Microchips may help improve prenatal diagnosis of Down syndrome

Washington, Nov 18 : Scientists at Baylor College of Medicine have established that a micro "chip" or array can prove effective in prenatal diagnosis of disorders such as Down syndrome or other diseases associated with chromosomal abnormalities.

In the study, led by Dr. Arthur Beaudet and Dr. Sau Wai Cheung at BCM, researcher examined 300 cases and described use of array comparative genomic hybridization to analyze samples taken during amniocentesis or chorionic villus sampling for chromosomal abnormalities.

Amniocentesis and chorionic villus sampling allow researchers to obtain foetal cells for testing.

"Larger studies of this test will help us decide whether it should be used as a first line measure to detect chromosome abnormalities in fetuses. They will also enable us to determine whether such testing should be offered more widely to pregnant women," said Beaudet.

"The array enables you to detect smaller deletions or duplications of genetic material that would not be seen on a regular karyotype (a depiction of the size, shape and number of chromosome and any abnormalities in them)," said Dr. Ignatia B. Van den Veyver, associate professor of obstetrics and gynecology and molecular and human genetics at BCM and first author of the report.

The scientists found that each of these deletions or duplications is rare but when added together, the rate of event could be as high as that seen in Down Syndrome.

She said that in some of these cases where small amounts of DNA are lost or duplicated, children often have significant learning disabilities or health problems that could not be picked up with an ultrasound or other means of prenatal diagnosis.

"This test adds information we could not detect by any other means right now in prenatal diagnosis," she said.

Array comparative genomic hybridisation provides the tools to scan foetal DNA quickly and automatically to identify copy number variation, which indicates the deletion or addition of genetic material at a particular point on the genome.

The array starts with single-stranded fragments of DNA embedded on a glass slide to form the array, which is then exposed to fluorescently labeled single-stranded DNA. Half of the labelled DNA is from the foetus being tested and is labelled with one fluorescent colour.

The other is reference DNA, which is labeled with another color. The fluorescently labeled DNA - reference and patient - binds to DNA on the array. The colour of the fragments will vary based on how much DNA from each binds to the DNA on the array.

If the foetus has DNA duplication, then the patient colour on the array will be stronger. If the foetus has a deletion, the reference colour will show up stronger. A specialized scanner evaluates the colour differences, which are then fed into a computer for analysis.

Majority of women in the study sought prenatal testing because they were older and faced a higher risk of having children with certain chromosomal abnormalities, such as Down syndrome.

Some had had abnormal ultrasounds and needed more information, and there were others had had children with a genetic abnormality previously.

"My conclusion is, that providing there is good genetic counseling that accompanies it, the test can be offered to prospective parents who want prenatal diagnosis. There are many parents interested in having this additional diagnostic information," said Van den Veyver.

She added: "If we use an array that is targeted and we have parental samples to confirm the meaning of detected changes, in the majority of cases, we will be able to counsel the patients about the significance of the findings."

The study appears in the current issue of the journal Prenatal Diagnosis.

ANI