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.
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Authors | Debarati Ghosh, Swagata Sinha, Anindita Chatterjee, Krishnadas Nandagopal |
Journal | Disease markers
(Dis Markers)
Vol. 27
Issue 2
Pg. 45-54
( 2009)
ISSN: 1875-8630 [Electronic] United States |
PMID | 19893199
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Gluk1 kainate receptor
- Receptors, Kainic Acid
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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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