Sex cells, decoded: New technology has allowed scientists to sequence single sex cells from one individual to track rates of mutation--and possibly search for causes of infertility. Image: Layla Langfirstname.lastname@example.org
Less than a decade after the first full human genome was mapped, technology has arrived to decode the full genome of a single sex cell. The ability promises to offer new insight into the causes of infertility, the development of mutations and the diversity of the human genome.
Sperm and egg cells differ from other bodily cells in that they have a single—rather than double—set of chromosomes. Researchers have successfully amplified and sequenced 91 sperm cells from a single individual, a 40-year-old man whose genome has already been sequenced and analyzed—an important factor for checking the accuracy of the sperm sequencing. They found that the sampled sperm had sustained about 23 recombinations, which help to mix up genes from the chromosomes to increase genetic diversity in offspring, and between 25 and 36 new mutations, rates that match previous estimations for those in the general population. The scientists reported the findings online July 19 in Cell.
The new capability is "going to allow us to answer a lot of questions about genome stability in the germ line," says Don Conrad, a human geneticist at Washington University School of Medicine in Saint Louis, who was not involved with the new research. The researchers found that although the man who donated the sperm already had healthy offspring, two of the sperm cells studied were each missing a full chromosome. Such mutations, however, make it less likely that a sperm cell will successfully fertilize an egg.
Until now, we have made rough estimates about genetic mutations and recombination on the population scale. "We haven't had the tools to quantify those things on a personal level," Conrad says. "This is a technological breakthrough." Stephen Quake of the Stanford School of Medicine's Department of Bioengineering and his team have been working on this project for the past decade. "We started with bacteria and worked our way up to humans," he says. They harnessed developments in the field of micro-fluidics to sequence the single cells on chips. These micro-fluidic chips allowed them to amplify the genome (with a process called multiple displacement amplification) using far less material, which reduced the odds for contamination—and thus erroneous findings—by 1,000 times, they reported.
The approach also revealed new places where mutations seem to congregate on the genome—so-called hot spots. Although the study was not designed to pinpoint particular biological signals, it demonstrates "how little we actually knew about hot spots across the genome," Quake says. And future research can use these findings—and technology—to start to probe bigger biological questions, such as "to help understand and potentially diagnose reproductive disorders, to help understand what happens when it's the man's fault," he says.
Reproductive technologists, however, will not be sequencing sperm to screen them for implantation anytime soon. The current method of sequencing destroys the sperm cell subject. Quake, however, suggests that both screening and capturing a sperm cell intact is possible under the right conditions—namely, just before a sperm cell splits through meiosis. "If you can capture them before they separate, you can sequence one and you'll know what the other is."