title: Comprehensive investigation of DNA methylation and gene expression in trisomy 21 placenta.
abstract: Trisomy 21 (T21) is the most common aneuploidy affecting humans and is caused by an extra copy of all or part of chromosome 21 (chr21). DNA methylation is an epigenetic event that plays an important role in human diseases via regulation of gene expression. However, the integrative association between DNA methylation and gene expression in T21 fetal placenta has yet to be determined.
  
  
  
  We profiled expression of 207 genes on chr21 and their DNA methylation patterns in placenta samples from normal and DS fetuses using microarray analysis and predicted the functions of differentially expressed genes using bioinformatics tools.
  
  
  
  We found 47 genes with significantly increased expression in the T21 placenta compared to the normal placenta. Hypomethylation of the 47 genes was observed in the T21 placenta. Most of hypomethylated DNA positions were intragenic regions, i.e. regions inside a gene. Moreover, gene expression and hypomethylated DNA position showed significantly positive associations. By analyzing the properties of the gene-disease network, we found that increased genes in the T21 placenta were significantly associated with T21 and T21 complications such as mental retardation, neurobehavioral manifestations, and congenital abnormalities.
  
  
  
  To our knowledge, this is the first study to comprehensively survey the association between gene expression and DNA methylation in chr21 of the T21 fetal placenta. Our findings provide a broad overview of the relationships between gene expression and DNA methylation in the placentas of fetuses with T21 and could contribute to future research efforts concerning genes involvement in disease pathogenesis.
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, South Korea.
authors.forename: Ji Hyae
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, South Korea.
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea.
authors.forename: Jung Yeol
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, South Korea. Electronic address: sy5.park@cgh.co.kr.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, South Korea; Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea. Electronic address: hmryu@yahoo.com.
authors.forename: Hyun Mee
authors.initials: HM
authors.lastname: Ryu
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D019175:DNA Methylation; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
keywords: Chromosome 21; DNA methylation; Gene expression; Placenta; Trisomy 21