On the origin of the supernumerary chromosome in autosomal trisomies ? with special reference to Down's syndrome

Abstract

The differential staining methods for chromosomes have led to the demonstration of more chromosomal polymorphisms. Not rarely, these polymorphisms allow in autosomal trisomies the detection of parental origin of the supernumerary chromosome. In addition, the malsegregation may be ascribed to 1st or 2nd meiotic division in informative families. This approach of analyzing possible causes of trisomies is subject to a considerable bias. Trisomic phenotypes are twice as frequent for 2nd meiotic errors than for 1st meiotic errors. Also, rare chromosome variants seldom occur in matings where malsegregation in 1st meiotic division can be detected. In the present paper this bias is analyzed mathematically on the family as well as on the population level. From this mathematical analysis and from the data in the literature we conclude that Down's syndrome as a whole is caused about 5-10 times more often by a malsegregation in 1st meiotic than by an error in 2nd meiotic division. Mainly from experimental studies in rodents, causes for errors in 1st and 2nd meiotic division are becoming apparent. They are summarized in the context of the results of the present paper.

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

“…Before 1976, by which time techniques had improved, a bias toward recognition of second meiotic divisional errors existed [Langenbeck et al, 1976;Roberts and Callow, 19801. Indeed, in our Table I there were altogether 30 identifications up to the Wagenbichler study [ 19761, and the ratio of nondisjunction was maternal first: maternal second: paternal first: paternal second = 0.37:O.…”

Clustering of chromosomal aneuploidy and tracing of nondisjunction in man.

“…In 43 patients with Down's syndrome the odd-numbered chromosome 21 originated from oogenesis (-70%) and in 19 cases (-30%o) from spermatogenesis. After we considered a serious bias in tracing nondisjunction involved with the use of chromosomal polymorphism it was concluded that first meiotic cleavage errors contribute at least 10 times more often to Down's syndrome than second meiotic cleavage errors (12). The same conclusion was drawn from another method of analysis (13) and from studies of abortions (14).…”

“…In our review of the literature on this subject (12) we summarized 62 cases which were informative with respect to the allocation ofnondisjunction. In 43 patients with Down's syndrome the odd-numbered chromosome 21 originated from oogenesis (-70%) and in 19 cases (-30%o) from spermatogenesis.…”

Reproductive and Developmental Toxicity of Metals: Female Reproductive System

“…These two forms of aneuploidy are believed to originate more commonly during oogenesis than spermatogenesis (Langenbeck et al, 1976;Jacobs and Morton, 1977) and during the first, rather than the second, meiotic division (Niikawa et al, 1977). Triploidy may also be due largely to ovular factors: either halving of chromosome number fails to occur, or surface components (zona pellucida and/or vitelline membrane) fail to block the entry of an additional spermatozoon.…”