Mendelian risk factors and embryo screening

2 minute read

The NYTimes has been very helpful for human geneticists lately, at least when it comes to providing good articles for class discussions. The latest is this article by Amy Harmon, titled "Couples cull embryos to halt heritage of cancer."

The article gives a good overview of preimplantation genetic diagnosis of embryos -- a technique that takes a single cell from an early-stage embryo in order to probe its DNA for undesirable alleles. The current twist, and really the hanger for the story, is that people who carry risk alleles for cancers and other late-life conditions are using the technique to avoid bearing children who carry their genetic "curse." PGD has been used for many years now to screen embryos that would inherit conditions like Tay-Sachs or cystic fibrosis. But testing for genes like BRCA1 may be perceived very differently, since the associated risks occur relatively late in life, and they are treatable (although certainly not always so). In other words, it is a different balance of risk versus fear.

Knowing that Mr. Kingsbury had tested positive for the colon cancer mutation, the Kingsburys started with the basic laws of genetics: because children randomly inherit half of each parent's genes, he had a 50 percent chance of passing it on. Since the mutation raises the risk of developing the cancer by about twentyfold, that means any child of theirs conceived the traditional way would have about a one in three chance of getting it, usually around age 45. Those who did develop the cancer would also have a nearly 90 percent chance of surviving it, but only if it was caught early.

The article talks about the procedure as becoming increasingly common, which is certainly true. But as I tell my students, there are pretty clear logical limits. Screening for one Mendelian gene is certainly possible, and has a reasonable chance of obtaining three or four "desirable" embryos if the couple starts with ten or twelve fertilized zygotes. But screen for two Mendelian genes at once, and you square the necessary number of fertilized eggs. The supply of ova is very limited, so picking offspring characteristics with PGD is not going to happen at any large scale.

Which, I would imagine, will increase the pressure for reproductive cloning. A father who carries a dominant cancer-risk gene can avoid passing it on entirely, if the couple decides to clone the mother instead.

Or maybe they will move on to deliberate chimerization. The father's colon cancer gene would be no problem, if all the progenitor cells for the reproductive tract were maternal clones. The rest of the child's body could be the normal fertilized child of both parents. Or a paternal clone.