In fact, Arnheim’s current research, which involves studying minute amounts of DNA taken from just one human sperm cell, would not be possible without the use of PCR. In his lab, researchers use PCR to learn how genes are shuffled, or recombined, within sperm cells, and how—when they become mutated in the human germline—they give rise to genetic diseases such as HD and genetic conditions such as achondroplasia (dwarfism).

By studying sperm from normal individuals and patients with HD and similar neurodegenerative genetic diseases, Arnheim has revealed much about the molecular basis of these diseases. They are all caused by a type of mutation called trinucleotide repeat expansion. While everyone carries a small number of repeating triplets of DNA letters (which might look like CAGCAGCAG…) in a gene called the huntingtin gene, people who develop HD have a much larger number. This number increases dramatically in the children of men with the disease.

Arnheim’s team continues work to uncover the molecular mechanisms underlying HD and other neurological diseases caused by abnormal numbers of trinucleotide repeats and other genetic changes. Recently, they have looked at achondroplasia, a kind of dwarfism that scientists have linked to inheritance of a single genetic change in the gene that encodes for a key growth protein. Arnheim and his graduate student Irene Tiemann-Boege have studied the sperm mutations in older men that cause this disease.

Their work contradicts a 40-year-old theory that cumulative sperm cell divisions over a man’s lifetime explained the increase in achondroplasia mutations seen in the sperm of older men. They are now testing a number of new hypotheses about the origins of the mutations that underlie this genetic condition.

Arnheim’s work to understand the fundamental mechanisms of mutation has been supported for the last decade by a prestigious MERIT award from the National Institutes of Health. This award also supported his work on genetic recombination. “There are specific chromosome regions where recombination takes place at higher rates,” he says. “Understanding this is a critical step in the search for the genetic basis of diseases thought to be influenced by multiple genes.”

To study these recombination patterns, however, required the development of a new technique that would allow Arnheim to investigate genes in greater detail. His team developed a new method of PCR that can detect even rare recombined genes with precision. “We believe that the technique will greatly speed the identification of the sites of recombination, with direct applications for understanding genetically based human disease, including those caused by chromosome abnormalities,” he says.

Although Arnheim categorizes himself as an experimental mammalian geneticist, his close collaborations with computational biologists have taught him to value the power that bioinformatics can bring to genetics. “We now have methods for rapidly collecting large amounts of data. We’re all running into the same problem. Once you’ve collected the data, how can you analyze it?” says Arnheim. That is where bioinformatics and computational biology come in. “The future of genetics lies in training people in both experimental and computational approaches. That way, they can make use of the mass of genetic data that has piled up,” he says.