title: Synthetic combinations of missense polymorphic genetic changes underlying Down syndrome susceptibility.
abstract: Single nucleotide polymorphisms (SNPs) are important biomolecular markers in health and disease. Down syndrome, or Trisomy 21, is the most frequently occurring chromosomal abnormality in live-born children. Here, we highlight associations between SNPs in several important enzymes involved in the one-carbon folate metabolic pathway and the elevated maternal risk of having a child with Down syndrome. Our survey highlights that the combination of SNPs may be a more reliable predictor of the Down syndrome phenotype than single SNPs alone. We also describe recent links between SNPs in p53 and its related pathway proteins and Down syndrome, as well as highlight several proteins that help to associate apoptosis and p53 signaling with the Down syndrome phenotype. In addition to a comprehensive review of the literature, we also demonstrate that several SNPs reside within the same regions as these Down syndrome-linked SNPs, and propose that these closely located nucleotide changes may provide new candidates for future exploration.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, #05-05, MD7, 8 Medical Drive, Singapore, 117597, Singapore.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Jackson
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, #05-05, MD7, 8 Medical Drive, Singapore, 117597, Singapore.
authors.forename: Mai Linh
authors.initials: ML
authors.lastname: Nguyen
authors.affiliation: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, #05-05, MD7, 8 Medical Drive, Singapore, 117597, Singapore.
authors.forename: Angela N
authors.initials: AN
authors.lastname: Barrett
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, #05-05, MD7, 8 Medical Drive, Singapore, 117597, Singapore.
authors.forename: Yuan Yee
authors.initials: YY
authors.lastname: Tan
authors.affiliation: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, #05-05, MD7, 8 Medical Drive, Singapore, 117597, Singapore. mahesh_a_choolani@nuhs.edu.sg.|National University Health System, Singapore, Singapore. mahesh_a_choolani@nuhs.edu.sg.
authors.forename: Mahesh A
authors.initials: MA
authors.lastname: Choolani
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, #05-05, MD7, 8 Medical Drive, Singapore, 117597, Singapore. bchces@nus.edu.sg.|National University Health System, Singapore, Singapore. bchces@nus.edu.sg.|NUS Graduate School of Science and Engineering, National University of Singapore, Singapore, Singapore. bchces@nus.edu.sg.
authors.forename: Ee Sin
authors.initials: ES
authors.lastname: Chen
mesh_terms: D004314:Down Syndrome / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53; D005492:Folic Acid
keywords: Folate; MTHFR; Missense; One-carbon metabolism; Polymorphism; SNP; Trisomy 21; p53