The pseudoautosomal region behaves similarly to the autosomes during meiosis, allowing for segregation of the sex chromosomes. Just proximal to the pseudoautosomal region on the Y chromosome is the SRY gene (sex-determining region of the Y chromosome), which is critical for the normal development of male reproductive organs. When crossing over extends past the boundary of the pseudoautosomal region and includes this gene, sexual development will most likely be adversely affected. The rare occurrences of chromosomally XX males and XY females are due to such aberrant crossing over, in which the Y chromosome has lost—and the X chromosome has gained—this sex-determining gene.

Most crossing over is equal. However, unequal crossing over can and does occur. This form of recombination involves crossing over between nonallelic sequences on nonsister chromatids in a pair of homologues. In many cases, the DNA sequences located near the crossover event show substantial sequence similarity. When unequal crossing over occurs, the event leads to a deletion on one of the participating chromatids and an insertion on the other, which can lead to genetic disease, or even failure of development if a crucial gene is missing.

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