Chris Kaposy considers the implications of a study showing that having an extra chromosome is much more common than previously thought.

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A recent study in the UK gives us reason to re-think some assumptions about genetic normality and abnormality. A human being with a “normal” complement of chromosomes has 46 – or 23 pairs, so we think. More than 46 or fewer gives one a genetic abnormality, or a syndrome.

However, this study, published in the journal Genetics in Medicine shows that more people than previously suspected have 47 chromosomes. And the vast majority of these people have no idea that they have an extra chromosome.

The study was simple in its design. The researchers accessed the genetic material of over 207,000 men of European ancestry deposited in the UK Biobank. They analyzed the genotypes of all of these men, and then analyzed their health data in relation to their genotypes. Researchers identified 213 men with an extra X chromosome – a condition also known as “47,XXY” or “Klinefelter syndrome”. They also found 143 with an extra Y chromosome, referred to as “47,XYY”.

Photo Credit: Prateek Pattanaik/ Creative Commons. Image Description: A simple illustration of a chromosome with centromere, constriction and knob.

This research suggests that one in 500 men has either and extra X or an extra Y chromosome – an incidence twice as high as indicated by previous studies.

Strikingly, of the 213 with an extra X chromosome, only 49 participants (or 23%) knew about it before the study. Of the 143 with an extra Y chromosome, only 1 person was previously aware of it. The vast majority of men in the study with Klinefelter syndrome or 47,XYY had no reason to suspect that they had an extra chromosome.

Klinefelter syndrome is associated with reproductive dysfunction, manifesting for example as late onset of puberty or low testosterone concentration. Someone experiencing these symptoms might seek genetic testing – which could explain the 49 participants in the study who knew about their diagnosis beforehand. In contrast, the vast majority with 47,XYY apparently had no health issues that previously warranted genetic testing, since only one participant was aware of this diagnosis.

When the researchers linked the genetic data with the health history of the participants, they found that the participants with either Klinefelter syndrome or 47,XYY had a higher risk of developing diseases such as type 2 diabetes, venous thrombosis, pulmonary embolism, and chronic obstructive pulmonary disease. However, the researchers note that the incidence of these diseases is partially explained by other risk factors, such as having a higher body mass index, and smoking.

The authors of the study conclude that we need “more genetic tests” when people have fertility difficulties or when they develop conditions like diabetes or clotting problems. Genetic testing could presumably help identify further health risks, or underlying genetic factors contributing to a diagnosis. Having access to genetic information about one’s risk of developing something like type 2 diabetes might be helpful for prevention. So the researchers’ recommendation of genetic testing of sex chromosome differences makes sense. Nonetheless, by making this recommendation, the researchers promote the view that an extra sex chromosome is an underlying abnormality that causes disease.

An alternate conclusion can be drawn from this study. One of the authors states that, “we were surprised at how common this is” to have an extra sex chromosome. Even the diseases linked to the diagnosis of an extra chromosome are fairly common. For example, millions of people have type 2 diabetes. The study shows that having an extra chromosome is more common than previously thought, and that this is pretty normal. Accordingly, the category of “genetically normal” should be acknowledged to be a diverse category.

These findings have ethical implications for another trisomy – Down syndrome, which is caused by an extra 21^st chromosome. This condition is made to seem like a pathology by prenatal testing programs and widespread selective abortion. The medical community has long regarded Down syndrome as a disease, or (like Klinefelter syndrome or 47,XYY) as a risk factor for other diseases.

Meanwhile, many self-advocates and activists in the Down syndrome community argue against this pathological picture of Down syndrome and are in favour of normalization. The Canadian Down Syndrome Society, for example, defines Down syndrome as “a naturally occurring chromosomal arrangement that has always existed and is universal across racial, gender, and socio-economic lines”. According to this perspective, Down syndrome is a part of normal human diversity.

When we find out that many of us are walking around with an undiagnosed extra chromosome, we should be more willing to believe those arguing for the normalization of Down syndrome – another condition caused by an extra chromosome.

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Chris Kaposy is an Associate Professor at the Memorial University Centre for Bioethics, and an editor of the Impact Ethics blog. @ChrisKaposy.