A Sinister Side to Sequencing

As a youngster I naturally imbibed everything I was taught about sex. By the time I emerged from the British university system this amounted to precisely two things: babies come from ladies and there is a really exciting moment just after one pops out when somebody says “It’s a boy!” or, as a variant, “Congratulations Mrs. Miggins, you have a lovely daughter!”


Many years and a career in science later, I now know a little more including the fact that out of every 100 babies born one will have an error in their genetic material that will give rise to a disease. There are more than 3,000 of these diseases, each caused by mutation of a single gene. For some only one of the two copies of a gene need be mutated: for others both copies must be abnormal for the disease to show itself, an example of the latter being cystic fibrosis that occurs in 1 in 2,000 of live births.

Many of these conditions are life threatening and those who have followed my recent eulogies about the wonders of DNA sequencing might have thought that a bit of its fire-power might be turned in their direction. Well, now it has been by a combination of several of the leading genetic disease groups in the USA. Their approach uses the fact that floating in the blood of pregnant women is a significant amount of DNA that has come from her developing baby. This can be easily isolated from a small blood sample (so the procedure is ‘non-invasive’). Repeated sequencing is then used to compare the entire DNA code from junior with that of both his Mum and Dad. This is essential to obtain the accuracy required for reliable detection of mutations carried by the fetus.

Hitherto it has been possible to detect conditions such as Down syndrome because that arises from a gross abnormality – an extra copy of an entire chromosome. However, this work means it is now feasible to do comprehensive, non-invasive, prenatal screening for all genetic disorders. The methods need to be refined and the cost lowered before this becomes generally available but you can be sure this will happen sooner rather than later. A by-product will, of course, be an accounting of X and Y chromosomes, but the suspense of that unknown has been long banished from delivery rooms with the coming ultrasound scans. It might also be noted that inherited mutations in major ‘cancer genes’ would also be picked up – though they contribute only about 10% of cancers.

Whilst this is yet another remarkable scientific advance that in due course will affect many lives, it comes with some serious strings attached. Knowing that an infant will be born with a given defect will mean that the best way of dealing with the condition can be planned in advance. However, it also means that parents may opt not to have afflicted children. This presents serious social and legal challenges that will be magnified if we begin to define genetic variants that associate with, say, intelligence, ball skills or whatever.

For neither the first nor the last time, the wonders of science present mankind with both riches and conundrums.


Kitzman, J.O., Snyder, M.W., Ventura, M., Lewis, A.P., Qiu, R., Simmons, L.E., Gammill, H.S., Rubens, C.E., Santillan, D.A., Murray, J.C., Tabor, H.K., Bamshad, M.J., Eichler, E.E. and Shendure, J. (2012). Noninvasive Whole-Genome Sequencing of a Human Fetus. Sci Transl Med 4, 137ra76 (2012); DOI: 10.1126/scitranslmed.3004323