Which of the following types of mutations would most likely lead to a frame-shift in the coding sequence of a gene?

A. A single nucleotide substitution in a coding region.
B. Insertion or deletion of a single nucleotide in a coding region.
C. A single nucleotide substitution in a non-coding region.
D. Insertion of a multiple of three nucleotides in a coding region.

Which combination of mutations would cause a frame-shift in the coding sequence?