Will the woman want to know that she is an ApoE4 homozygote? What if the emotions associated with learning that information affect her decisions about having children? Did her family history reveal any information about the penetrance of that variant? Did her family history suggest any other potential risks? For example, diabetes is a huge public health challenge in the Bronx, which leads counseling strategies toward exercise and diet without genetics playing a substantial role.
The economics of genetic testing can be very difficult, Dolan concluded, because “we don’t really know what we are paying for.” Informed decision making is a laudable goal, but testing and counseling are expensive and will not necessarily lead to fewer affected infants. Nevertheless, the amount of disease that can be prevented is tremendous, as is the excitement surrounding genomics.
Arthur Beaudet, Henry and Emma Meyer Professor and chair of the Department of Molecular and Human Genetics, Baylor College of Medicine, discussed the case from the perspective of a futurist, looking at the kinds of capabilities and information that might be available 20 years from now. At that point, whole genome sequencing conducted in the first trimester using noninvasive techniques is likely to be common, he said. For the woman in the scenario, such testing would identify risk to her offspring caused by inherited conditions. It also would identify genetic risks related to new mutations, such as trisomies, point mutations, and deletions or duplications.
Beaudet divided the effects of genetic mutations into two categories. In the first category are debilitating conditions where individuals cannot live fully independently. Individuals affected in this way typically cannot advocate for themselves.
The second category includes conditions with milder severity. For these disorders, preimplantation genetic diagnosis becomes more of an option, said Beaudet. Examples might include breast cancer mutations, hereditary deafness, and achondroplasia.
From an economic perspective, whole genome sequencing will be more expensive than targeted testing, at least initially, but could be cost-effective if very expensive conditions are avoided, Beaudet said. If information provided to a patient or family from a whole genome sequence is limited, that restriction will be done not by designing a different test but by limiting the information to be shared. Also, from a multigenerational perspective, whole genome sequencing is far more cost-effective. If everyone has a whole genome sequence done at birth, it can be used throughout life, and the relevant information can be applied to other family members.