Synthetic combinations of missense polymorphic genetic changes underlying Down syndrome susceptibility

• Published in: Cellular and molecular life sciences : CMLS 2016-11, Vol.73 (21), p.4001-4017
• Main Authors: Jackson, Rebecca A., Nguyen, Mai Linh, Barrett, Angela N., Tan, Yuan Yee, Choolani, Mahesh A., Chen, Ee Sin
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Chromosome aberrations; Down syndrome; Down Syndrome - genetics; Folic Acid - metabolism; Genetic Predisposition to Disease; Genotype & phenotype; Humans; Life Sciences; Molecular biology; Mutation, Missense - genetics; Polymorphism; Polymorphism, Single Nucleotide - genetics; Review; Tumor Suppressor Protein p53 - genetics
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-016-2276-0

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.