Prenatal genetic testing of entire fetal genome: What is a healthy baby, anyway?

Prenatal Genetic Blueprint: What Is a Healthy Baby, Anyway?

Prenatal Genetic Blueprint: What Is a Healthy Baby, Anyway?

New Scientist
Stories from New Scientist.
Sept. 16 2012 7:15 AM

Do You Really Want To Know Your Baby’s Genetics?

New prenatal testing will bring anxiety and dilemmas.

Pregnant woman.
How much do you really want to know about the genetic profile of your fetus?

Photo by Creatas Images.

Boy or girl? This you can easily discover, but wouldn't you like to know more? If you could peer into your baby's medical future, what traits would you most want assurance about?

Most parents wouldn't hesitate: a healthy child. Soon science will be able to help them with that more quickly, completely—and safely—than ever before.

In June, a team at the University of Washington in Seattle announced a new technique that enables the construction of a comprehensive genome sequence—a genetic "blueprint," as they described it—of the developing fetus from as early as the first trimester (Science Translational Medicine, vol 4, p 137ra76). The test could be available in clinics in as little as five years.


Then, in July, a team at Stanford University announced a slightly different technique for obtaining the same information (Nature, vol 487, p 320).

Both techniques rely on the fact that fetal DNA circulates in the mother's bloodstream and can be isolated and sequenced. The Seattle test needs only a sample of saliva or blood from the father and blood from the mother. After determining the parents' genomes, it is possible to discern which DNA comes from the fetus. The Stanford test requires only maternal blood.

Both tests are noninvasive, thus avoiding the 2 percent risk of miscarriage posed by today's most common prenatal genetic tests: amniocentesis and chorionic villus sampling. These require a needle to be inserted into the amniotic sac so that the fetal DNA can be tested for Down's syndrome and other genetic disorders.

The existing prenatal tests can also spot other chromosomal abnormalities, including cystic fibrosis, trisomy 13, and Turner, Klinefelter, and fragile-X syndromes. In contrast, the genetic blueprint can finger thousands of potentially problematic genes. It is "like going from being able to see that two books are stuck together to being able to notice one word misspelled on a page," says Jacob Kitzman, a member of the University of Washington team.


The benefit is a medical early warning on a previously unknown scale. Children with the genetic disorder phenylketonuria, for example, are usually diagnosed after birth and must be put on a strict, lifelong diet. Knowing the child's status beforehand would be helpful.

Given this and other potential benefits, should we not hasten to make blueprint screening mandatory, as many newborn tests are today? Not until we know more, and maybe not even then.

Today, only around 5 percent of women who have prenatal tests receive bad news. Full genome screens will detect many more problems—and will introduce much more uncertainty because whole-genome mapping predicts the mere possibility of disease. Not all genetic anomalies are expressed as pathology.

The test will also produce false positives that frighten parents into thinking their child will have a disability when in fact he or she will be healthy.


For that matter, what is "healthy" anyway? When is a genetic anomaly a disease? Males with the chromosome disorder XYY were once thought to have a high risk of violent behavior, and many XYY fetuses were aborted. But research has shown that XYY males are essentially normal.

The price of genetic knowledge can be high because of the anxiety caused by the knowledge of a propensity for a disease that has no known treatment or cure, or that may never appear.

Before using such a test, parents must ask themselves, "What can we do with the information?" If abortion is not an option, perhaps because the fetus is past the maximum gestation period or because of moral beliefs, the information can be useless—or worse than useless, thanks to the needless anxiety. Moreover, the dearth of treatment options for some disorders makes the information medically useless, but potentially risky if insurers use it to hike rates or deny coverage.

If abortion is an option, new problems emerge: Which disorders justify abortion? For some conditions the choice is perhaps clearer. For example, children with the infantile form of Tay-Sachs or Canavan disease go into an immediate, inexorable decline. There is no cure or effective treatment and most children with the disease die in childhood.


But what of genes that entail a higher risk of Alzheimer's, typical prostate cancers, or Huntington's? These diseases emerge only after decades of productive life, and may not emerge at all.

Changing perceptions of disorders over time must also be taken into consideration. For example, we have seen a cultural sea change in the perception of Down's syndrome. Fifty years ago, parents were often advised to institutionalize affected children. Today, people with the condition mostly live in mainstream society and have found wide acceptance.

There are other ethically and legally sensitive issues. Who has a right to a child's genetic information? If the screen reveals an unmanageable condition such as Huntington's that will not manifest until the child is old enough to make his or her own decisions, should the parents decide whether to share the information with other family members who may share the risk? Should there be regulations that compel a physician or the parents to alert siblings and others who may be at high risk of harboring the gene?

The Seattle test can also reveal unexpected paternity. Should doctors have to disclose this, or should parents be able to opt out of being informed?

Whole-genome fetal sequencing is still years away from being used in the real world. It's a good thing, as we have a lot to sort out before then.

This article originally appeared in New Scientist.