Disease specific characteristics of fetal epigenetic markers for non-invasive prenatal testing of trisomy 21Reportar como inadecuado




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BMC Medical Genomics

, 7:1

Prognostics and diagnostics-biomarkers

Abstract

BackgroundNon-invasive prenatal testing of trisomy 21 T21 is being actively investigated using fetal-specific epigenetic markers EPs that are present in maternal plasma. Recently, 12 EPs on chromosome 21 were identified based on tissue-specific epigenetic characteristics between placenta and blood, and demonstrated excellent clinical performance in the non-invasive detection of fetal T21. However, the disease-specific epigenetic characteristics of the EPs have not been established. Therefore, we validated the disease-specific epigenetic characteristics of these EPs for use in non-invasive detection of fetal T21.

MethodsWe performed a high-resolution tiling array analysis of human chromosome 21 using a methyl-CpG binding domain-based protein MBD method with whole blood samples from non-pregnant normal women, whole blood samples from pregnant normal women, placenta samples of normal fetuses, and placenta samples of T21 fetuses. Tiling array results were validated by bisulfite direct sequencing and qPCR.

ResultsAmong 12 EPs, only four EPs were confirmed to be hypermethylated in normal placenta and hypomethylated in blood. One of these four showed a severe discrepancy in the methylation patterns of T21 placenta samples, and another was located within a region of copy number variations. Thus, two EPs were confirmed to be potential fetal-specific markers based on their disease-specific epigenetic characteristics. The array results of these EPs were consisted with the results obtained by bisulfite direct sequencing and qPCR. Moreover, the two EPs were detected in maternal plasma.

ConclusionsWe validated that two EPs have the potential to be fetal-specific EPs which is consistent with their disease-specific epigenetic characteristics. The findings of this study suggest that disease-specific epigenetic characteristics should be considered in the development of fetal-specific EPs for non-invasive prenatal testing of T21.

KeywordsTrisomy 21 Non-invasive prenatal testing Epigenetic markers AbbreviationsT21Trisomy 21

NIPTNon-invasive prenatal testing

cff-DNACell-free fetal DNA

EPsEpigenetic markers

DMRsDifferentially methylated regions

CVSChorionic villus sampling

MBDMethyl-CpG binding domain-based protein

CNVsCopy number variations.

Electronic supplementary materialThe online version of this article doi:10.1186-1755-8794-7-1 contains supplementary material, which is available to authorized users.

Ji Hyae Lim, Da Eun Lee contributed equally to this work.

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Autor: Ji Hyae Lim - Da Eun Lee - So Yeon Park - Do Jin Kim - Hyun Kyong Ahn - You Jung Han - Moon Young Kim - Hyun Mee R

Fuente: https://link.springer.com/







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