.