From prenatal genomic diagnosis to fetal personalized medicine: progress and challenges

Bianchi, Diana W.

doi:10.1038/nm.2829

Cited by 146 publications

(86 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Deletion/duplication syndromes are known to be associated with a wide range of structural and functional abnormalities (1), such as Cri du Chat Syndrome (5p deletion) (2) and DiGeorge Syndrome (22q11.2 deletion) (3). Such deletion/duplication syndromes can be reliably diagnosed prenatally from the DNA of fetal cells; fetal DNA may be assessed for chromosomal abnormalities by karyotyping, FISH, comparative genomic hybridization (CGH), and array-based technologies (4). G-banded karyotyping is the predominant technique for diagnosis of chromosomal abnormalities, but it is limited to resolution of 5-10 Mb (5,6).…”

mentioning

confidence: 99%

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA

Yin

Peng

Zhao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

105

124

View full text Add to dashboard Cite

Noninvasive prenatal testing (NIPT) using sequencing of fetal cellfree DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/ duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.noninvasive prenatal testing | NIPT | maternal plasma DNA | cell-free DNA | semiconductor sequencing G enomic disorders are defined by loss, gain, or translocation of chromosomal material. Deletion/duplication syndromes are known to be associated with a wide range of structural and functional abnormalities (1), such as Cri du Chat Syndrome (5p deletion) (2) and DiGeorge Syndrome (22q11.2 deletion) (3). Such deletion/duplication syndromes can be reliably diagnosed prenatally from the DNA of fetal cells; fetal DNA may be assessed for chromosomal abnormalities by karyotyping, FISH, comparative genomic hybridization (CGH), and array-based technologies (4). G-banded karyotyping is the predominant technique for diagnosis of chromosomal abnormalities, but it is limited to resolution of 5-10 Mb (5, 6). Genomic disorders of a smaller size are more reliably detected by chromosomal microarray analysis (CMA), of which array CGH (aCGH) is an example.According to The American Society of Human Genetics, CMA has replaced the standard metaphase karyotype in postnatal assessment of individuals with developmental delay, intellectual disability, congenital anomalies, and autism (7). In December of 2013, The American Congress of Obstetricians and Gynecologists and the Society of Maternal Fetal-Medicine recommended pr...

show abstract

mentioning

confidence: 99%

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA

Yin

Peng

Zhao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

105

124

View full text Add to dashboard Cite

show abstract

“…Given these technological developments, it is likely that some form of fetal genome testing will be available in the next few years. Others have noted that we might be reaching a point in the near-term future where it may be feasible to incorporate genetic, genomic and transcriptomic data to develop new approaches to fetal treatment [225,226].Our concern is that greed and financial conflicts of interest could lead to indiscriminate marketing and use of NIPS as diagnostic tests, rather than simply as screening, and that this technology will be implemented without any regard for genetic background or environmental differences, alongside a complete misunderstanding of this concept of extreme variability in phenotypic expression.…”

Section: Prenatal Diagnosis Preimplantation Genetic Diagnosis/screenmentioning

confidence: 99%

Human Genetics and Clinical Aspects of Neurodevelopmental Disorders

Lyon

O'Rawe

2015

The Genetics of Neurodevelopmental Disorders

View full text Add to dashboard Cite

“…8. The discovery that DNA circulates in the plasma [20] has led to array-or sequencing-based analysis of chromosomal abnormalities in birth defects [21] and this can potentially be exploited in cancers (including monitoring of recurrence) and through application to RNA. Circulating RNAs may be useable as tissue-specific biomarkers in a similar way to enzymes released from damaged tissues [22] .…”

Section: Technology Discovery and Laboratory Medicinementioning

confidence: 99%

Genetics and molecular biology in laboratory medicine, 1963–2013

Whitfield

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

The past 50 years have seen many changes in laboratory medicine, either as causes or consequences of increases in productivity and expansion of the range of information which can be provided. The drivers and facilitators of change in relation to clinical applications of molecular biology included the need for diagnostic tools for genetic diseases and technical advances such as PCR and sequencing. However, molecular biology techniques have proved to have far wider applications, from detection of infectious agents to molecular characterization of tumors. Journals such as Clinical Chemistry and Laboratory Medicine play an important role in communication of these advances to the laboratory medicine community and in publishing evaluations of their practical value.

show abstract

From prenatal genomic diagnosis to fetal personalized medicine: progress and challenges

Cited by 146 publications

References 118 publications

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA

Human Genetics and Clinical Aspects of Neurodevelopmental Disorders

Genetics and molecular biology in laboratory medicine, 1963–2013

Contact Info

Product

Resources

About