Allelic methylation status of CpG islands on chromosome 21q in patients with Trisomy 21.

Trisomy 21 is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. There has been limited research into the DNA methylation status of CpG islands (CGIs) in trisomy 21, therefore, exploring the DNA methylation status of CGIs in 21q is essential for the development of a series of potential epigenetic biomarkers for prenatal screening of trisomy 21. First, DNA sequences of CGIs in 21q from the USCS database were obtained and 149 sequences and 148 pairs of primers in the BGI YH database were aligned. All 300 cases were analyzed by a heavy methyl-polymerase chain reaction (HM-PCR) assay and a comparison of the DNA methylation status of CGIs was made between trisomy 21 and the control. The HM-PCR assay results did not show a difference in the DNA methylation status between individuals with trisomy 21 and the control. In total, there were 11 CGIs that showed various DNA methylation statuses between Japanese and Chinese patients. Subsequently, bisulfite genomic sequencing found variations in the methylation status of CpG dinucleotides in CGIs (nos. 14, 75, 109, 134 and 146) between trisomy 21 and the control. The different DNA methylation status of CpG dinucleotides in CGIs may be a potential epigenetic marker for diagnosing trisomy 21. No difference was identified in the DNA methylation status of 21q CGIs among Chinese individuals with trisomy 21 and the control. The homogeneity of the DNA methylation status of 21q CGIs in Chinese patients indicates that DNA methylation is likely to be an epigenetic marker distinguishing ethnicities.

[1]  Stefan Wiemann,et al.  Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration , 2011, BMC Biology.

[2]  F. Tylavsky,et al.  Racial differences in gene-specific DNA methylation levels are present at birth. , 2011, Birth defects research. Part A, Clinical and molecular teratology.

[3]  N. Carter,et al.  Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21 , 2011, Nature Medicine.

[4]  E. Steegers,et al.  Congenital heart defects and biomarkers of methylation in children: a case–control study , 2011, European journal of clinical investigation.

[5]  Duan Ma,et al.  Hypomethylated DSCR4 is a placenta‐derived epigenetic marker for trisomy 21 , 2011, Prenatal diagnosis.

[6]  N. Schork,et al.  Altered DNA Methylation in Leukocytes with Trisomy 21 , 2010, PLoS genetics.

[7]  Y. Ono,et al.  Involvement of a centrosomal protein kendrin in the maintenance of centrosome cohesion by modulating Nek2A kinase activity. , 2010, Biochemical and biophysical research communications.

[8]  J. Ott,et al.  Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts , 2010, Human Genetics.

[9]  M. Barciszewska,et al.  Global DNA methylation changes in blood of patients with essential hypertension. , 2010, Medical science monitor : international medical journal of experimental and clinical research.

[10]  A. Andreadis,et al.  Heterogeneous nuclear ribonucleoprotein E3 modestly activates splicing of tau exon 10 via its proximal downstream intron, a hotspot for frontotemporal dementia mutations. , 2010, Gene.

[11]  C. Marian,et al.  Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women , 2009, Journal of cellular and molecular medicine.

[12]  N. Carter,et al.  Sites of differential DNA methylation between placenta and peripheral blood: molecular markers for noninvasive prenatal diagnosis of aneuploidies. , 2009, The American journal of pathology.

[13]  Dawei Li,et al.  The diploid genome sequence of an Asian individual , 2008, Nature.

[14]  A. Ugazio,et al.  Immunological features of Down's syndrome: a review. , 2008, Journal of intellectual disability research : JIDR.

[15]  C. Ding,et al.  Systematic search for placental DNA-methylation markers on chromosome 21: toward a maternal plasma-based epigenetic test for fetal trisomy 21. , 2008, Clinical chemistry.

[16]  C. Preudhomme,et al.  RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. , 2007, Blood.

[17]  N. Nowak,et al.  Familial 4.3 Mb duplication of 21q22 sheds new light on the Down syndrome critical region , 2007, Journal of Medical Genetics.

[18]  Chunming Ding,et al.  Hypermethylated RASSF1A in maternal plasma: A universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis. , 2006, Clinical chemistry.

[19]  A. Chango,et al.  Quantitative methylation-sensitive arbitrarily primed PCR method to determine differential genomic DNA methylation in Down Syndrome. , 2006, Biochemical and biophysical research communications.

