Game of chances: inheritance is a question of probability, not destiny

Charles II Of Spain

We must get over the idea that genes determine – in all but a handful of cases, they simply create minuscule changes in the odds

His nickname was “the Hexed”, and his curse left him childless – probably sterile – along with a suite of disabilities so profound that no single disease can be identified. Charles II was the last of the ruling Spanish Habsburgs, a family that had delivered every holy Roman emperor for 200 years until his death in 1700, and governed a large chunk of mainland Europe during that time. They bore the inimitable Habsburg lip – a prognathous jaw in modern medical parlance – that stuck out literally; a mark of divine power passed from father to son for generations.

But that was precisely the problem. The Habsburg family’s tenacious grip on power meant that they stopped outbreeding more than a century before Charles’s birth. His maternal grandmother was also his paternal aunt, which meant that his paternal great-grandmother was also his maternal grandmother. His family tree is a tragic thicket, and doomed to what is known as “pedigree collapse”.

And so, a 17th-century grasp of genetics ironically undid them. We each have two copies of every gene, one allele – as the variants are known – from each parent. This system means that a good allele hopefully masks a duff one. More than a quarter of Charles’s DNA was identical in both copies, higher than if a brother and sister produced a child, so that dozens of recessive problems were exposed rather than masked. He was cursed by his parents, and their parents, his life hexed by greed.

There is no specific gene for a prognathous jaw. Or the protuberance of a lip. That mark was passed on because the many genetic factors that contribute to a face were shared by the Habsburgs. In a more diluted form, that is why children look like their parents and not like strangers.

I recently had my genome explored by 23andMe, one of many commercial companies that offer a range of services, from ancestry analysis to health. That 50.1% of my DNA is most common in India was the least surprising result. The rest is northern European. That’s what happens when your parents are from India and Scarborough. I don’t flush when I drink alcohol. I have wet earwax. I don’t have the gene for ginger hair. I found this one trivially interesting because my beard is flecked with red among the black (and these days, white) stubble. That simply shows that even for seemingly straightforward traits, the genetics is not. I have brown eyes, which is a trait dominant over blue. Of course, older technology – a mirror – had revealed that to me some time ago. I am not a carrier of an allele that causes a disease that appears in my family, which is of some relief as it greatly reduces the chances of my children suffering from or passing on that disease.

And so on. All these results play into a narrative about inheritance, our idea that our lives are determined by our genes, that the way our lives play out is in the blood – a sticky-out chin, or hair colour, or even behaviour. But we are culturally programmed to misunderstand genetics, from the Habsburg lip, to the way we talk about inheritance.

Here’s a fun game (if you’re a geneticist): Google “scientists discover the gene for” and wander through the headlines returned in their millions. A gene for homosexuality, for political bent, for cocaine addiction, for fear, for what time of day you will die, for spree-killing evil, for happiness, for brain size… For no other reason than utter vanity I propose this fallacy be known as Rutherford’s law: these simplistic narratives are just wrong. Genetics doesn’t work like that; there aren’t really any genes for anything. Some diseases do have a single root cause in a single gene, but how that disorder manifests can be highly variable, a genetics concept called “penetrance”. Inheritance is a game of probability, not of destiny.

It’s not just the headline writers’ fault, though. Science is clearly to blame too. Recall if you will Gregor Mendel and his peas. That 19th-century Moravian scientist monk gave us the rules of inheritance by studying individual characteristics in pea plants. He showed that traits – wrinkly skin, flower colour — are passed on as discrete units, one from each parent, prefiguring the concept of a gene. Through the 20th century we beavered away at the laws of inheritance, and unravelled DNA, and cracked the genetic code. In the 1980s, the first disease genes that we identified were indeed “for” specific diseases, cystic fibrosis, Duchenne muscular dystrophy, Huntington’s disease. But 20 years after these revelations, in the era of the genome, we know these were outliers. We had characterised them first exactly because they run in families in a straightforward way.

Most human traits, behaviours and diseases are complex, with dozens or hundreds of genes playing a small part in concert with the inscrutable milieu in which they operate. So when my personal genome results last week indicated that I have an increased probability of Alzheimer’s, I was not in the slightest bit concerned. It’s not a sentence, or a curse, just a minuscule change in the odds.

We must get over this idea that genes determine. We must look at people as beautifully complex, and diseases as horribly complex. Anyone who says differently is selling something.

Powered by article was written by Adam Rutherford, for The Observer on Sunday 21st June 2015 07.00 Europe/London © Guardian News and Media Limited 2010