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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.
AuthorsDebarati Ghosh, Swagata Sinha, Anindita Chatterjee, Krishnadas Nandagopal
JournalDisease markers (Dis Markers) Vol. 27 Issue 2 Pg. 45-54 ( 2009) ISSN: 1875-8630 [Electronic] United States
PMID19893199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Gluk1 kainate receptor
  • Receptors, Kainic Acid
Topics
  • Child
  • Chromosomes, Human, Pair 21 (genetics)
  • Down Syndrome (genetics)
  • Female
  • Gene Frequency
  • Humans
  • Linkage Disequilibrium
  • Male
  • Meiosis
  • Polymerase Chain Reaction
  • Polymorphism, Genetic (genetics)
  • Polymorphism, Restriction Fragment Length
  • Receptors, Kainic Acid (genetics)

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