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Circulating Fetal Cell-Free DNA Fractions Differ in Autosomal Aneuploidies and Monosomy X
- Source :
- Clinical Chemistry. 60:243-250
- Publication Year :
- 2014
- Publisher :
- Oxford University Press (OUP), 2014.
-
Abstract
- BACKGROUND Noninvasive prenatal testing based on massively parallel sequencing (MPS) of cell-free DNA in maternal plasma has become rapidly integrated into clinical practice for detecting fetal chromosomal aneuploidy. We directly determined the fetal fraction (FF) from results obtained with MPS tag counting and examined the relationships of FF to such biological parameters as fetal karyotype and maternal demographics. METHODS FF was determined from samples previously collected for the MELISSA (Maternal Blood Is Source to Accurately Diagnose Fetal Aneuploidy) study. Samples were resequenced, analyzed blindly, and aligned to the human genome (assembly hg19). FF was calculated in pregnancies with male or aneuploid fetuses by means of an equation that incorporated the ratio of the tags in these samples to those of a euploid training set. RESULTS The mean (SD) FF from euploid male pregnancies was 0.126 (0.052) (n = 160). Weak but statistically significant correlations were found between FF and the maternal body mass index (r2 = 0.18; P = 2.3 × 10−8) and between FF and gestational age (r2 = 0.02; P = 0.047). No relationship with maternal ethnicity or age was observed. Mean FF values for trisomies 21 (n = 90), 18 (n = 38), and 13 (n = 16) and for monosomy X (n = 20) were 0.135 (0.051), 0.089 (0.039), 0.090 (0.062), and 0.106 (0.045), respectively. CONCLUSIONS MPS tag-count data can be used to determine FF directly and accurately. Compared with male euploid fetuses, the FF is higher in maternal plasma when the fetus has trisomy 21 and is lower when the fetus has trisomy 18, 13, or monosomy X. The different biologies of these aneuploidies have practical implications for the determination of cutoff values, which in turn will affect the diagnostic sensitivity and specificity of the test.
- Subjects :
- Male
medicine.medical_specialty
Monosomy
Trisomy 13 Syndrome
Clinical Biochemistry
Turner Syndrome
Aneuploidy
Chromosome Disorders
Trisomy
Prenatal diagnosis
Biology
Sensitivity and Specificity
Fetus
Pregnancy
Prenatal Diagnosis
Internal medicine
medicine
Humans
Genetic Testing
Cell-Free System
Chromosomes, Human, Pair 13
Biochemistry (medical)
Gestational age
Karyotype
DNA
medicine.disease
Endocrinology
Female
Down Syndrome
Chromosomes, Human, Pair 18
Trisomy 18 Syndrome
Subjects
Details
- ISSN :
- 15308561 and 00099147
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Clinical Chemistry
- Accession number :
- edsair.doi.dedup.....808de0daa9ab5ba5786d79dedd350d3a