What is it?            Marker analysis is a genetic technique whereby the sequence of the gene is not directly analyzed, but the mutant copy (allele) of the gene is inferred through analysis of a genetic marker. Genetic markers are polymorphic genetic sequences, such as microsatellites or RFLPs, which allow differentiation of the chromosomal alleles. Inheritance patterns within a family are traced and the mutant allele identified by comparing the alleles of affected and unaffected individuals. When is it used?            Marker analysis would be used, rather then direct examination of the gene, for several reasons: The gene location is known, but the gene sequence has not yet been determined and thus cannot be analyzed directly. But if markers exist close to the gene locus, then the mutant gene can be inferred through marker analysis. Marker analysis is much faster analysis then direct gene sequencing. Marker analysis is much cheaper then gene analysis. Marker analysis can generally be performed for under $200, while a complete screen of a gene can be several thousand dollars.
How Does it Work?            The figure on the right illustrates the relationship between the components of marker analysis. The gene and marker are located very close to each other on the same chromosome (sometimes the marker is located within the gene). The gene is mutated, but we do not analyze that mutation directly, but rather use the marker to identify which copy of the chromosome has the mutant gene on it.            Lets look at a family of four with an autosomal dominant genetic disease. All family members have two copies of the chromosome that has the gene (and marker) of interest on it. The mother has a genetic mutation and has a 50% chance of passing on the gene with the mutation to her offspring. The son inherits the chromosome (green) with the mutant gene on it and develops the disease. On the other hand, the daughter inherits the chromosome (pink) with the normal gene on it, thus does not get the disease.            If we did marker analysis on this family, we would not examine the gene or mutation directly. Rather, we would use a polymorphic marker (purple diamond) to try to identify the copy of the chromosome (green) with the mutated gene. The gel below shows microsatellite analysis of this family. To identify which allele is linked to the mutant gene, see if affected individuals have an allele in common that unaffected individuals do not have. In the gel, the affected mother and son share the bottom band on the gel. Thus we infer that the bottom (or green) allele is on the chromosome with the mutant gene. The unaffected daughter did not inherit this allele, thus is unlikely to develop the disease.
	The colorized representation of the gel corresponds to chromosome diagram above. The affected individuals share the green allele, thus we infer that the mutant gene is on the green allele. Offspring that inherit the green allele are at risk for developing the disease, while those who inherit the pink allele do not have an increased risk for the developing the disease.