Creation of “virtual” children identifies risky sperm donor genomes for recipients

December 17, 2012Carole 7 Comments »

What characteristics  do you want in your sperm donor? Blue eyes? Brown hair? Would you like a six-foot two medical student who loves to play the saxophone or a five foot seven blonde tennis player? Or perhaps you’d like to find a sperm donor whose characteristics are a good match for your husband? Being able to select sperm donors based on a shopping list of characteristics is not a new phenomenon. Recently, I blogged about a company which uses facial recognition software to find look-alike matches to a preferred male face submitted by the recipient.  All of this information is useful for finding a good match for looks or blood type or other phenotypes that may or may not be reproduced in the child when sperm and egg are actually united and a new genetic person is created.

The genetic roll of the dice with a sperm donor is no different than the genetic roll of the dice with a sexual partner. The genes the child receives depends precisely on which sperm unites with which egg. Whether one gene or another gene is expressed depends on many factors including whether the gene is a recessive or dominant type. Recessive genes are those that are only expressed if both the male and female carry a copy of the recessive and the child inherits a recessive copy from each biological parent. If a child inherits both  a dominant gene and recessive gene for a trait, the recessive gene will stay quiet and the dominant gene will prevail and the child will express that dominant gene trait and not the recessive gene trait. When the recessive gene in question encodes the directions to cause a genetic disease, it certainly would be advantageous to be able to select a sperm donor who does not carry that recessive gene, making inheritance of two copies of the recessive –and therefore the disease- impossible.

Selection of a sperm donor based on genetic sequencing and virtual “recombination” may soon become reality.  A new start-up company called GenePeeks is gearing up to offer a new service sometime in the middle of 2013 which uses genetic sequencing to run virtual scenarios of the various options for genetic recombination that may arise between sperm from a donor and the recipient’s egg. In essence, you can try out various donors in advance before you purchase and use their sperm to fertilize your egg.

The impetus for this new testing service is based on the life experience of one of the co-founders, Anne Morriss.   She and her partner used a sperm donor to have a child. When her son was born, he was found to have a very severe genetic illness, Medium-chain acyl-CoA dehydrogenase deficiency (MCADD),  which made it impossible for him to utilize fats for energy.  This disease is often deadly. With immediate intervention and on-going management of his dietary intake, her son is thriving. However, in retrospect, if she could have chosen a donor that did not also carry the  MCADD recessive gene, she would have been able to ensure that her child could not receive that second recessive gene and could avoid developing the disease.  In 2010, Ms. Morriss and Dr. Lee Silver at Princeton co-founded  GenePeeks to give future parents another tool to select safer sperm donors to combine with their genetics. You can learn more about Anne and her personal story here. 

We all have recessive genes for genetic diseases. In order to benefit the most from this technology, we first have to know what dangerous genes we already carry before we can expressly exclude donors who carry similar recessives. Genepeeks will use DNA-scanning microarrays to sequence and analyze about 250,000 DNA bases in the genomes of both donors and recipients to look for problematic recombinations.  The next step is to run thousands of virtual simulations of possible child genomes between the donor and recipient. The disease risk of the various recombinations is calculated and dangerous donors can be excluded from use. Clients receive a customized list of lower risk sperm donors. The cost of this test is expected to be under $1000.00

GenePeeks is putting together a genetic counseling team for both donors and clients who purchase sperm. There are always some sticky ethical issues whenever genetic sequencing of the genome is discussed. Donors and clients will have the option of deciding whether they want to know about any genetic disease genes that are uncovered through genome sequencing. GenePeeks is planning to partner with a sperm bank, yet to be announced, sometime in 2013. More about the GenePeeks start-up can be found here.

This concept has been framed in terms of selecting less risky genetic matches when buying sperm from a sperm bank, but I think this genomic sequencing and virtual recombination analysis may be appealing to the general population. Why wouldn’t couples planning a pregnancy also want some advance warning of possible genetic risks they each carry in their genome? Risk assessment of virtual genomic matches can alert the couple that they have an elevated risk of having a child together with a dread disease. Not very romantic (!) but then neither is the pre-marriage blood test, still required in some states. Even if you and your beloved were found to be a risky match, high-tech reproduction could be used to reduce the risk.  IVF and pre-implantation genetic diagnosis (PGD) of IVF embryos could identify IVF embryos with and without the genetic disease genes. Embryos without the disease genes  can then be preferentially chosen for transfer.

I expect that those who fear that we are already sliding down the slippery slope to a brave new world of human engineering will not welcome yet another technological intervention in reproduction.  The old method of selecting sperm donors based only on mostly superficial physical characteristics like eye and hair color has little to recommend it when –if this technology works as advertised– parents could choose a better genetic match and reduce the risk of having a child with inherited health problems.  From this perspective, this technology may help every parent give their child a healthy start in life. isn’t that what every parent wants for their child?

