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Aneuploidy (abnormal chromosome number) usually results from non-disjunction—failure of homologous chromosomes or sister chromatids to separate properly during meiosis I or II. Trisomy (three copies of a chromosome, e.g., Down syndrome/trisomy 21) and monosomy (one copy, e.g., Turner syndrome/45,X) cause severe gene dosage imbalances. Autosomes tolerate few aneuploidies; sex chromosomes tolerate more.
Diagram meiosis with non-disjunction in meiosis I and II, showing which gametes are unbalanced. Relate aneuploidy frequency to maternal age (increased in meiosis I due to age-related checkpoint failure). Consider why trisomy-21 is viable while trisomy of most other autosomes is lethal.
You already know that meiosis carefully separates homologous chromosomes (in meiosis I) and sister chromatids (in meiosis II) to produce haploid gametes with exactly one copy of each chromosome. Non-disjunction is what happens when this separation fails — a pair of chromosomes or chromatids moves to the same pole instead of splitting apart. The result is gametes with the wrong number of chromosomes: one gamete gets an extra copy and the other gets none. When these abnormal gametes fuse with a normal gamete at fertilization, the resulting embryo is aneuploid — it has a chromosome number that is not an exact multiple of the haploid set.
The two most common forms of aneuploidy are trisomy (2n + 1, three copies of one chromosome) and monosomy (2n − 1, only one copy). The consequences depend on which chromosome is affected and whether the error occurred in meiosis I or meiosis II. Non-disjunction in meiosis I is more severe because it affects homologous chromosomes: both members of a pair go to the same daughter cell, so all four resulting gametes are unbalanced — two have an extra chromosome and two are missing one. Non-disjunction in meiosis II affects sister chromatids, so only two of the four gametes are abnormal while the other two are normal. In humans, the frequency of meiosis I errors increases dramatically with maternal age, particularly after age 35, because oocytes arrested in meiosis I for decades accumulate deterioration of the cohesin proteins that hold homologous chromosomes together.
Most autosomal aneuploidies are lethal during embryonic development because they create massive gene dosage imbalances. Having three copies of a chromosome means producing roughly 50% more of every protein encoded on that chromosome, which disrupts the stoichiometry of protein complexes and regulatory networks. Only three human autosomal trisomies are compatible with live birth: trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome) — and the latter two are usually fatal within the first year. These particular trisomies survive partly because chromosomes 13, 18, and 21 are among the smallest and most gene-poor human chromosomes, so the dosage imbalance is relatively mild. Autosomal monosomies are almost universally lethal because losing an entire chromosome's worth of gene products is even more disruptive than gaining extra copies.
Sex chromosome aneuploidies are far better tolerated, and the reason connects to a mechanism you may encounter later: X-inactivation. In mammals, one X chromosome in each female cell is already silenced to equalize dosage between XX females and XY males. This means an XXY individual (Klinefelter syndrome) inactivates one X just like a typical female, and a 45,X individual (Turner syndrome) has only one active X — the same as both typical males and females. The extra or missing sex chromosome therefore causes relatively subtle phenotypic effects compared to autosomal aneuploidy, though fertility is usually impaired.