Diagnosis of Down Syndrome and Detection of Origin of Nondisjunction by Short Tandem Repeat Analysis

Context: Conventional karyotyping for antenatal diagnosis is time consuming and hence there has been a growing interest in more rapid techniques for detection of chromosomal aneuploidies. Around 95% of Down syndrome cases are due to free trisomy 21. Aims: The aims of this study were to demonstrate sensitivity of DNA diagnosis of Down syndrome using polymerase chain reaction (PCR) and short tandem repeat (STR) markers, and to determine the parental origin of the nondisjoined chromosome. Methods: DNA polymorphism was studied using two tetranucleotide STR markers, D21S2055 situated at 21q22.2 and D21S11 situated at 21q21.1. PCR conditions for both markers were standardized. PCR products were analyzed in 15% poly-acrylamide gels. The results obtained by STR analysis were verified with the chromosomal analysis and quantitative fluorescent (QF)-PCR. Results: These two STR markers were able to detect 86.7% cases of trisomy 21. Parental origin of extra chromosome was assigned to 77% of detected cases. Conclusion: The PCR-based DNA diagnostic method was found to be sensitive, reproducible, and efficient, not only for diagnosis of trisomy 21, but also for tracing allelic transmission from parents to the offspring.