NEW YORK (GenomeWeb) — Startup preconception genetic testing company GenePeeks has officially launched its sperm donor screening service, Matchright, with two partner sperm banks.
The service, which GenePeeks currently lists at $1,995, relies on a computer modeling strategy to combine sequence data from potential sperm donors with sequence data from a female customer, creating virtual gametes and then hundreds of thousands of virtual progeny each with their own virtual genotype. Based on whether or not any one of these genotypes is deemed to be at risk of conferring a diseased phenotype, donors are ruled in or out, creating a low-risk catalogue curated for each customer of the service.
According to the company's Co-founders Anne Morriss and Princeton molecular biologist Lee Silver, data from a small group of early adopters has suggested that, on average, about 80 percent of donors end up making the cut, while about 20 percent are found by the company's platform to harbor genetic alterations that could, in combination with alterations in a female customer's genome, produce an offspring with an inherited recessive disorder.
"That varies as you might expect from person to person," Silver said, "but that has been the average so far."
GenePeeks initially announced its business intentions at 2012's annual Consumer Genetics Conference in Boston. At the time, Silver said the company was working with microarrays, but planned to move to sequencing eventually.
With its commercial launch this month, Silver said Matchright is now solidly sequencing based. The company sequences donor and maternal DNA targeting the exons of 444 genes that he said "represent the best characterized and most significant of the rare recessive diseases."
Using an Illumina MiSeq, the company has already compiled a database of sequences from donors at its two partner sperm banks. When a customer seeks out the Matchright service, the same 444 genes are sequenced in her sample, and the company proceeds to perform its digital gamete and digital progeny calculations, yielding a personalized list of "safe" donors.
"We first create what we call virtual gametes, simulated haploid versions of the [maternal and paternal] sequences, and then bring them together into a virtual progeny. And we do that process about 1,000 times for each pairing," Silver explained.
"Each virtual progeny is a legitimate genomic sequence, [and though] it doesn't belong to anybody alive in the world," he said, "we can then use it to interrogate genome databases for disease associations [and] run modeling to understand the products of these 444 genes."
Essentially, Silver said, the company takes each of around 1,000 virtual progeny created for each donor pairing and simulates the protein that would be made by each copy of the 444 genes sequenced.
"If there is a clinically validated mutation, the program assumes a damaged gene product, and if not, we use modeling programs including PolyPhen [and others] to give us a likelihood of protein damage," he said.
According to Morriss, the screening is conservative. "For this particular service, we err on the side of safety and have created a very rigorous screen, where if we see any material evidence of risk we kick the donor out … a negative filter on a pool of donors."
Also central to GenePeeks' strategy is that neither sequence data for sperm donors nor women who order the test is analyzed or reported back, a feature that Silver has said keeps the service outside the purview of medical device regulation by the US Food and Drug Administration.
Morriss said women purchasing the service go through a consent process whereby they agree to relinquish access to their own sequence data.
The service also does not provide information about why donors are removed from a customer's personalized catalog because that could imply information about a woman's own carrier status.
According to Silver, the company has already seen evidence of the added value its strategy has over standard carrier screening methods in a small group of early adopters. "One of the things that was surprising for us was cystic fibrosis, which is something that everyone is already screened for and we didn't expect to see in our pairings, but in fact we did," he said.
The company has also seen at least one pairing that its platform found to be at risk for MCAD deficiency, the disease Morriss' son suffers from, and the impetus for her creation of GenePeeks.
"One of the things we are finding, with MCAD and with cystic fibrosis, is matches that fail because of a novel mutation that may have been seen before but had not been clinically validated," Silver said. "For example, we had a pairing where one chromosome had a clinically validated mutation, and the other had a mutation with 40 percent likelihood of damage. [In our system] that likelihood eliminated that pairing."
"This is risk that will never be seen in traditional carrier screening and demonstrates the kind of resolution we can get with our analysis that you can't get with carrier screens."
According to Morriss, the company is currently in conversations with potential new sperm bank partners.
GenePeeks also intends to eventually offer a screening service for couples, though the timeline on creating that product isn't yet clear.
"This technology could be very powerful for anyone planning a pregnancy in advance who wants to know the risks in advance," she said, "especially because we are intervening preconception and pre-pregnancy at a point where you have the most options."
Silver and Morriss acknowledged the scariness of this move in terms of its potential affect on relationships. But, Silver said, GenePeeks sees couples screening as something that would be actionable, especially as genomic technologies for preimplantation diagnosis and embryo selection continue to advance.
"If two people have mutations in a recessive disease gene, you would know what the mutations were, and you could take that info to a fertility clinic, go through [in vitro fertilization], and use PGD to avoid disease," he said.
"It's not going to be 'no baby for you,' or 'no husband for you,'" Morriss added. "We see it being a complement to PGD, where if the news back is not good, it's actionable and you can take these steps that people are increasingly taking."