Chapter 5, Problem 51P

Neurofibromas are tumors of the skin that can arise when a skin cell that is originally NF1⁺/NF1^- loses the NF1⁺ allele. This wild-type allele encodes a functional protein (called a tumor suppressor), while the NF1^- allele encodes a nonfunctional protein.

A patient of genotype NF1⁺/NF1^- has 20 independent tumors in different areas of the skin. Samples are taken ofnormal, noncancerous cells from this patient, as well as of cells from each of the 20 tumors. Extracts of these samples are analyzed by a technique called gel electrophoresis that can detect variant forms of four different proteins (A, B, C, and D) all encoded by genes that lie on the same autosome as NF1. Each protein has a slow (S) and a fast (F) form that are encoded by different alleles (for example, A^S and A^F ). In the extract of normal tissue, slow and fast variants of all four proteins are found. In the extracts of the tumors, 12 had only the fast variants of proteins A and D but both the fast and slow variants of proteins B and C; 6 had only the fast variant of protein A but both the fast and slow variants of proteins B, C, and D; and the remaining 2 tumor extracts had only the fast variant of protein A, only the slow variant of protein B, the fast and slow variants of protein C, and only the fast variant of protein D.

a.	What kind of genetic event described in this chapter could cause all 20 tumors, assuming that all the tumors are produced by the same mechanism?
b.	Draw a genetic map describing these data, assuming that this small sample represents all the types of tumors that could be formed by the same mechanism in this patient. Show which alleles of which genes lie on the two homologous chromosomes. Indicate all relative distances that can be estimated. Note that NF1 is one of the genes you can map in this way.
c.	Another mechanism that can lead to neurofibromas in this patient is a mitotic error producing cells with 45 rather than the normal 46 chromosomes. How can this mechanism cause tumors? How do you know, just from the results described, that none of these 20 tumors is formed by such mitotic errors?
d.	Can you think of any other type of error that could produce the results described?