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Non-invasive prenatal diagnosis using cell-free fetal nucleic acids in maternal plasma: Progress overview beyond predictive and personalized diagnosis.

Tounta G, Kolialexi A, Papantoniou N, Tsangaris GT, Kanavakis E, Mavrou A - EPMA J (2011)

Bottom Line: The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma allowed for the development of alternative methodologies that may facilitate safe non-invasive prenatal diagnosis (NIPD).The low concentration of cffDNA in maternal plasma, however, and the coexistence of maternal DNA limit its clinical application to the detection or exclusion of fetal targets that are not present in the mother, such as Y chromosome sequences, the RHD gene in a RhD-negative woman and genetic conditions inherited from the father.Strategies for NIPD of monogenic disorders and fetal chromosomal aneuploidies have also been achieved using next-generation sequencing and could be introduced to the clinics as soon as cost-effective and high throughput protocols are developed.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, Athens University School of Medicine, Athens, Greece.

ABSTRACT
The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma allowed for the development of alternative methodologies that may facilitate safe non-invasive prenatal diagnosis (NIPD). The low concentration of cffDNA in maternal plasma, however, and the coexistence of maternal DNA limit its clinical application to the detection or exclusion of fetal targets that are not present in the mother, such as Y chromosome sequences, the RHD gene in a RhD-negative woman and genetic conditions inherited from the father. Strategies for NIPD of monogenic disorders and fetal chromosomal aneuploidies have also been achieved using next-generation sequencing and could be introduced to the clinics as soon as cost-effective and high throughput protocols are developed.

No MeSH data available.


Related in: MedlinePlus

General schema of DNA methylation analysis using methylation-sensitive restriction enzymes that selectively digest unmethylated DNA, so that only methylated fragments remain available for detection
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Fig1: General schema of DNA methylation analysis using methylation-sensitive restriction enzymes that selectively digest unmethylated DNA, so that only methylated fragments remain available for detection

Mentions: For this reason, researchers looked for fetal epigenetic markers that could be detected in maternal plasma without bisulphite conversion. Hypomethylated RASSF1A sequences derived from maternal blood cells can be removed from maternal plasma using methylation-sensitive restriction enzyme digestion, revealing only the fetal hypomethylated target (Fig. 1) [66]. Several studies demonstrated the value of using digestion resistant RASSF1A DNA sequences as a positive control for NIPD of fetal RhD status [66–68]. False-negative diagnosis can be avoided in samples that are negative for both RHD and RASSF1A sequences, as failure to detect hypermethylated RASSF1A sequences signifies the lack of fetal DNA in maternal plasma sample. These developments improve the reliability of the applications of cffDNA analysis when used in clinical setting.Fig. 1


Non-invasive prenatal diagnosis using cell-free fetal nucleic acids in maternal plasma: Progress overview beyond predictive and personalized diagnosis.

Tounta G, Kolialexi A, Papantoniou N, Tsangaris GT, Kanavakis E, Mavrou A - EPMA J (2011)

General schema of DNA methylation analysis using methylation-sensitive restriction enzymes that selectively digest unmethylated DNA, so that only methylated fragments remain available for detection
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3405386&req=5

Fig1: General schema of DNA methylation analysis using methylation-sensitive restriction enzymes that selectively digest unmethylated DNA, so that only methylated fragments remain available for detection
Mentions: For this reason, researchers looked for fetal epigenetic markers that could be detected in maternal plasma without bisulphite conversion. Hypomethylated RASSF1A sequences derived from maternal blood cells can be removed from maternal plasma using methylation-sensitive restriction enzyme digestion, revealing only the fetal hypomethylated target (Fig. 1) [66]. Several studies demonstrated the value of using digestion resistant RASSF1A DNA sequences as a positive control for NIPD of fetal RhD status [66–68]. False-negative diagnosis can be avoided in samples that are negative for both RHD and RASSF1A sequences, as failure to detect hypermethylated RASSF1A sequences signifies the lack of fetal DNA in maternal plasma sample. These developments improve the reliability of the applications of cffDNA analysis when used in clinical setting.Fig. 1

Bottom Line: The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma allowed for the development of alternative methodologies that may facilitate safe non-invasive prenatal diagnosis (NIPD).The low concentration of cffDNA in maternal plasma, however, and the coexistence of maternal DNA limit its clinical application to the detection or exclusion of fetal targets that are not present in the mother, such as Y chromosome sequences, the RHD gene in a RhD-negative woman and genetic conditions inherited from the father.Strategies for NIPD of monogenic disorders and fetal chromosomal aneuploidies have also been achieved using next-generation sequencing and could be introduced to the clinics as soon as cost-effective and high throughput protocols are developed.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, Athens University School of Medicine, Athens, Greece.

ABSTRACT
The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma allowed for the development of alternative methodologies that may facilitate safe non-invasive prenatal diagnosis (NIPD). The low concentration of cffDNA in maternal plasma, however, and the coexistence of maternal DNA limit its clinical application to the detection or exclusion of fetal targets that are not present in the mother, such as Y chromosome sequences, the RHD gene in a RhD-negative woman and genetic conditions inherited from the father. Strategies for NIPD of monogenic disorders and fetal chromosomal aneuploidies have also been achieved using next-generation sequencing and could be introduced to the clinics as soon as cost-effective and high throughput protocols are developed.

No MeSH data available.


Related in: MedlinePlus