title: SNaPshot Assay in Quantitative Detection of Allelic Nondisjunction in Down Syndrome.
abstract: OBJECTIVE
  We wished to identify markers associated with allelic nondisjunction in nuclear families with Down syndrome (DS) offspring. Since the GRIK1 and GARS-AIRS-GART genes, mapping to chromosome 21q22.1, may be informative in this regard, we genotyped four single-nucleotide polymorphisms [30952599(A/G) rs363484; 30924733(A/G) rs363506; 34901423(A/G) rs2834235; 34877070(A/G) rs7283354] present in these genes using the SNaPshot(™) assay protocol.
  
  
  RESULTS
  We have reported 30952599(A/G)-rs363484 to be monomorphic in our sample population. Genotyping revealed 35/65 families to be informative for 34877070(A/G)-rs7283354 (GARS-AIRS-GART), whereas only 25/65 and 11/65 are informative for 34901423(A/G)-rs2834235 (GARS-AIRS-GART) and 30924733(A/G)-rs363506 (GRIK1) polymorphisms, respectively. The parent- and stage-of-origin of nondisjunction could be traced in 48/65 families using at least one polymorphic marker. A single trio provided internal validation for assignment of the parent- and stage-of-origin of nondisjunction whereby the nondisjoining alleles were independently identified as G-rs363506, G-rs2834235, and G-rs7283354, respectively. An enhanced ratio of meiosis-I to meiosis-II errors during maternal or paternal meioses accounts for allelic nondisjunction.
  
  
  CONCLUSIONS
  The SNaPshot assay is quantitative and permits multiplexing for detection of allelic nondisjunction. Inclusion of additional informative chromosome 21-specific markers may aid rapid aneuploidy detection, screening, and prenatal counseling of parents at risk of having babies with DS.
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, Kolkata, India.
authors.forename: Debarati
authors.initials: D
authors.lastname: Ghosh
authors.forename: Sailesh
authors.initials: S
authors.lastname: Gochhait
authors.forename: Disha
authors.initials: D
authors.lastname: Banerjee
authors.forename: Anindita
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.forename: Krishnadas
authors.initials: K
authors.lastname: Nandagopal
mesh_terms: D000483:Alleles; D019731:Carbon-Nitrogen Ligases / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009630:Nondisjunction, Genetic; D051026:Phosphoribosylglycinamide Formyltransferase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018092:Kainic Acid Receptors / Q000235:genetics*
chemical_list: D019731:Carbon-Nitrogen Ligases; D051026:Phosphoribosylglycinamide Formyltransferase; D018092:Kainic Acid Receptors; C494823:GART protein, human