Noninvasive prenatal testing for fetal aneuploidy and single gene disorders

2017 ◽  
Vol 42 ◽  
pp. 26-38 ◽  
Author(s):  
Hannah Skrzypek ◽  
Lisa Hui
Keyword(s):  
Single Gene ◽  
Prenatal Testing ◽  
Noninvasive Prenatal Testing ◽  
Fetal Aneuploidy ◽  
Single Gene Disorders

scholarly journals Universal Haplotype-Based Noninvasive Prenatal Testing for Single Gene Diseases

2017 ◽  
Vol 63 (2) ◽  
pp. 513-524 ◽  
Author(s):  
Winnie W I Hui ◽  
Peiyong Jiang ◽  
Yu K Tong ◽  
Wing-Shan Lee ◽  
Yvonne K Y Cheng ◽  
...  
Keyword(s):  
Single Gene ◽  
Family Members ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Nucleotide Polymorphisms ◽  
Plasma Dna ◽  
Sequencing Technology ◽  
Noninvasive Prenatal Testing ◽  
Haplotype Phasing ◽  
Mutational Status

Abstract BACKGROUND Researchers have developed approaches for the noninvasive prenatal testing of single gene diseases. One approach that allows for the noninvasive assessment of both maternally and paternally inherited mutations involves the analysis of single nucleotide polymorphisms (SNPs) in maternal plasma DNA with reference to parental haplotype information. In the past, parental haplotypes were resolved by complex experimental methods or inferential approaches, such as through the analysis of DNA from other affected family members. Recently, microfluidics-based linked-read sequencing technology has become available and allows the direct haplotype phasing of the whole genome rapidly. We explored the feasibility of applying this direct haplotyping technology in noninvasive prenatal testing. METHODS We first resolved the haplotypes of parental genomes with the use of linked-read sequencing technology. Then, we identified SNPs within and flanking the genes of interest in maternal plasma DNA by targeted sequencing. Finally, we applied relative haplotype dosage analysis to deduce the mutation inheritance status of the fetus. RESULTS Haplotype phasing and relative haplotype dosage analysis of 12 out of 13 families were successfully achieved. The mutational status of these 12 fetuses was correctly classified. CONCLUSIONS High-throughput linked-read sequencing followed by maternal plasma-based relative haplotype dosage analysis represents a streamlined approach for noninvasive prenatal testing of inherited single gene diseases. The approach bypasses the need for mutation-specific assays and is not dependent on the availability of DNA from other affected family members. Thus, the approach is universally applicable to pregnancies at risk for the inheritance of a single gene disease.

Noninvasive Prenatal Testing for Fetal Aneuploidy

2013 ◽  
Vol 121 (4) ◽  
pp. 847-850 ◽  
Author(s):  
Mary E. Norton ◽  
Nancy C. Rose ◽  
Peter Benn
Keyword(s):  
Prenatal Testing ◽  
Noninvasive Prenatal Testing ◽  
Fetal Aneuploidy

scholarly journals Incidental Detection of Maternal Neoplasia in Noninvasive Prenatal Testing

2018 ◽  
Vol 64 (2) ◽  
pp. 329-335 ◽  
Author(s):  
Nilesh G Dharajiya ◽  
Daniel S Grosu ◽  
Daniel H Farkas ◽  
Ron M McCullough ◽  
Eyad Almasri ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Controlled Trial ◽  
Uterine Fibroids ◽  
Prenatal Testing ◽  
Circulating Tumor Dna ◽  
Malignant Neoplasms ◽  
Noninvasive Prenatal Testing ◽  
Fetal Aneuploidy ◽  
Depth Analysis

Abstract BACKGROUND Noninvasive prenatal testing (NIPT) uses cell-free DNA (cfDNA) as an analyte to detect copy-number alterations in the fetal genome. Because maternal and fetal cfDNA contributions are comingled, changes in the maternal genome can manifest as abnormal NIPT results. Circulating tumor DNA (ctDNA) present in cases of maternal neoplasia has the potential to distort the NIPT readout to a degree that prevents interpretation, resulting in a nonreportable test result for fetal aneuploidy. METHODS NIPT cases that showed a distortion from normal euploid genomic representation were communicated to the caregiving physician as nonreportable for fetal aneuploidy. Follow-up information was subsequently collected for these cases. More than 450000 pregnant patients who submitted samples for clinical laboratory testing >3 years are summarized. Additionally, in-depth analysis was performed for >79000 research-consented samples. RESULTS In total, 55 nonreportable NIPT cases with altered genomic profiles were cataloged. Of these, 43 had additional information available to enable follow-up. A maternal neoplasm was confirmed in 40 of these cases: 18 malignant, 20 benign uterine fibroids, and 2 with radiological confirmation but without pathological classification. CONCLUSIONS In a population of pregnant women who submitted a blood sample for cfDNA testing, an abnormal genomic profile not consistent with fetal abnormalities was detected in about 10 out of 100000 cases. A subset of these observations (18 of 43; 41.9%) was attributed to maternal malignant neoplasms. These observational results suggest the need for a controlled trial to evaluate the potential of using cfDNA as an early biomarker of cancer.

