A microarray-based approach for the identification of epigenetic biomarkers for the noninvasive diagnosis of fetal disease.
OBJECTIVE
We describe a novel microarray-based approach for the high-throughput discovery of epigenetic biomarkers for use in the noninvasive detection of fetal genetic disease.


METHODS
We combined a 215 060-probe custom oligonucleotide microarray with a comprehensive library preparation method and novel statistical tools to compare DNA methylation patterns in chorionic villus samples (CVS) with gestational age-matched maternal blood cell (MBC) samples. Our custom microarray was designed to provide high-resolution coverage across human chromosomes 13, 18 and 21.


RESULTS
We identified 6311 MspI/HpaII sites across all three chromosomes that displayed tissue-specific differential CpG methylation patterns. To maximize the probability of identifying biomarkers that have clinical utility we filtered our data to identify MspI/HpaII sites that are within 150 bp of a highly polymorphic single nucleotide polymorphism (SNP) so that its allelic ratio may be determined for the detection of fetal aneuploidy. Our microarray design and the computational tools used for data analysis are available for download as is the entire data set.


CONCLUSIONS
This high-resolution analysis of DNA methylation patterns in the human placenta during the first trimester of pregnancy identifies numerous potential biomarkers for the diagnosis of fetal aneuploidy on chromosomes 13, 18 and 21.
Chu
Tianjiao
T
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, PA 15213, USA.
Burke
Brian
B
Bunce
Kimberly
K
Surti
Urvashi
U
Allen Hogge
W
W
Peters
David G
DG
D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015193:Chorionic Villi Sampling; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D002891:Chromosomes, Human, Pair 21; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D020869:Gene Expression Profiling; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods
D015415:Biomarkers