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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.
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.
The study by Haque and colleagues is an important contribution in the evolving field of prenatal testing. It provides a wealth of data on the frequency of genetic variants that can be detected in individuals of childbearing age from a diversity of racial/ethnic backgrounds. The large number of silent but potentially damaging sequence variants in every human genome went unnoticed until the last few years when high throughput DNA sequencing technology became widely available.
The study by Haque et al. was based on testing conducted by a commercial health technology company, although this does not in any way impugn the validity of the data presented. However, by using a proprietary testing strategy, some aspects of their approach are not reported in the article or otherwise ascertainable by the general public. For example, only the most frequently identified mutations are presented, and all those mutations are for disorders already offered in standard screening panels. Without supportive data to justify which diseases, genes, and mutations were selected, the screening panel may appear somewhat arbitrary and perhaps could be perceived as being driven by marketing concerns as much as by compelling scientific reasoning.
Wayne W. Grody, MD, PhD, is in the division of molecular diagnostics and at the Clinical Genomics Center at UCLA. He reported having no relevant financial disclosures. These comments are excerpted from an editorial accompanying Dr. Haque’s report (JAMA 2016;316:717-9).
The study by Haque and colleagues is an important contribution in the evolving field of prenatal testing. It provides a wealth of data on the frequency of genetic variants that can be detected in individuals of childbearing age from a diversity of racial/ethnic backgrounds. The large number of silent but potentially damaging sequence variants in every human genome went unnoticed until the last few years when high throughput DNA sequencing technology became widely available.
The study by Haque et al. was based on testing conducted by a commercial health technology company, although this does not in any way impugn the validity of the data presented. However, by using a proprietary testing strategy, some aspects of their approach are not reported in the article or otherwise ascertainable by the general public. For example, only the most frequently identified mutations are presented, and all those mutations are for disorders already offered in standard screening panels. Without supportive data to justify which diseases, genes, and mutations were selected, the screening panel may appear somewhat arbitrary and perhaps could be perceived as being driven by marketing concerns as much as by compelling scientific reasoning.
Wayne W. Grody, MD, PhD, is in the division of molecular diagnostics and at the Clinical Genomics Center at UCLA. He reported having no relevant financial disclosures. These comments are excerpted from an editorial accompanying Dr. Haque’s report (JAMA 2016;316:717-9).
The study by Haque and colleagues is an important contribution in the evolving field of prenatal testing. It provides a wealth of data on the frequency of genetic variants that can be detected in individuals of childbearing age from a diversity of racial/ethnic backgrounds. The large number of silent but potentially damaging sequence variants in every human genome went unnoticed until the last few years when high throughput DNA sequencing technology became widely available.
The study by Haque et al. was based on testing conducted by a commercial health technology company, although this does not in any way impugn the validity of the data presented. However, by using a proprietary testing strategy, some aspects of their approach are not reported in the article or otherwise ascertainable by the general public. For example, only the most frequently identified mutations are presented, and all those mutations are for disorders already offered in standard screening panels. Without supportive data to justify which diseases, genes, and mutations were selected, the screening panel may appear somewhat arbitrary and perhaps could be perceived as being driven by marketing concerns as much as by compelling scientific reasoning.
Wayne W. Grody, MD, PhD, is in the division of molecular diagnostics and at the Clinical Genomics Center at UCLA. He reported having no relevant financial disclosures. These comments are excerpted from an editorial accompanying Dr. Haque’s report (JAMA 2016;316:717-9).
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.
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.
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.
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.
FROM JAMA
Key clinical point: Expanded prenatal screening of prospective parents for genetic abnormalities would identify many more carriers of potentially serious disorders.
Major finding: An expanded carrier screening model that included additional severe and profound diseases would be expected to detect at least twice as many hypothetical fetuses as current professional screening recommendations (P less than .001 for all racial/ethnic categories).
Data source: An industry-sponsored retrospective modeling analysis involving data for 346,790 ethnically diverse men and women screened during a 3.5-year period.
Disclosures: 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.