scholarly journals Initial clinical laboratory experience in noninvasive prenatal testing for fetal aneuploidy from maternal plasma DNA samples

2013 ◽  
Vol 33 (6) ◽  
pp. 569-574 ◽  
Author(s):  
Tracy Futch ◽  
John Spinosa ◽  
Sucheta Bhatt ◽  
Eileen Feo ◽  
Richard P. Rava ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Plasma Dna ◽  
Noninvasive Prenatal Testing ◽  
Laboratory Experience ◽  
Fetal Aneuploidy

Population Screening for Reproductive Risk for Single Gene Disorders in Australia: Now and the Future

2008 ◽  
Vol 11 (4) ◽  
pp. 422-430 ◽  
Author(s):  
Martin B. Delatycki
Keyword(s):  
Ethical Issues ◽  
Single Gene ◽  
Prenatal Testing ◽  
Genome Project ◽  
Population Screening ◽  
Reproductive Risk ◽  
Screening Programs ◽  
Single Gene Disorders ◽  
The Human Genome Project ◽  
Recessive Disorders

AbstractAs the results of the Human Genome Project are realized, it has become technically possible to identify carriers of numerous autosomal and X-linked recessive disorders. Couples at risk of having a child with one of these conditions have a number of reproductive options to avoid having a child with the condition should they wish. In Australia the haemoglobinopathies are the only group of conditions for which population screening is widely offered and which is government funded. In some Australian states there are also population screening programs for cystic fibrosis and autosomal recessive conditions more common in Ashkenazi Jewish individuals which are generally offered on a user pays basis. It is predicted that as consumer demand increases and testing becomes cheaper, that many people planning or in the early stages of pregnancy will have carrier screening for multiple genetic conditions. This will have significant implications for genetic counseling, laboratory and prenatal testing resources. In addition such screening raises a number of ethical issues including the value of lives of those born with genetic conditions for which screening is available.

Clinical validation and reporting of noninvasive prenatal testing for fetal aneuploidy detection

2021 ◽  
Vol 132 ◽  
pp. S322-S323
Author(s):  
Casey Brewer ◽  
Andy Pao ◽  
Linda Majors ◽  
Mariam Ghochani ◽  
Mike Moradian ◽  
...  
Keyword(s):  
Prenatal Testing ◽  
Clinical Validation ◽  
Noninvasive Prenatal Testing ◽  
Fetal Aneuploidy

scholarly journals Detection of chromosomal rearrangements in the short arms of chromosomes 4 and 12 as an example of a whole-genome approach to noninvasive prenatal testing

2019 ◽  
pp. 15-18
Author(s):  
A. Yu. Goltsov ◽  
I. S. Mukosey ◽  
T. O. Kochetkova ◽  
J. Shubina ◽  
M. V. Kuznetsova ◽  
...  
Keyword(s):  
Clinical Case ◽  
High Throughput Sequencing ◽  
Chromosomal Rearrangements ◽  
Prenatal Testing ◽  
Analytical Techniques ◽  
Molecular Karyotyping ◽  
Whole Genome ◽  
Noninvasive Prenatal Testing ◽  
Fetal Aneuploidy ◽  
Generation Sequencing

Timely detection of fetal aneuploidy is an important aspect of clinical practice. At present, analytical techniques involving high-throughput sequencing are on the rise. Noninvasive prenatal testing (NIPT) ensures reliable results as early as week 9–11 into pregnancy. This article describes a clinical case of NIPT application and further verification of its results. Using next-generation sequencing, the microarray analysis of cell-free DNA in the amniotic fluid and the cytogenetic analysis of fetal chromosomes, a high risk of chromosomal rearrangements was detected in the short arms of chromosomes 4 and 12. This prediction was verified by molecular karyotyping conducted in both parents. The mother was found to be a balanced carrier of translocations between chromosomes 4 and 12. This case demonstrates the advantages of a whole-genome approach to NIPT over targeted-based.

Sign in / Sign up

Export Citation Format

Share Document