[20]  E. Duh,et al.  Vascular endothelial growth factor upregulates expression of ADAMTS1 in endothelial cells through protein kinase C signaling. , 2006, Investigative ophthalmology & visual science.

[21]  Xin Gao,et al.  NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21 , 2006, Nature.

[22]  T. Richmond,et al.  Complex genomic alterations and gene expression in acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Sakharkar,et al.  Structural features differentiate the mechanisms between 2S (2 state) and 3S (3 state) folding homodimers , 2005, Bioinformation.

[24]  N. Shimizu,et al.  Identification of a novel zinc finger protein gene (ZNF298) in the GAP2 of human chromosome 21q. , 2005, Biochemical and biophysical research communications.

[25]  Kohki Kawane,et al.  Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis , 2005, Nature.

[26]  J. Byrd,et al.  Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia. , 2005, Cancer research.

[27]  K. Bushby,et al.  Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy , 2005, Journal of Medical Genetics.

[28]  G. Lubec,et al.  Metalloproteinase ADAMTS-1 but not ADAMTS-5 is manifold overexpressed in neurodegenerative disorders as Down syndrome, Alzheimer's and Pick's disease. , 2005, Brain Research. Molecular Brain Research.

[29]  R. Ball,et al.  Dysregulated Expression of Adamalysin-Thrombospondin Genes in Human Breast Carcinoma , 2004, Clinical Cancer Research.

[30]  J. Tangrea,et al.  A survey of gene-specific methylation in human prostate cancer among black and white men. , 2004, Cancer letters.

[31]  Yoshiyuki Sakaki,et al.  A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q. , 2004, Genome research.

[32]  Jurg Ott,et al.  A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis , 2003, Nature Genetics.

[33]  R. Hayes,et al.  Hypermethylation of GSTP1, CD44, and E‐cadherin genes in prostate cancer among US Blacks and Whites , 2003, The Prostate.

[34]  C. E. Arris,et al.  Expression of ADAMTS metalloproteinases in the retinal pigment epithelium derived cell line ARPE-19: transcriptional regulation by TNFalpha. , 2003, Biochimica et biophysica acta.

[35]  H. Vallance,et al.  A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. , 2003, Clinical biochemistry.

[36]  S. Rasmussen,et al.  Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study , 2002, The Lancet.

[37]  J. Rowley,et al.  Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[38]  S. Shott,et al.  Hearing loss in children with Down syndrome. , 2001, International journal of pediatric otorhinolaryngology.

[39]  R. Maki,et al.  Expression and activity of ADAMTS-5 in synovium. , 2001, European journal of biochemistry.

[40]  E. Hunter,et al.  A Conserved Tryptophan-Rich Motif in the Membrane-Proximal Region of the Human Immunodeficiency Virus Type 1 gp41 Ectodomain Is Important for Env-Mediated Fusion and Virus Infectivity , 1999, Journal of Virology.

[41]  G. Annéren,et al.  Thyroid dysfunction in Down’s syndrome: relation to age and thyroid autoimmunity , 1998, Archives of disease in childhood.

[42]  S. Liebhaber,et al.  Identification of two KH domain proteins in the alpha‐globin mRNP stability complex. , 1995, The EMBO journal.

[43]  L. Blomberg,et al.  Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Suqin Guo,et al.  Down Syndrome , 1989, Clinical pediatrics.

[45]  E. Hook,et al.  Down's syndrome: percentage reporting on birth certificates and single year maternal age risk rates for Ohio 1970-79: comparison with upstate New York data. , 1981, American journal of public health.

[46]  J. Lejeune,et al.  [Mongolism; a chromosomal disease (trisomy)]. , 1959, Bulletin de l'Academie nationale de medecine.

[47]  C. Ding,et al.  Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome-dosage approach. , 2010, Clinical chemistry.

[48]  F. Crea,et al.  Candidate epigenetic biomarkers for non-invasive prenatal diagnosis of Down syndrome. , 2007, Reproductive biomedicine online.

[49]  D. Patterson.  Genetic mechanisms involved in the phenotype of Down syndrome. , 2007, Mental retardation and developmental disabilities research reviews.

[50]  M. Sjöström,et al.  Novel mutations in the 5′-UTR of the FOLR1 gene , 2006, Clinical chemistry and laboratory medicine.