Sequencing all chromosomes to identify rare disease

BETHESDA, Md.—Extending noninvasive prenatal screening to all 24 human chromosomes can detect genetic disorders that may explain miscarriage and abnormalities during pregnancy, according to a study by researchers at the National Institutes of Health and other institutions. Because of the way data have been analyzed, typical genomic tests performed during pregnancy have targeted extra copies of chromosomes 21, 18 and 13, but rarely evaluated all 24 chromosomes. The study findings, which appear in the August 30 issue of Science Translational Medicine, may ultimately improve the accuracy of these tests, including by explaining why some give false-positive results.

“Extending our analysis to all chromosomes allowed us to identify risk for serious complications and potentially reduce false-positive results for Down syndrome and other genetic conditions,” said Dr. Diana W. Bianchi, senior author of the study and chief of the Prenatal Genomics and Therapy Section at NIH’s National Human Genome Research Institute (NHGRI).

The investigators analyzed DNA sequence data from nearly 90,000 samples of maternal plasma, the liquid portion of blood after all cells have been removed. Of these samples, 72,972 came from a U.S. cohort and 16,885 came from an Australian cohort.

“We found that pregnancies at greatest risk of serious complications were those with very high levels of abnormal cells in the placenta,” said Dr. Mark D. Pertile, co-first author of the study and head of the division of reproductive genetics at Victorian Clinical Genetics Services, part of Murdoch Childrens Research Institute in Melbourne, Australia. “Our results suggest that patients be given the option of receiving test results from all 24 chromosomes.”