Question

Ch 14: Mendell and the Gene Idea

A new genetic disorder is discovered. Not much is known about it other than the fact that inability to digest sugar is a symptom. Describe several inheritance patterns the disease may have, including descriptions of how each would affect its expression. Then briefly outline a method we could use to examine the genetics behind the disorder.

Answer 1

Ultimately, one wishes to determine how genes—and the proteins they encode—function in the intact organism. Although it may sound counterintuitive, one of the most direct ways to find out what a gene does is to see what happens to the organism when that gene is missing. Studying mutantorganisms that have acquired changes or deletions in their nucleotide sequences is a time-honored practice in biology. Because mutations can interrupt cellular processes, mutants often hold the key to understanding gene function. In the classical approach to the important field of genetics, one begins by isolating mutants that have an interesting or unusual appearance: fruit flies with white eyes or curly wings, for example. Working backward from the phenotype—the appearance or behavior of the individual—one then determines the organism's genotype, the form of the gene responsible for that characteristic .

Today, with numerous genome projects adding tens of thousands of nucleotide sequences to the public databases each day, the exploration of gene function often begins with a DNA sequence. Here the challenge is to translate sequence into function. One approach, discussed earlier in the chapter, is to search databases for well-characterized proteins that have similar amino acid sequences to the protein encoded by a new gene, and from there employ some of the methods described in the previous section to explore the gene's function further. But to tackle directly the problem of how a gene functions in a cell or organism, the most effective approach involves studying mutants that either lack the gene or express an altered version of it. Determining which cellular processes have been disrupted or compromised in such mutants will then frequently provide a window to a gene's biological role.

In this section, we describe several different approaches to determining a gene's function, whether one starts from a DNA sequence or from an organism with an interesting phenotype. We begin with the classical genetic approach to studying genes and gene function. These studies start with a genetic screen for isolating mutants of interest, and then proceed toward identification of the gene or genes responsible for the observed phenotype. We then review the collection of techniques that fall under the umbrella of reverse genetics, in which one begins with a gene or gene sequence and attempts to determine its function. This approach often involves some intelligent guesswork—searching for homologous sequences and determining when and where a gene is expressed—as well as generating mutant organisms and characterizing their phenotype.