Origin of nondisjunction in trisomy 21 syndrome: All studies compiled, parental age analysis, and international comparisons

Abstract

The Q-band polymorphism of chromosome 21 permits assignment of the origin of meiotic nondisjunction by parent and meiotic division in a certain proportion of cases. We have compiled all reports through 1982 (including earlier studies using structural abnormality) and have shown that maternal origin accounts for 80% and paternal origin for 20% of trisomic cases. The ratio of first:second meiotic errors among the maternal cases was 80:20 and 60:40 among the paternal cases. Considering maternal and paternal first and second meiotic errors, we showed no differences of either mean maternal or paternal age, though mean maternal age is about 5 yr higher than that of the general population. Comparison of results of six studies from five countries showed similar frequencies by parent and meiotic division with the possible exception of one study from the northeastern United States. The causative role of simply advancing maternal age in nondisjunction is questioned.

Chromosomal analysis of unfertilized human oocytes

“…It is believed that most meiotic chromosomal abnormalities occur in human females since various studies on the parental origin of the extra chromosome in Down syndrome have demon¬ strated that 70-80% are maternal in origin (Mattei et Juberg & Mowrey, 1983). Studies on spontaneous abortions suggest an even greater maternal contribution for other trisomies (Hassold et al, 1984).…”

Reliable detection of Trisomy 21 using MALDI-TOF mass spectrometry

“…No samples fell into the least certain category of possible affected. However, a single amniotic fluid supernatant sample exhibiting mosaicism for trisomy 21 (47, XX ϩ 21 [5]46, XX [21]) had an ASD value of 0.68 and was not identified as being abnormal with regard to chromosome 21 number.…”

“…Furthermore, this observation may be attributed to the fact that most cases of trisomy 21 are of maternal origin and arise from nondisjunction during meiosis I, rather than from nondisjunction during meiosis II, which would result in two identical chromosomes of maternal origin. 21,22 …”

“…10 -14 SNPs occur in the genome even more frequently than STRs, with on average one SNP found per kilobase. 15 Melting curve analysis of SNPs using amniotic fluid cell cultures has been shown to be able to distinguish between trisomic and normal samples for chromosome 21. 16,17 Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of SNPs has also been explored as an alternative diagnostic technique to karyotyping.…”

Analysis of the Origin of the Extra Chromosome in Trisomy 8 in 4 Cases of Spontaneous Abortions

“…Our main knowledge about chromosomal nondisjunction in humans comes from studies in trisomy 21 (Down syndrome), the most frequent of the autosomal trisomies in liveborns. The origin of nondisjunction in trisomy 21 was originally studied by chromosomal heteromorphisms [18,20], but the recombinant DNA technology allowed a more precise determination by DNA polymorphism analysis. In free trisomy 21, about 95% of the cases are of maternal origin [21,22], and among maternal errors approximately 75 and 25% are the result of nondisjunction in the first and in the second meiotic division of oogenesis, respectively [23].…”