Saturday 6 December 2014


When I read the reports about genetic predisposition to violent crime, it made me think of a parallel ethical and genetic fuss that we had wash over us back in the 1960s and 1970s. The recent Swedish study concentrates on a statistically significant excess of one variant of 2 or 3 genes among violent offenders who had been tested in prison. Fifty years ago, the finding was that extra whole chromosomes appeared to be more prevalent among a similar population. In order to set the scene for an investigation of people inheriting a wonk number of chromosomes, I uncovered an interesting tie in between aneuploidy (as we call any count of human chromosomes that is different from strictly normal 2N=46) and a variety of medical conditions, some fatal, many severely debilitating. There I suggested that the problem was in disrupting gene "dosage".
it's true that having extra copies of chromosomes can increase the activity of the genes that are tied up in those strings of DNA,
our health, happiness and correct development hinges on having this gene "expression" in a rather delicate balance
surely it's a problem if women have two copies of the X chromosome while men only have one X (and a diminutive Y with 4 handfuls of genes).  And it would be, but for the fact that, early on in development of all mammals, one of each pair of X chromosomes is switched off.  This rather radical solution to a universal developmental problem was discovered by a British geneticist called Mary Lyon and published in 1961. The inactivated X stains darker than the rest of the genome and can be seen down the microscope as a blob attached to the inside edge of the nucleus [R above]. It should be obvious that women should have a single Barr body on suitably stained cells and men should have none and that's true . . . except when it isn't.

X0. Somewhere around 1 in every 2000-5000 girls born doesn't have a Barr body no matter how hard you look.  That's because they are missing one of their X chromosomes entirely, a syndrome that was recognised by British endocrinologist Henry Turner in 1938 a generation before we even knew how many chromosomes we had.  He cued in on the fact that these girls show a suite of problems starting with dysfunctional ovaries which means no periods, no ovulation and no children. Diabetes, heart and thyroid problems are also common. I'll put on my skeptic hat to pass on claims abroad that Turner's girls are not-so-good at mathematics and visual-spatial problems.

XXY. The mirror of Turner's syndrome is Kleinfelter's which was first thought through and described by Klinefelter, Reifenstein & Albright from Mass General Hospital in Boston (1942). You'd think that such chaps would be hormonally conflicted, being both XY and XX and they are, up to a point.  XXYs definitely have a Barr body and tend to have rather smaller testes and rather bigger breasts than are normal in men, but many go through their whole lives without a medical diagnosis. Although Bob's hypothesis is that they suffer from more than their share of having their heads flushed down toilets in school which is also known as psycho-social problems in adolescence. 1 or 2 cases are found per 1000 males in pretty much all ethnic groups which have been investigated but if you tilt the playing field and only look at infertile males then the rate is about 30 per 1000. The chromosomal evidence for both Turner's and Kleinfelter's syndromes was established by counting in the late 1950s just before Mary Lyon published her study of Barr bodies.  The Albright who co-authored Kleinfelter's paper also polished and extended the description of Turner's syndrome, so that is sometimes called Morgagni-Turner-Albright syndrome to acknowledge this.

All imaginable variants on this theme have now been identified to join X0 and XXY - XXX, XYY, XXXY, XXXXY and XXYY have all been found in people albeit with extreme rarity.  Some genes, for colour blindness for example, are carried on the X chromosome.  In cats a coat colour mutant called Orange is inherited in this manner and if a kitten inherits an orange gene from one parent and the regular variant from the other then a tortoiseshell or calico cat results.  This shows [R above] that the inactivation of the X chromosome is random: in some skin cells the black gene is switched off in others the orange is inactivated. This is the explanation for the folk truism that all tortie-cats are female, which true unless tort-he has an extra X chromosome. You have my permission to bet long on such cats having small testes, and a Barr body, but it's up to you to lift his tail and prod.


  1. so whats the difference between turner's syndrome where you only have one existing X chromosome and healthy women with one active X chromosome?

    1. That's a damned good question. I'm glad someone is awake out there. The deal seems to be that X-inactivation is not a black&white issue, only 75% of the 'inactive' chr is actually switched off, and the other genes presumably have function in fertility and the other correlates of Turner's: diabetes, heart & neck devt, spatial skills etc. If anyone tells you they understand how genes interact to achieve normal development, you shd raise an eyebrow under your skeptical hat.

    2. normal Women have two active X-ch, only the individual cell has one active X-ch. The Turner women, that can also be a man in the sense its a fragile Y-ch. Turner is complex sets of cases when you look at the details.