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Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease
- Source :
- Sci Transl Med
- Publication Year :
- 2017
-
Abstract
- Whole-genome sequencing (WGS) of maternal plasma cell-free DNA (cfDNA) can potentially evaluate all 24 chromosomes to identify abnormalities of the placenta, fetus, or pregnant woman. Current bioinformatics algorithms typically only report on chromosomes 21, 18, 13, X, and Y; sequencing results from other chromosomes may be masked. We hypothesized that by systematically analyzing WGS data from all chromosomes, we could identify rare autosomal trisomies (RATs) to improve understanding of feto-placental biology. We analyzed two independent cohorts from clinical laboratories, both of which used a similar quality control parameter, normalized chromosome denominator quality. The entire data set included 89,817 samples. Samples flagged for analysis and classified as abnormal were 328 of 72,932 (0.45%) and 71 of 16,885 (0.42%) in cohorts 1 and 2, respectively. Clinical outcome data were available for 57 of 71 (80%) of abnormal cases in cohort 2. Visual analysis of WGS data demonstrated RATs, copy number variants, and extensive genome-wide imbalances. Trisomies 7, 15, 16, and 22 were the most frequently observed RATs in both cohorts. Cytogenetic or pregnancy outcome data were available in 52 of 60 (87%) of cases with RATs in cohort 2. Cases with RATs detected were associated with miscarriage, true fetal mosaicism, and confirmed or suspected uniparental disomy. Comparing the trisomic fraction with the fetal fraction allowed estimation of possible mosaicism. Analysis and reporting of aneuploidies in all chromosomes can clarify cases in which cfDNA findings on selected “target” chromosomes (21, 18, and 13) are discordant with the fetal karyotype and may identify pregnancies at risk of miscarriage and other complications.
- Subjects :
- 0301 basic medicine
Adult
Placenta Diseases
Chorionic villus sampling
Physiology
Trisomy
030105 genetics & heredity
Biology
Bioinformatics
Article
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Pregnancy
Risk Factors
medicine
Chromosomes, Human
Humans
Confined placental mosaicism
Demography
030219 obstetrics & reproductive medicine
medicine.diagnostic_test
Trisomy 16
Chromosome
Karyotype
General Medicine
Sequence Analysis, DNA
Placental disease
medicine.disease
Uniparental disomy
Fetal Diseases
Treatment Outcome
Chorionic Villi Sampling
Female
Cell-Free Nucleic Acids
Subjects
Details
- ISSN :
- 19466242
- Volume :
- 9
- Issue :
- 405
- Database :
- OpenAIRE
- Journal :
- Science translational medicine
- Accession number :
- edsair.doi.dedup.....68cad6a32b408979c7645b207e98fc29