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A new method for non-invasive prenatal diagnosis of Down syndrome using MeDIP real time qPCR

View Article: PubMed Central - PubMed

ABSTRACT

During the last decade, the area of non-invasive prenatal diagnosis (NIPD) has rapidly evolved. Several methodological approaches have been presented and demonstrated a proof of concept for the NIPD of chromosomal aneuploidies. The two most promising methods are NIPD using next generation sequencing technologies and NIPD using Methylation DNA Immunoprecipitation (MeDIP) with real time qPCR. Both approaches have been validated with blind studies and have > 99% accuracy. NIPD using next generation sequencing is achieved by high throughput shotgun sequencing of DNA from plasma of maternal women followed by ratio comparisons of each chromosome sequence tag density over the median tag density of all autosomes (z-score analysis). The MeDIP real time qPCR method, which is described in this review in more detail, is based on the identification of differentially methylated regions (DMRs) and their use in discriminating normal from abnormal cases. More than 10,000 DMRs were identified for chromosomes 13, 18, 21, X and Y using high resolution oligo-arrays that can be potentially used for the NIPD of aneuploidies for chromosomes 13, 18, 21, X and Y. Both NIPD methods have several advantages and limitations and it is believed that they will soon be implemented in clinical practice. With the continuous advancements of genetic methodologies and technologies, we predict that within the next 10 years we will be able to provide NIPD for all common and rare genetic disorders where the molecular basis is known.

No MeSH data available.


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From chromosomes to high resolution DNA analysis and from invasive to non-invasive prenatal diagnosis.
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f0015: From chromosomes to high resolution DNA analysis and from invasive to non-invasive prenatal diagnosis.

Mentions: Since the 1970s, prenatal diagnosis has been offered through the invasive procedures of CVS, amniocentesis and chordocentesis using chromosomal analysis, FISH and DNA methods (Fig. 3). With the rapid advances in technologies and methodologies, the scientific community has managed to increase the resolution of genome analysis. Such achievements permitted the detection of DNA defects from the size of megabases to single bases. These advances led from the karyotype and the detection of aneuploidies, to FISH and the identification of common microdeletion and subtelomeric rearrangements, to array CGH and identification of causative copy number changes, and currently to DNA molecular analyses and the identification of causative point mutations. It took us 50 years to move from the use of invasive prenatal diagnosis for chromosome analysis to the very high resolution genomic analyses and consequently this has led to the provision of prenatal diagnosis of an increasingly greater number of genetic disorders, as well as in significant improvements in accuracy (i.e. “more and better”) (Fig. 3).


A new method for non-invasive prenatal diagnosis of Down syndrome using MeDIP real time qPCR
From chromosomes to high resolution DNA analysis and from invasive to non-invasive prenatal diagnosis.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121212&req=5

f0015: From chromosomes to high resolution DNA analysis and from invasive to non-invasive prenatal diagnosis.
Mentions: Since the 1970s, prenatal diagnosis has been offered through the invasive procedures of CVS, amniocentesis and chordocentesis using chromosomal analysis, FISH and DNA methods (Fig. 3). With the rapid advances in technologies and methodologies, the scientific community has managed to increase the resolution of genome analysis. Such achievements permitted the detection of DNA defects from the size of megabases to single bases. These advances led from the karyotype and the detection of aneuploidies, to FISH and the identification of common microdeletion and subtelomeric rearrangements, to array CGH and identification of causative copy number changes, and currently to DNA molecular analyses and the identification of causative point mutations. It took us 50 years to move from the use of invasive prenatal diagnosis for chromosome analysis to the very high resolution genomic analyses and consequently this has led to the provision of prenatal diagnosis of an increasingly greater number of genetic disorders, as well as in significant improvements in accuracy (i.e. “more and better”) (Fig. 3).

View Article: PubMed Central - PubMed

ABSTRACT

During the last decade, the area of non-invasive prenatal diagnosis (NIPD) has rapidly evolved. Several methodological approaches have been presented and demonstrated a proof of concept for the NIPD of chromosomal aneuploidies. The two most promising methods are NIPD using next generation sequencing technologies and NIPD using Methylation DNA Immunoprecipitation (MeDIP) with real time qPCR. Both approaches have been validated with blind studies and have > 99% accuracy. NIPD using next generation sequencing is achieved by high throughput shotgun sequencing of DNA from plasma of maternal women followed by ratio comparisons of each chromosome sequence tag density over the median tag density of all autosomes (z-score analysis). The MeDIP real time qPCR method, which is described in this review in more detail, is based on the identification of differentially methylated regions (DMRs) and their use in discriminating normal from abnormal cases. More than 10,000 DMRs were identified for chromosomes 13, 18, 21, X and Y using high resolution oligo-arrays that can be potentially used for the NIPD of aneuploidies for chromosomes 13, 18, 21, X and Y. Both NIPD methods have several advantages and limitations and it is believed that they will soon be implemented in clinical practice. With the continuous advancements of genetic methodologies and technologies, we predict that within the next 10 years we will be able to provide NIPD for all common and rare genetic disorders where the molecular basis is known.

No MeSH data available.


Related in: MedlinePlus