Expanded genetic screening of prospective parents for recessive abnormalities has the potential to identify many more carriers of potentially serious genetic disorders, compared with current screening that relies on racial/ethnic background, according to a report published online Aug. 16 in JAMA.
Currently, the American College of Medical Genetics and Genomics and the American Congress of Obstetricians and Gynecologists recommend prenatal carrier testing for only for a limited number of individual diseases and primarily based on parents’ reports of their racial/ethnic background. But new technologies now allow expanded carrier screening for dozens of conditions, and do so independently of parents’ racial/ethnic background, reported Imran S. Haque, PhD, of Counsyl, South San Francisco, Calif., and his colleagues. Counsyl is a commercial laboratory that provides expanded carrier screening.
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The researchers analyzed data from 346,790 individual screens performed between Jan. 1, 2012, and July 15, 2015, to create a computer model that estimates the results of expanded carrier screening. The model included 15 racial/ethnic categories, and it assessed screening results from either targeted genotyping or next-generation sequencing. The model assessed screens for up to 110 genetic abnormalities that cause up to 94 conditions known to produce profound or severe disability in affected offspring (JAMA. 2016;316[7]:734-42. doi: 10.1001/jama.2016.11139).
Across all racial/ethnic categories except African or African American or Southeast Asian, the expanded carrier screening model that included additional severe and profound diseases would be expected to detect at least twice as many hypothetical fetuses as would current professional screening recommendations (P less than .001 for all racial/ethnic categories).
For instance, among the Ashkenazi Jewish population, which has the most extensive ethnicity-specific panel, 55% of fetuses with profound or severe phenotypes would be missed using current screening (392.2 per 100,000 fetuses detected by expanded screening versus 174.8 per 100,000 with current screening). For the Middle Eastern population, 91% of fetuses with profound or severe phenotypes would be missed using the current screening (193.8 per 100,000 fetuses with expanded screening versus 17.7 per 100,000 fetuses with current screening).
Among couples of East Asian descent, expanded screening would identify genetic conditions affecting 129.9 per 100,000 fetuses, compared with 7.6 per 100,000 with current screening. Among couples of Northern European descent, expanded screening would identify genetic conditions affecting 159.2 per 100,000 fetuses, while current screening would do so in 55.2 per 100,000. Among couples of African descent, current screening misses about 13% of fetuses with profound or severe phenotypes, compared with expanded carrier screening.
The researchers noted that while carrier screening according to current guidelines targets “a number of diseases prevalent in those of European descent (such as cystic fibrosis), they do not identify risk for other conditions that may be important to diverse populations.”
“Expanded carrier screening revealed that many non-European racial/ethnic categories have a risk of a profound or severe genetic disease that may not be detected by the guidelines in place at the time of this analysis,” the researchers added.
Five of the study authors are employees of Counsyl, which funded the study. Another author disclosed ties with Natera Inc., Sequenom, Ariosa Diagnostics Inc./Roche, Illumina Inc., KellBenx, and Perinatal Quality Foundation.