Discerning non-disjunction in down syndrome patients by means of GluK1-(AGAT) n and D21S2055-(GATA) n microsatellites on chromosome 21.

ABSTRACT

Introduction: Down syndrome (DS), the leading genetic cause of mental retardation, stems from non-disjunction of chromosome 21. Aim: Our aim was to discern non-disjunction in DS patients by genotyping GluK1-(AGAT) n and D21S2055-(GATA) n microsatellites on chromosome 21 using a family-based study design. Materials and Methods: We have used a PCR and automated DNA sequencing followed by appropriate statistical analysis of genotype data for the present study Results and Discussion: We show that a high power of discrimination and a low probability of matching indicate that both markers may be used to distinguish between two unrelated individuals. That the D21S2055-(GATA) n allele distribution is evenly balanced, is indicated by a high power of exclusion [PE=0.280]. The estimated values of observed heterozygosity and polymorphism information content reveal that relative to GluK1-(AGAT) n [H obs =0.286], the D21S2055- (GATA) n [H obs =0.791] marker, is more informative. Though allele frequencies for both polymorphisms do not conform to Hardy-Weinberg equilibrium proportions, we were able to discern the parental origin of non-disjunction and also garnered evidence for triallelic (111) inheritance. The estimated proportion of meiosis-I to meiosis-II errors is 21 in maternal and 41 in paternal cases for GluK1-(AGAT) n , whereas for D21S2055-(GATA) n , the ratio is 21 in both maternal and paternal cases. Results underscore a need to systematically evaluate additional chromosome 21-specific markers in the context of non-disjunction DS.