TheMeiotic StageofNondisjunction inTrisomy21: Determination byUsingDNA Polymorphisms

Summary Wehavestudied DNA polymorphisms atloci inthepericentromeric region onthelong armofchromosome 21in200families withtrisomy 21,inorder todetermine themeiotic origin ofnondisjunction. Maintenance ofheterozygosity forparental markers intheindividual withtrisomy 21wasinterpreted asresulting froma meiosis Ierror, while reduction tohomozygosity wasattributed toameiosis IIerror. Nondisjunction was paternal in9cases andwasmaternal in188cases, asreported earlier. Amongthe188maternal cases, nondisjunction occurred inmeiosis Iin128cases andinmeiosis IIin38cases; in22cases theDNA markers used wereuninformative. Therefore meiosis Iwasresponsible for77.1%andmeiosis IIfor22.9%ofmaternal nondisjunction. Amongthe9paternal nondisjunction cases theerror occurred inmeiosis Iin2cases (22.2%) andinmeiosis IIin7(77.8%) cases. Since there wasnosignificant difference inthedistribution ofmaternal agesbetween maternal Ierror versus maternal IIerror, itisunlikely that anerror ataparticular meiotic stage contributes significantly totheincreasing incidence ofDownsyndrome withadvancing maternal age. Although theDNA polymorphisms usedwereatloci which mapclose tothecentromere, itislikely that rare errors inmeiotic-origin assignments mayhaveoccurred because ofasmall number ofcrossovers between themarkers andthecentromere. Analysis ofthese polymorphisms mayprovide amoreaccurate understandingofthemeiotic stage ofnondisjunction intrisomy 21thanthat previously provided bychromosomal heteromorphisms.