Genetic testing possible before conception.

Genetic testing possible before conception

It wasn't so long ago that a woman had to wait until her child was born before she knew whether it suffered from some genetic defect. Amniocentesis and, more recently, chorionic villus sampling have changed that, making genetic testing possible after only eight weeks of gestation. And newer techniques suggest that artificially inseminated embryos only a few hours old--as small as the eight-cell stage--may reveal their genetic abnormalities in the petri dish before being transferred to a mother's womb, allowing her to decide whether or not to proceed with the implantation (SN: 3/4/89, p.132).

Research now suggests that genetic testing may soon become feasible even in unfertilized eggs--clearly before conception. While such tests cannot evaluate the father's genetic contributions, they could prove valuable for women at high risk of giving birth to a child with a severe genetic defect.

So far, Yury Verlinsky and his colleagues at the Illinois Masonic Medical Center in Chicago have performed the sensitive analytic technique on eight eggs from one mother known to harbor a defective gene. Of the five eggs successfully tested, two came up negative for the defective gene and were implanted in her womb following in vitro fertilization. Although the woman did not become pregnant, the researchers say the testing technique worked well and appears not to have been a factor in the unsuccessful implantation. In vitro fertilization attempts typically have high failure rates.

To perform their analysis, the researchers take advantage of a natural quirk of egg production. While most human cells contain 46 chromosomes (23 from each parent), egg and sperm cells contain only half that number. During the specialized cell division that leads to the creation of egg cells, the leftover complement of 23 chromosomes gets packaged into a smaller cell called a polar body, which remains attached to the egg but eventually wastes away. In a woman who has inherited a normal gene from one parent and a defective version of the same gene from the other parent, the question of which gene her child will inherit boils down to one random event: Will the good gene end up in the mother's egg cell, or in that egg cell's polar body?

Direct tests on the egg would destroy that cell. So, after retrieving several eggs from the woman's ovary, Verlinsky and his co-workers carefully removed each egg's polar body and performed sensitive genetic tests on these. When the polar body harbored the normal gene, they knew the egg contained the abnormal one. When the polar body contained the abnormal gene, the researchers fertilized the corresponding egg with the husband's sperm and implanted the young embryo in the woman's uterus.

"This circumvents the possible need for elective termination" of pregnancy, Verlinsky said this week at the annual meeting of the American Society of Human Genetics in Baltimore. He predicts the technique will prove useful for a variety of recessive inherited defects such as cystic fibrosis, muscular dystrophy and Tay-Sachs disease. These diseases cause essentially no symptoms in individuals carrying only one defective gene but can kill when defective genes are inherited from both parents. In theory, Varlinsky's technique would ensure that a child would not inherit a defective gene from both parents.

Although the procedure is time consuming and costly--adding at least $5,000 to the current $10,000 price tag for a single, standard attempt at in vitro fertilization--it has already stirred considerable interest among women who could benefit, the researchers say.

In related research presented at the meeting, Diana W. Bianchi of the Children's Hospital in Boston reported progress toward a method of performing genetic tests on fetal red blood cells that have leaked through the placenta into the mother's circulation. Such leaks apparently occur after about 10 weeks' gestation. The procedure, which remains experimental, requires only a blood sample from the mother's arm, making it far less invasive than amniocentesis or chorionic villus sampling.