For the first time, researchers have developed a way to sequence the entire genome of a fetus by modifying the prenatal testing method known as amniocentesis. This groundbreaking finding, published in AACC’s journal Clinical Chemistry, could improve care for genetic diseases in childhood by dramatically increasing the number of these conditions that can be detected during pregnancy.
Amniocentesis is a common prenatal testing procedure that is used to detect the most common chromosomal abnormalities and genetic mutations in the fetus. It involves collecting amniotic fluid from the uterus of the pregnant mother, followed by analysis of fetal cells from this fluid with methods such as fluorescent in situ hybridization (FISH) and microarray, in addition to very targeted genetic testing. These analysis methods are the gold standard for diagnosing conditions such as Down syndrome and cystic fibrosis, however, these methods cannot detect the majority of disease-causing genetic alterations. A testing method is therefore needed that can detect a broader range of genetic mutations in order to better prepare parents for their child’s healthcare needs and ensure that affected infants receive treatment as soon as possible after birth.
A team of researchers led by Brock A. Peters, PhD, of Complete Genomics in San Jose, California, have shown that amniocentesis linked with whole-genome sequencing (WGS) can be used to analyze a fetus’ entire genome for harmful mutations. Peters’ team collected amniotic fluid from 31 pregnant women and isolated DNA from both the amniotic fluid and the fetal cells within it. They also collected DNA from the blood of each parent involved for comparison. On all three sets of DNA samples, WGS was then performed in place of FISH or microarray. Overall, the researchers found that WGS determined up to 97% of the fetal genome with confidence. Within the fetal genome, WGS identified almost all genetic mutations that were identified in the parental genomes. The researchers also sequenced saliva samples from 13 of the children after birth and determined that >92% of de novo mutations (a subset of genetic mutations) detected in the fetus also turned up in the newborn child.
Notably, there was no difference in quality between the sequencing results derived from amniotic fluid DNA versus fetal cell DNA. This is significant because leftover amniotic fluid is currently considered a waste product, and testing it could be an easy way to add WGS analysis to the overall amniocentesis procedure.
“We suggest the methods we have described here should be considered as an additional analysis that can augment current karyotyping data,” said Peters. “This type of additional information has the potential to identify many of the causes of serious birth defects that are currently missed. Finally, we believe a high-quality genome should be considered an investment in the child’s future, and having this information before the child’s birth can be enormously beneficial should any medical emergencies arise.”
Dedicated to achieving better health through laboratory medicine, AACC brings together more than 50,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, AACC has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation.
Clinical Chemistry is the leading international journal of clinical laboratory science, providing 2,000 pages per year of peer-reviewed papers that advance the science of the field. With an impact factor of 8.008, Clinical Chemistry covers everything from molecular diagnostics to laboratory management.