28. From Gene Mutation to Infertility
John Schimenti
John C. Schimenti, Biomedical Sciences, and one of his research colleagues discovered a gene mutation that causes infertility in male mice. This is the first time a dominant mutation that leads specifically to infertility in a mammal has been discovered. Similar mutations may exist in the DNA of some infertile men, although little is presently known about the genetic causes of infertility in humans. The gene, Dmc1, provides the code for a key protein involved in meiosis, the process that produces sperm and egg cells for reproduction. These sex cells contain only one set of chromosomes that combine during conception and create an embryonic cell with two chromosome sets, one from each parent. The mutation leads to a change in an amino acid in Dmc1 that blocks meiosis, preventing sperm production. The mutant allele (one version of the pair of genes inherited from each parent) is dominant. Females who carry it remain fertile, but pass the mutation on to future generations. The researchers discovered, however, that female carriers show higher rates of abnormalities during meiosis, which can potentially cause chromosome imbalances and birth defects. The researchers randomly induced mutations in the mouse genome and then looked for infertility in the resulting mice. The researchers aim to identify all the genes needed for fertility in mice and apply the information to the humans. Up to 15 percent of couples of childbearing age struggle with infertility.