Better Screening for Deadly Genetic Diseases

One in 100 babies worldwide is born with a disease caused by a single gene, according to the World Health Organization. Two genetics companies—Counsyl and GoodStart Genetics—are now using low-cost sequencing as a way to provide a more comprehensive look at parents’ genes than has previously been available. The companies hope to better inform prospective parents about hidden single-gene diseases and potentially reduce their incidence.

Although most of these individual single-gene disease are rare, collectively they account for about 20 percent of infant deaths. When a disease gene is recessive, as is the case with sickle-cell anemia, Tay-Sachs, or cystic fibrosis, parents are unlikely to know they are carriers. If both parents carry a broken copy, they will have a 25 percent chance of having a child with the condition.

Doctors do screen prospective or expecting parents for a handful of diseases, but these tests are limited. Traditionally, the tests look for specific mutations for a particular disease, while the condition could be caused by many different mutations that are passed from generation to generation. “Generally, these tests top out at around 100 mutations,” says Gregory Porreca, a co-founder and vice president of research and technology at GoodStart Genetics. The reason is that every additional mutation will add cost, but the problem is that disease-causing mutations can be missed. For example, a traditional cystic fibrosis test would miss out on hundreds of disease-causing mutations—Porreca says that about 550 disease-causing mutations in the cystic fibrosis gene have been reported in the scientific literature. “With sequencing, you can look for all of them,” he says.

GoodStart Genetics uses sequencing technology from Illumina combined with proprietary methods of capturing genes of interest from a blood sample. The company offers tests for 23 different diseases, 15 of which are based on sequencing technology. The company launched in April 2012 and says it has processed over 100,000 tests. Counsyl began rolling out sequencing-based screening in January. The company screens for more than 100 different genetic disorders.

One option for parents who learn prior to conceiving that they both carry a mutation in the same recessive gene allele would be to use in-vitro fertilization (a costly and intensive procedure). With in-vitro fertilization, embryos can be tested for the presence of the disease before being implanted in the mother.

But whether comprehensive carrier screening will reduce the overall incidence of disease depends on the behaviors of the communities affected by it. In the last few decades, the number of children born with Tay-Sachs disease—a neurologically degenerative disorder that often takes a child’s life by the age of five and is relatively common among Ashkenazi Jews—has been reduced by 90 percent in that population in North America. That remarkable change was dependent on selective marriage based on screening and in utero testing.

But that example may be an exception rather than a rule. “It’s hypothetical that carrier testing on a broad scale would effectively reduce the incidence of genetic illnesses,” says Stephen Kingsmore, director of Pediatric Genomic Medicine at Children’s Mercy Hospital in Kansas City, Missouri. To better understand the power of comprehensive carrier screening, Kingsmore is running a long-term project in an Amish community to test whether sequencing-based carrier screening can reduce the incidence of disease.

Whether the screening will ultimately reduce babies born with genetic disease will, of course, ultimately depend on the decisions of the parents.