Females lacking second X-chromosome may have started life 'male'

Turner Syndrome, a condition in which women have only one X chromosome instead of two, may be caused by a missing Y chromosome instead of a missing X as previously thought. Research published in Cell at the start of this month suggests that disruption in the Y chromosome can cause a range of male sex disorders including, surprisingly, Turner Syndrome which has always previously been considered a female sex disorder.

In females, the two X chromosomes can 'swap' sections of DNA during reproduction, a process known as recombination. Recombination helps to protect against the effects of deleterious mutations by ensuring a novel combination of gene material in the egg and the sperm, reducing the likelihood of a zygote carrying two X chromosomes with the same recessive mutation. However, the X and Y chromosomes are fundamentally different to each other and so cannot pair up and swap genetic material in this way. The Y chromosome has solved this problem by being 'palindromic' (having sections of DNA that are mirror images of other DNA sections) and instead recombining with itself during reproduction. The work published in the journal Cell this month has found further evidence for so-called 'self-recombination' in the Y chromosome, but also found that in some instances this process can cause more problems than it solves.

Professor David Page and his colleagues at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, US, analyzed the Y chromosomes of nearly 2,400 male patients with previously identified sexual abnormalities. They found that 51 of these Y chromosomes had two centromeres instead of one. So called 'isodicentric' Y chromosomes are inherently unstable and can fracture or even disintegrate entirely. Since the centromere is important for cell division, this Y-chromsome instability may have the potential to cause a range of disorders, according to Professor Page's work. He says: 'The same chromosome disorder [is] showing up in men who make few or no sperm but are otherwise healthy, and individuals who have various anomalies of sexual development at a broader anatomic level.'

Professor Page and colleagues have suggested that instead of a missing X chromosome, as previously thought, women with Turner Syndrome may in fact have a missing Y chromosome; A missing Y chromosome that may have disintegrated precisely because it was isodicentric and therefore unstable. 18 of the 51 patients Professor Page and colleagues found to have an isodicentric Y chromosome are anatomically female.

It is as yet unknown what proportion of Turner Syndrome cases can be explained by these findings. Professor Page suspects that these findings may be 'the tip of the iceberg.'