Molecular Diagnosis and Determination of the Parental Origin of Extrachromosome 21 in Korean with Down Syndrome Using DNA Haplotyping

ABSTRACT

Purposes: Down syndrome, the most common single cause of mental retardation, is usually due to meiotic nondisjunction leading to trisomy 21. In order to understand the mechanisms of meiotic nondisjunction including parental origin of an extrachromosome and the meiotic stage of nondisjunction, we have studied DNA polymorphisms at loci on the long arm of chromosome 21 in 36 families with free trisomy 21. METHODS: A total of 36 patients with Down syndrome who was cytogenetically diagnosed, and their parents were included in the study. The D21S11 locus was analysed using PCR follwed by denaturing polyacrylamide gel electrophoresis. RESULTS: The observed heterozygosity of D21S11 locus is 79.4% in the 104 unrelated Korean. Seven alleles with different sizes were observed. The parental origin of the extrachromosome 21 could be determined in 27 of 36 cases. The maternal origin was in 24 (88.9%) cases and paternal origin was in 3 cases (11.1%). Among informative cases, the meiotic error occurred at the first maternal meiosis in 9 (57.3%) cases and second meiosis in 7 (42.7%) of 16 cases. All paternal meiotic error occurred in the second meiosis. CONCLUSION: DNA haplotyping of the short tandem repeats markers can be very useful technique for molecular diagonosis and for determination of the parental origin of an extrachromosome 21 in Down syndrome. Nondisjunction of the maternal gamate is the main cause of trisomy 21, However, further studies with other polymorphic markers that locate at the centromere of chromosome 21 are needed in order to definitely determine the meiotic stage of nondisjunction in trisomy 21.