Compositions and Methods for Modifying Cells

A method for replacing an endogenous allele with a modified allele in a cell, the method comprising:

• (a) targeting the cell by homologous recombination with a targeting vector that comprises a DNA sequence of the modified allele;
• (b) exposing the DNA of the cell of with a first probe and a second probe, wherein the first probe binds within the endogenous allele but not within the modified allele, and the second probe binds within a reference gene but not within the endogenous allele and not within the modified allele, and wherein both probes generate a detectable signal upon binding, and wherein the reference gene is of known copy number;
• (c) detecting the signal from the binding of the first probe and the signal from the binding of the second probe;
• and
• (d) comparing the signal from the binding of the second probe to the signal from the binding of the first probe, and determining from the comparison a copy number of the endogenous allele.