title: Polymorphisms in folate-metabolizing genes, chromosome damage, and risk of Down syndrome in Italian women: identification of key factors using artificial neural networks.
abstract: BACKGROUND
  Studies in mothers of Down syndrome individuals (MDS) point to a role for polymorphisms in folate metabolic genes in increasing chromosome damage and maternal risk for a Down syndrome (DS) pregnancy, suggesting complex gene-gene interactions. This study aimed to analyze a dataset of genetic and cytogenetic data in an Italian group of MDS and mothers of healthy children (control mothers) to assess the predictive capacity of artificial neural networks assembled in TWIST system in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being mother of a DS child.The dataset consisted of the following variables: the frequency of chromosome damage in peripheral lymphocytes (BNMN frequency) and the genotype for 7 common polymorphisms in folate metabolic genes (MTHFR 677C>T and 1298A>C, MTRR 66A>G, MTR 2756A>G, RFC1 80G>A and TYMS 28bp repeats and 1494 6bp deletion). Data were analysed using TWIST system in combination with supervised artificial neural networks, and a semantic connectivity map.
  
  
  RESULTS
  TWIST system selected 6 variables (BNMN frequency, MTHFR 677TT, RFC1 80AA, TYMS 1494 6bp +/+, TYMS 28bp 3R/3R and MTR 2756AA genotypes) that were subsequently used to discriminate between MDS and control mothers with 90% accuracy. The semantic connectivity map provided important information on the complex biological connections between the studied variables and the two conditions (being MDS or control mother).
  
  
  CONCLUSIONS
  Overall, the study suggests a link between polymorphisms in folate metabolic genes and DS risk in Italian women.
authors.affiliation: Department of Human and Environmental Sciences, Section of Medical Genetics, University of Pisa, Italy. f.coppede@geog.unipi.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
authors.forename: Enzo
authors.initials: E
authors.lastname: Grossi
authors.forename: Francesca
authors.initials: F
authors.lastname: Migheli
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
mesh_terms: D019540:Area Under Curve; D030541:Databases, Genetic; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007558:Italy; D053858:Metabolic Networks and Pathways; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D048629:Micronuclei, Chromosome-Defective; D016571:Neural Networks, Computer; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)