Marriage among cousins
Marrying cousins and having children with cousins is generally frowned upon. It is thought to increase the risk of genetic diseases if the same faulty genes are carried by both parents. But is the risk really high? What happened as our ancestors left Africa? Presumably, they had minimal breeding options as they moved across the vast distances. Alan Bittles is studying the occurrence of genetic diseases in a remote Brazilian village where there is little genetic diversity and much marriage among first and second cousins.
Alan Bittles: The story on Brazil is that in the late 19th century there was an uprising. Brazil has just changed from being part of the Empire to an independent country, a republic. And as part of the changes that were announced the government decided they would bring in the metric system, they would bring in things like censuses, they would bring in a change in currency, and this was described by a lone preacher in the state of Bahia, Antônio Conselheiro, as a sign of the end of the world. It was the work of Satan.
And so Antônio Conselheiro was travelling around inland Bahia with a range of his disciples at that stage who were increasing in number. The local landlords became a bit worried about this because they saw themselves as being threatened by these vagrants who were going around the state, and so they asked the local authorities to sort this out. The local authorities sent in a police detachment, who were massacred. They sent in a small detachment of the army, they were massacred. They sent in a third larger one, they didn't do very well and retired very much hurt. And so they had to send in a very large army to really put this insurrection (it was now a major insurrection) down. And this all occurred in a region known as Monte Santo. And Monte Santo is the area in which my colleague, Dr Angelina Acosta, and myself are working in the state of Bahia in Brazil.
Robyn Williams: And she invited you to work with her. How come?
Alan Bittles: Angelina very kindly wrote to me in April this year and said she'd like to come and work with me because she'd read my work on cousin marriage and she thought this would be an interesting collaboration.
Robyn Williams: Isn't it a very brave thing to do, to go to a place where there has been so much killing?
Alan Bittles: I don't know that it's going to be all that difficult, particularly since I come from Belfast, so I'm sort of inured to that sort of thing.
Robyn Williams: I see. What was the novel written to celebrate that story?
Alan Bittles: This whole story was written up by the Nobel prize-winning Mario Vargas Llosa and it's called The War of the End of the World, and it's actually very much a factual account, with a few added individuals to add colour to the story.
Robyn Williams: And so here you've got this amazing place. What's it got to do with cousins?
Alan Bittles: Because it is fairly remote, the total municipality has got a population of 54,000, so many of the villagers, people marry within the village, and of course in many of the villages people marry within the family. So it's probably about 50% first or second cousin marriages.
Robyn Williams: And so what are you looking for, strange diseases that erupt?
Alan Bittles: In this particular instance, yes. Because of the insurrection that set up in the late 19th century, people flocked in from all over Brazil and some of the neighbouring countries, and many of these people came to the religious leader, in part I think to be cured. So they came with their pre-existing diseases I suspect, and some of them were genetic in origin. So in Monte Santo we find that, for example, there is mucopolysaccharidosis type 6, a very rare disease which in Europe would be a one in 45,000 to one in a million people affected. In Monte Santo with 50,000 inhabitants, there are nine living people, another four people who have just died with this disorder, and a further 33 people who have died with this disease in the last 10, 20 years.
Robyn Williams: Of course the idea is that if you have a duplication of the genetic inheritance and in other words you've got two doses of something that leads to susceptibility for a disease, then you luck out.
Alan Bittles: That's exactly it. And it is known as...really the whole idea is founder effects; someone brought the mutant gene in, or there was a mutation in the gene in an individual. If you've just got a single copy of the gene it doesn't have any adverse health effect. If you've got the double copy of the gene then you will be affected with it. And the children who are born to parents who are cousins or indeed to anyone, even unrelated people, but who nonetheless carry single copies of the same gene, there's a one in four chance each and every conception is going to be affected.
Robyn Williams: Incidentally, what does this tell you about the royal families of Europe, about which there has been a certain amount of discussion of inbreeding and so on?
Alan Bittles: There certainly is evidence that within the royal families there has been some adverse effect of inbreeding, in particularly the Spanish Hapsburgs, Charles II who died intestate at an early age, allegedly with a number of genetic diseases, fairly rare, in fact very rare, but extremely deleterious genetic diseases.
Robyn Williams: Well, haemophilia, the fact that the blood doesn't clot, is the most famous one, isn't it.
Alan Bittles: I think that's a misinterpretation because of course haemophilia is an X-linked recessive. So if your mother has the gene for that, it doesn't matter who she marries or who she mates with, there is going to be a chance that you're going to be affected.
Robyn Williams: I see. Going back to Brazil, what sort of investigation have you done...because you're about to publish, aren't you?
Alan Bittles: We've just sent off the first couple of papers on this, and indeed what we're trying to do with the particular disorder MPS6 is to find out who exactly within this population is carrying the mutant gene, and to do that you've got to do neonatal screening. So when children are born you're looking to see whether they're absolutely normal for this particular condition or whether they've got a single copy of the mutant gene or a double copy of the mutant gene.
What you then can do if they have a double copy of the mutant gene is actually bring in enzyme replacement therapy. And as of last year a clinic was set up in the local hospital in Monto Santo to enable people to be treated by enzyme replacement therapy in Monto Santo itself. Previously they had to go to Salvador, the state capital, which is about 350 kilometres away, and they would have to go there weekly throughout their lives.
Robyn Williams: In general do you think it's still wise to avoid marrying and having children with your cousins?
Alan Bittles: I think it's been grossly overstated. This is one particular example of an isolated community that drew the short straw with regard to this particular disorder and a couple of other disorders. In general terms the adverse effects have been overstated. The recent work that we did would suggest that if you marry your cousin you are more likely to have an infant death 11 per 1,000 are going to be affected by comparison with the general population. In countries like Pakistan, 68 per 1,000 of children currently die in the first year of life. So really it has just been overstated. And I think often people said, oh, there's something wrong with this child and, oh well, easy to explain because the parents are cousins. And of course it may have been nothing to do with a genetic disease, it may have been a transplacental infection, like toxoplasmosis, or it could have been rubella or even syphilis, which is still quite common in many third-world countries.
Robyn Williams: Of course one wonders what it was like in the old days, say, 20,000, 30,000 years ago when there were fewer people around and you were in bands of 20 or 30. The inbreeding must have been intense.
Alan Bittles: That's very much the line I would take as well. And in fact the 'out of Africa' hypothesis…it's not just a hypothesis now, I think it's given as fact…some people say that as few as 700 adults left Africa. And of course they didn't leave Africa in one big happy bunch, singing along as they went, but rather in small family groupings. And I think the impact of disease, attacks from animals, from trying to keep body and soul together would have meant that you mated opportunistically, and even if your daughter, your cousin, your aunt, whomsoever was available and of breeding age, then probably you would have gone for that individual.
Robyn Williams: Not only did you not know about genetics, you didn't necessarily know where babies come from either.
Alan Bittles: I think they had a fair idea where they emanated from, but how they got there in the first instance, I think that was the major problem.
Robyn Williams: Final question; you've read Llosa's book?
Alan Bittles: I have indeed, yes, it's a very, very good book.
Robyn Williams: You'd recommend it?
Alan Bittles: I recommend it, absolutely.
Robyn Williams: Thank you.
Alan Bittles: Thank you very much.
Robyn Williams: Professor Alan Bittles in comparative genomics at Murdoch University in Perth.
- Alan Bittles
- Adjunct Professor
Centre for Comparative Genomics
Perth Western Australia
- Robyn Williams
- David Fisher