For couples concerned about passing on a hereditary disease or cancer to their children, in-vitro fertilization (IVF) with preimplantation genetic testing (PGT) may be a viable option.
Preimplantation genetic testing is used to screen embryos for hundreds of single gene disorders — like cystic fibrosis and Tay-Sachs — prior to implantation, significantly reducing the likelihood of future generations inheriting the disorder. However, the prevalence of single gene disorders is relatively rare when compared to the pervasiveness of complex (or polygenic) disorders that PGT cannot currently detect — like Type 2 diabetes, obesity and certain causes of dementia.
Polygenic Disorders: Multiple Genes and the Environment
According to the National Human Genome Research Institute, unlike diseases caused by a single gene mutation — like cystic fibrosis — with clear patterns of familial inheritance (Mendelian) and a unique set of health consequences, multi-gene disorders are caused by the complex interplay of multiple genetic mutations and environmental factors —like diet, lifestyle and exposure to viruses. Additionally, inheriting a polygenic disorder does not necessarily mean a person will express any symptoms of the disease, meaning that although diseases like diabetes appear to cluster in families, they do not display a clear pattern of inheritance (non-Mendelian) due to the interaction of genes and environment.
As advanced technology — like whole-genome sequencing — continues to reveal more information about the specific genetic mutations involved in polygenic disorders, what will the future of PGT for these multi-gene disorders look like?
The Ethics of PGT Use for Polygenic Disorders
The majority of organizations agree that PGT should test for severe or lethal childhood diseases, but the rise of testing for adult-onset disorders — like hereditary breast cancer and some forms of Alzheimer’s disease — raises some ethical questions about whether genetic disorders that could potentially be cured in the future should be screened.
However, the much more scientifically and ethically complicated question regards the future of PGT for screening embryos for multifactorial diseases like diabetes, congenital heart disease, certain types of dementia and some behavioral disorders, like autism.
According to a 2008 paper published in the journal Human Reproduction, in addition to screening embryos for hundreds of diseases caused by single genetic variants, PGT can also be used for gender selection of embryos that are at risk of inheriting a polygenic disorder that disproportionately affects either males or females. The paper considered the ethical implications of using PGT for gender selection of embryos predisposed to autism, which is known to affect males four fold over females.
The Future of Polygenic Disorders and PGT
While the majority of polygenic disorders cannot currently be identified with PGT because researchers do not have enough information on the genetics and environmental triggers involved, technology may soon close the gap. Researchers at Genomic Prediction advertise that they are coming out with a risk assessment model that “evaluates hundreds of thousands of genetic variants, implementing a novel combination of embryo genotyping methods not previously combined into a reproductive genetics application.”
Although the future of PGT for multi-gene disorders remains unclear, research into how these polygenic diseases are inherited and triggered by environmental elements isn’t slowing down. While most major organizations agree on the ethical uses of PGT, ongoing research will continue to open up new avenues for debate and consideration.
Dawn Michelle Lipscomb, PhD, is a biophysicist, podcast host, and science writer. While finishing a dual B.S. in Physics and Biology at UT San Antonio, she published research on planetary biosignatures for space exploration at NASA-JPL and designed THz bioeffects experiments for human tissues at the Air Force Research Laboratory. In 2017, she completed her Biophysics doctorate at UC Berkeley by developing a new method for imaging proteins that regulate gene expression using cryo-electron microscopy. Today, she co-hosts a live video podcast series on regenerative medicine and writes articles about groundbreaking research in aging and genetics.