4 The Origin of Numerical Chromosome Abnormalities

Publisher Summary This chapter reviews the origin of numerical chromosome abnormalities. Humans appear to be unique in their very high frequency of numerical chromosome abnormalities. The recent development of large numbers of molecular probes for all human chromosomes has provided the tools to enable the mechanisms underlying the high frequency of aneuploidy to be investigated. Earlier observations have concentrated on a small number of chromosomes, mainly those that are most frequently associated with aneuploidy. These investigations have shown a very wide diversity of mechanisms underlying numerical chromosome abnormalities. Also, the relative importance of the different mechanisms differs widely among chromosomes. With the exception of the 45,X, 47,XXY, and 47,XYY aneuploids, nondisjunction rarely involves a paternal chromosome and for the autosomes the proportion due to nondisjunction of a maternal chromosome ranges from 90 to 100%. The trisomies resulting from an error at maternal meiosis, a number of different mechanisms have been observed. These include errors of maternal MI (mat MI) and mat MII in which the nondisjoined chromosomes/chromatids show normal recombination, and errors of mat MI and mat MII in which the nondisjoined chromosome/chromatids show abnormal recombination. Abnormal recombination includes total absence of recombination, reduced recombination, and abnormally high levels of pericentromeric recombination.