I have contacted GenePeeks with some follow-up questions regarding validation of their test, cost, roll-out date and availability of this testing  to the general public. If they provide more information, I will update this post.

UPDATED INFORMATION:

Please see the responses from Professor Lee Silver, co-founder of Gene Peeks  to my questions below:

Q:How was the genome sequencing/matching probability method validated?

A: “The DNA chip we will use to genotype clients and donors is conservatively 99.99% accurate, validated through traditional double-blind testing. Our technology combines this data with well-understood laws of mathematics and genetics, which originated with Mendel’s experiments and have since been validated by a century of great science.  We are now in the middle of our final pre-launch production testing, which will predict discreet genomes for about a million virtual children. To validate the method, we’ll be comparing the incidence of the diseases we predict in these children with disease incidence in the general population.”

Q:How can patients be sure that all matches were considered?

A: “We digitally preview 1000 virtual children for each potential client/donor match, which is highly statistically significant for simple, single locus, recessive diseases (the diseases included in the first version of our product).  When we move into more genetically complex diseases such as severe autism, in order to approach the same level of confidence, that number will need to to 1,000,000 or more.”

I also asked about whether this testing service would only be available to clients looking for sperm donor matches and received these answers via Rebecca Silver, Director of Marketing, GenePeeks.

“To answer your second question, our current service is actually not infertility-exclusive at all. The technology we have allows any couple (fertile or non-fertile) to virtually combine their genomes before having kids to identify possibly genetic issues. Our first deployment of this technology is with partnering sperm banks. In conjunction with the sperm banks, all sperm bank clients will have their genomes virtually combined with all the sperm bank donors to identify and eliminate any client-donor matches that might increase the chance of the child inheriting a genetic disease. 
 
This is our first deployment of the technology, and down the line, we envision this service being offered to any couple interested in protecting the health of their future children. 
 
This service should be available through our first sperm bank partner in 6 months time, and the cost will be approximately $1,000.”

Fertility Lab Insider Disclaimer: I have no financial interest in this service or this company.

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© 2012, Carole. All rights reserved.

7 Responses to this entry

  • Just Another Science Nerd Says:

    “If one partner has a dominant gene for a trait, the recessive gene will stay quiet and the dominant gene will prevail and the child will inherit that dominant gene trait and not the recessive gene trait.”

    This is incorrect. If one partner has the dominant gene for a trait, the recessive gene will stay quiet and the dominant gene will prevail IN THE PHENOTYPE OF THE PARTNER. However, the child can inherit either the dominant or the recessive allele with equal frequency.

    That this is just a typo is inferred from following sentences, but I wanted to make sure this got fixed because understanding what dominant/recessive mean and don’t mean is one of the most major misunderstandings I’ve found in introductory biology courses. (E.g. that dominant genes can be rare or common, that dominant genes can be beneficial or detrimental, that dominant genes get selected with equal probability in meiosis to make gametes.)

  • Just Another Science Nerd Says:

    Perhaps what you mean is that if one partner carries ONLY the dominant gene?

    Regardless, interesting service and I’m very curious to see how this is received. With the advent of cheap recreational genome sequencing (e.g. 23andme.com), more and more people will be discovering that they are carriers for recessive disorders and checking their reproductive partners, and it would make sense to be able to check donors as well. Currently, donors with known recessive disorders are not allowed in programs, but truly, we all HAVE 5-6 recessive disorders that might be lethal if homozygous, so that seems not a particularly relevant policy.

  • Carole Says:

    Hi Just another Science Nerd,
    Thanks, your point is well-taken. I have clarified the sentence to make it clear I am talking about the phenotypic effect in the child if they do in fact inherit both recessive alleles (one possibility) or one dominant and one recessive allele (another possibility). They could also inherit two dominant alleles but that was not essential to the post.
    Carole

  • Carole Says:

    Does anyone who works with patients (genetic counselors, REs etc) — have you noticed whether more patients are coming in just for “defensive” genetic testing before they have a child- rather than patients who already know that they have a gene to be concerned about? I also wonder how this will be received.

  • Fertility Lab Insider - Lessons learned from over fifteen years of working inside fertility labs. » Blog Archive » GenePeeks Donor Bank Survey: 10$ Gift Card to Respondents Says:

    […] Creation of “virtual” children identifies risky sperm donor genomes for recipients […]

  • Just Another Science Nerd Says:

    Also, meant to say thank you for an incredibly informative and always enjoyable blog. It’s been a really fun way to hear more about things from other perspectives than my current/past roles as teacher and infertility patient.

  • Carole Says:

    HI Just Another Science Nerd,
    Thanks for the kind comment, You are welcome! 🙂 Best Wishes, Carole

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