title: A study of GluK1 kainate receptor polymorphisms in Down syndrome reveals allelic non-disjunction at 1173(C/T).
abstract: Mechanisms underlying Down syndrome (DS)-related mental retardation (MR) remain poorly understood. In trisomic offspring, non-disjunction may result in the reduction to homozygosity of a susceptibility allele inherited from a heterozygous parent. Accordingly, we sought evidence for allelic non-disjunction in the GluK1 gene that encodes the critical kainite-binding glutamate receptor subunit-5, maps to chromosome 21q22.1 in the DS critical region and is expressed in brain regions responsible for learning and memory. Three polymorphisms of GluK1 [522(A/C) rs363538; 1173(C/T) rs363430 and 2705(T/C) rs363504] were genotyped in 86 DS patient families by means of PCR-coupled RFLP assays and evaluated with respect to allele frequency, heterozygosity, linkage disequilibrium, stage and parental origin of allelic non-disjunction. We report that the distribution of allele frequencies is in Hardy-Weinberg equilibrium. Moderate heterozygosity (0.339) and a major allele frequency of 0.78 render the 1173(C/T) marker informative. Pair-wise comparisons reveal that 522(A/C)-1173(C/T) [chi<formula>;{2}</formula> = 31.2, df = 1, p = 0.0001; D' = 0.42] and 1173(C/T)-2705(T/C) [chi<formula>;{2}</formula> = 18.3, df = 1, p = 0.0001; D' = 0.34] are in significant linkage disequilibrium of weak magnitude. The estimated ratio of meiosis-I to meiosis-II errors arising from allelic non-disjunction of 1173(C/T) is 4:1 in maternal cases and 2:1 in paternal cases. Studies including additional markers and patient samples are warranted to further substantiate present findings.
authors.affiliation: Manovikas Biomedical Research & Diagnostic Centre, Kolkata-700107, India.
authors.forename: Debarati
authors.initials: D
authors.lastname: Ghosh
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.forename: Anindita
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Krishnadas
authors.initials: K
authors.lastname: Nandagopal
mesh_terms: D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008540:Meiosis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D018092:Kainic Acid Receptors / Q000235:genetics*
chemical_list: D018092:Kainic Acid Receptors