Sequencing all 24 human chromosomes uncovers rare disorders

August 30, 2017, NIH/National Human Genome Research Institute
Conceptual image of a cell karyotype exhibiting trisomy, three copies of one chromosome. Credit: Darryl Leja for NHGRI.

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.

Women often request noninvasive screening tests to detect genetic conditions. These tests, however, typically focus only on Down syndrome and other common trisomies. A trisomy is a condition in which there are three instances of a certain chromosome instead of the standard two.

"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 Diana W. Bianchi, M.D., senior author of the study and chief of the Prenatal Genomics and Therapy Section at NIH's National Human Genome Research Institute (NHGRI). Dr. Bianchi is also the director of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

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. For each, researchers calculated a normalized chromosome denominator quality (NCDQ), which measures the likelihood that a sample has the standard two copies of each chromosome. Those with an NCDQ of 50 or below were flagged for further evaluation.

In the U.S. cohort, 328 (0.45 percent) samples were flagged and ultimately classified as abnormal. In the Australian cohort, 71 (0.42 percent) samples were deemed abnormal, 60 of which contained a rare trisomy. Trisomy 7 was observed most frequently in both study cohorts, followed by trisomies 15, 16 and 22.

Pregnancy and other outcome data were available for 52 of the 60 cases of rare trisomies found in the Australian cohort. Notably, researchers linked 22 samples with early miscarriage (occurring before 11 or 12 weeks gestation), including 13 of 14 samples with trisomy 15 and 3 of 5 samples with trisomy 22.

"We found that pregnancies at greatest risk of serious complications were those with very high levels of abnormal cells in the placenta," said Mark D. Pertile, Ph.D., 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 ."

Explore further: Study finds NIPT detects more than 80 percent of chromosomal abnormalities

More information: Mark D. Pertile et al. Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease, Science Translational Medicine (2017). DOI: 10.1126/scitranslmed.aan1240

Related Stories

Study finds NIPT detects more than 80 percent of chromosomal abnormalities

February 3, 2014
In a study to be presented on Feb. 6 at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting, in New Orleans, researchers will report that noninvasive prenatal testing detected 83.2 percent of chromosomal ...

DNA test that identifies Down syndrome in pregnancy can also detect trisomy 18 and trisomy 13

February 2, 2012
A newly available DNA-based prenatal blood test that can identify a pregnancy with Down syndrome can also identify two additional chromosome abnormalities: trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). The ...

Some false postive prenatal genetic screens due to mother's extra DNA segments

April 2, 2015
Prenatal blood screening for extra or missing chromosomes in the fetus might give false-positive results if the mother's genome contains more than the usual number of certain DNA segments. This finding is reported April 1 ...

DNA test better than standard screens in identifying fetal chromosome abnormalities

February 27, 2014
A study in this week's New England Journal of Medicine potentially has significant implications for prenatal testing for major fetal chromosome abnormalities. The study found that in a head-to-head comparison of noninvasive ...

Latest study finds BGI's NIFTY test performs best in noninvasive prenatal screening

April 10, 2015
On April 1, 2015, researchers from the Baylor College of Medicine, the Chinese University of Hong Kong and the University of Hong Kong have published a study titled Accurate Description of DNA-Based Noninvasive Prenatal Screening ...

Blood test trumps accuracy of standard screening in detecting Down syndrome in early pregnancy

April 1, 2015
A blood test undertaken between 10 to 14 weeks of pregnancy may be more effective in diagnosing Down syndrome and two other less common chromosomal abnormalities than standard non-invasive screening techniques, according ...

Recommended for you

Air pollutants linked to abnormal fetal growth

February 23, 2018
Chinese mothers who were exposed to a high level of certain air pollutants during pregnancy had a higher risk of abnormal fetal growth, according to a new Yale School of Public Health (YSPH) study.

Scientists discover critical molecular biomarkers of preeclampsia

February 21, 2018
Preeclampsia, a sudden pregnancy complication that can interfere with the blood flow to the placenta and possibly to the fetus, can lead to low birth weight, prematurity and even death. It is also a leading cause of maternal ...

Transgender women can breastfeed, first case study shows

February 16, 2018
The first scientific case study has been published describing how a US transgender woman was able to breastfeed her adopted infant by taking hormones that induce lactation.

Controversial pregnancy test drug shows deformities in zebrafish embryos within hours of exposure

February 13, 2018
The components of a controversial drug, allegedly linked to birth defects in the 1960s and '70s, caused deformations to fish embryos just hours after they received a dose in new studies by researchers at the University of ...

Direct link between glands and implanting embryos critical to pregnancy

February 9, 2018
Researchers used 3D imaging with molecular testing to uncover new insight into the earliest stages of mammalian pregnancy—offering clues to unsolved questions in pregnancy.

Lab-grown eggs could pave way towards new fertility treatments

February 8, 2018
Human eggs have been fully grown in a laboratory, in a move that could lead to improved fertility treatments.

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

IronhorseA
not rated yet Aug 30, 2017
"to all 24 human chromosomes"

Does this mean that '23andme.com' will have to change their name? D~
FM79
not rated yet Aug 31, 2017
HUmans have 23 pairs of chromosomes...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.