Genetic analysis of over 200,000 British men suggests that around one in 500 have an extra sex chromosome. Most ignore it. Still, this observation is important because it could increase their risk of diseases like diabetes and cardiovascular problems. Details of the study are published in the journal Genetics in Medicine.
Sex chromosomes determine our biological sex. Males usually have one X chromosome and one Y chromosome, while females have two Xs. However, some males also have an extra X or Y chromosome (XXY or XYY). Population prevalence estimates are 100 per 100,000 men and 18 to 100 per 100,000 men respectively.
Men with Klinefelter syndrome (those with an extra X chromosome) typically present in adolescence with delayed puberty or in adulthood with infertility. Other characteristics include tall adult height, high body fat percentage, low muscle tone, low bone mineral density, and increased risk of neurocognitive impairment, psychoses, and personality disorders. Finally, the syndrome has also been associated with higher risks of type 2 diabetes.
On the other hand, the case of the extra Y chromosome is less well characterized. Affected males tend to be taller than boys and adults, but otherwise have no distinguishing physical characteristics.
In order to better understand their prevalence, a team from the University of Cambridge in collaboration with researchers from the University of Exeter analyzed data collected by the project UK Biobank. It is a biomedical database and research resource containing anonymised genetic information about the lifestyle and health of half a million UK participants. For this work, the researchers focused on genetic data collected from more than 200,000 British men between the ages of 40 and 70.
Scientists have identified 213 men with an X chromosome additional and 143 men with a Y additional. Taking into account the general health of the participants, the team calculated that approximately one in 500 men in the general population might carry an extra sex chromosome. This is a much higher percentage than previously thought.
Of the 213 cases with the extra X chromosome, only 49 (or 23%) were diagnosed with Klinefelter syndrome, while only one of the 143 men with an extra X chromosome Additional Y had been diagnosed. This is due to the reasons given in the preamble.
The researchers then studied the health of these participants and compared them to the rest of the population present in the database. It found that men with XXY chromosomes had significantly lower levels of testosterone in the blood. They also had a three times higher risk of delayed puberty and were four times more likely to be infertile. Men with an extra Y chromosome seemed to have normal reproductive function. In contrast, all men in these two cohorts were found to be at greater risk of developing type 2 diabetes, venous thrombosis, pulmonary embolism, or chronic obstructive pulmonary disease.
It is not yet known to the team why having an extra chromosome might increase these risks or why they appear similar in the two cases. Further work will be required to attempt to answer this question. Eventually, however, it might be worth starting to screen for the extra chromosomes as a potential way to prevent these various associated diseases .