Why are Ashkenazi Jews more likely to carry mutations for genetic diseases?
A curious adult from New York asks:
"I am descended from Eastern European Ashkenazi Jews, which are known to be at a much higher risk than all other groups to have genetic mutations for diseases such as Tay Sachs and Cystic Fibrosis. They also have a higher risk than the general population of other diseases such as breast cancer, PCOS and diabetes.
I am extremely curious to find out: what did my ancestors do to develop such gene mutations and diseases? Did marrying close relatives cause it? I doubt it because Sefardi Jews also marry often within family and don’t have any of the above diseases.
Is it possible for the current generation to cure the mutations or at least prevent it from spreading?"
The genetic burden on some groups does seem unfair. You've listed many of the more common genetic problems that affect Ashkenazi Jews.
But other groups have their own problems as well. Extra fingers and toes for some Amish communities (as well as cystic fibrosis and a number of other conditions).1 Severe color blindness for Pingalese Islanders.2 Fanconi anemia for the Afrikaners of South Africa.3 And the list goes on and on.
What do all of these groups have in common? They were all founded by small numbers of people. And members of these groups do not tend to marry outside of their circles. This is all it takes.
The founder effect
The disease genes started out in the group simply because of chance and bad luck. But they stayed because members of the group tended to have children with other members of the same group. No fresh genes were added to the pool to dilute the disease-causing ones.
Let's use Ashkenazi Jews as an example to see how this works. In the first century CE, a group of Jews escaped from Israel to Europe. These folks were the forerunners of all 8 million or so of today's Ashkenazi Jews.
Many members of this small founding group happened to share the same diseases in their DNA. Where did these disease genes come from?
We all have them. Each of us probably carries somewhere between 1 and 4 harmful mutations in our genome.4
But this isn't usually a problem because these disease genes are recessive. And rare.
For our discussion here, recessive just means that to get the disease, you need to get the disease gene from both parents. Because most of these disease genes are rare, this doesn't happen very often. But if a disease gene becomes more common in a population, then the disease will become more common too.
So some disease genes are more common in Ashkenazi Jews than in the general population. Why?
We've already discussed one way -- the founding group happened to have the same deadly diseases in their DNA. Geneticists call this the founder effect.
There are other ways that a disease gene can become more common when the group is small. This is because of something called genetic drift.
Genetic drift and random chance
For example, an accident might have killed off most of the people who didn't carry the same disease genes purely by chance. Now the number of people in this group who share the same disease genes goes up.
Imagine that there are a thousand people, some of whom are carriers and some of whom are not. Lightning strikes one of the carriers. Given the number of people, the lightning strike won't have much of an effect on the number of disease genes in the population.
Now imagine two people, one who is a carrier and one who is not. Lightning strikes the person who isn't a carrier. Within this small group, the disease gene frequency has doubled from 1 in 4 to 1 in 2.
And if lightning strikes the carrier, the disease is wiped out in the group. It is all a matter of chance.
Another way genetic drift might have worked is if the disease genes just happened to be passed down more often. This can and certainly does happen.
Imagine that two carriers get married. The way genetics works, each child has a 1 in 4 chance for not getting the disease gene, a 1 in 2 chance for being a carrier and a 1 in 4 chance for getting the disease.
Note that I said each child has these chances. This does not mean that if someone has four kids, they would automatically have 2 carriers, 1 child with the disease and 1 child free of the disease gene, any more than a couple with 4 kids would automatically have 2 boys and 2 girls. So it is possible for two carriers to have all children who are carriers, or none at all.
Again imagine a thousand people, some of whom are carriers and some of whom are not. One couple has more carriers than might be predicted. Another has fewer. It all evens out in the end because the group is large.
But if we only have two people and all of their children are carriers, then the next generation will have more of the disease gene around. This isn't a large enough group to even things out.
As you can see, in a large population, genetic drift doesn't tend to be a big deal. With a small group, it can easily make disease genes more common.
For these and other reasons, certain disease genes were common early on for Ashkenazi Jews. These genes then stuck around because Ashkenazi Jews tended to marry within the same group.
This practice maintains the genes in the population because members keep trading the same genes back and forth. And so do their descendants. This tends to cement in the percent of people who are carriers for the disease genes.
All of this led to the genetic burden Ashkenazi Jews have to this day. They started out as a small group that shared certain disease genes. Intermarriage kept these genes in the population.
So even as they expanded to the 8 million we see today, genetically they are still very related to that original small founding group. The disease genes have stayed as common as they were at the beginning.
The future of the gene pool
So this is why Ashkenazi Jews tend to get certain diseases more often than other people. Is there anything that can be done about it now?
One approach would be to marry outside of the group. Over time, the disease genes would dilute out and these diseases would happen about as often as they do in the general population.
Of course this may not be an option for cultural and/or religious reasons. Another possibility is to use in vitro fertilization (IVF) for a few generations and select only those fertilized embryos that do not carry the disease.
This approach has obvious ethical dilemmas and would be very expensive as well. The ultimate approach would be to go in and fix the genes. However, the science to do this is still pretty far off.
So for now, carrier and prenatal testing are probably the best bet until science can fix disease-causing genes. The history and culture of the Ashkenazi Jews is a rich and vibrant one. Intermarriage kept their culture from being overwhelmed by the cultures around them. But it also kept certain disease genes more common in their population.
Author: Dr. D. Barry Starr
Barry served as The Tech Geneticist from 2002-2018. He founded Ask-a-Geneticist, answered thousands of questions submitted by people from all around the world, and oversaw and edited all articles published during his tenure. AAG is part of the Stanford at The Tech program, which brings Stanford scientists to The Tech to answer questions for this site, as well as to run science activities with visitors at The Tech Interactive in downtown San Jose.