A microarray-based approach for the identification of epigenetic biomarkers for the noninvasive diagnosis of fetal disease

• Published in: Prenatal diagnosis 2009-11, Vol.29 (11), p.1020-1030
• Main Authors: Chu, Tianjiao, Burke, Brian, Bunce, Kimberly, Surti, Urvashi, Allen Hogge, W., Peters, David G.
• Format: Article
• Language: English
• Subjects: Aneuploidy; Biological and medical sciences; biomarkers; Biomarkers - metabolism; Blood cells; Case-Control Studies; Chorionic Villi Sampling; chromosome 13; Chromosomes; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 18; Chromosomes, Human, Pair 21; Computer applications; CpG islands; Data processing; Delivery. Postpartum. Lactation; DNA; DNA Methylation; Epigenesis, Genetic - genetics; epigenetics; Female; fetal; Fetal Diseases - diagnosis; Fetal Diseases - genetics; Fetuses; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Genetics of eukaryotes. Biological and molecular evolution; Gynecology. Andrology. Obstetrics; High-Throughput Screening Assays - methods; Humans; Medical sciences; Models, Biological; Molecular and cellular biology; Oligonucleotide Array Sequence Analysis - methods; Oligonucleotides; Placenta; plasma; Pregnancy; Prenatal diagnosis; Prenatal Diagnosis - methods; Single-nucleotide polymorphism; Statistics; Villus
• ISSN: 0197-3851; 1097-0223; 1097-0223
• DOI: 10.1002/pd.2335

Objectives 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. Copyright © 2009 John Wiley & Sons, Ltd.