But what are the chances you actually share a common ancestor?
Imagine that the DNA of a gene mutated in a certain way just once in history. The mutation would create a new variant of the gene. At first, the variant would exist in only one person’s body. But that person might pass on copies of the variant to their children. And those children might pass on copies, too, until the variant exists in many people’s bodies. Still, the only way to get a copy of that unique variant would be to inherit it from someone who already had it. All people with that variant must have inherited it from the first person to have the mutation. That person is the “founder” of the variant.
But, in reality, the same mutation can happen more than once. There is more than one way to get a copy of a variant. A person could inherit it, or an identical mistake could happen in their body, called a de novo mutation.
Each time a de novo mutation occurs, an additional founder could be created. And every founder has their own line of descendants. If you meet someone with the same variant, you might descend from the same founder. Or you might descend from a different founder with no relation.
What are the odds you’re from the same line? Dr. Brian Shirts asked this question while studying patients with Lynch syndrome, a condition associated with a higher risk of colon and other cancers. During the study, Shirts and the other researchers looked at mutations in genes that can cause Lynch syndrome. But they also looked at stretches of DNA around those mutations.
If patients were related, all the DNA—the mutation plus the surrounding areas of the gene—would match. This is because every person has harmless variants throughout the gene where spots of DNA mutated in previous generations. Not everyone has a unique mix of these benign variants. Instead, for a given gene, a population might have 10 or 20 common patterns of these variants. Children usually inherit the variants in a pattern as a group. When someone has a disease-causing mutation, it exists on a background of the harmless variants. The mutation will be inherited with the group.
But if patients were unrelated, the DNA around the mutation would not match. A harmful mutation could randomly happen for a founder with any of these background patterns. If the same mutation happens by chance again, the new founder probably wouldn’t have the same pattern. That would be like a 20-sided die rolling the same number twice in a row.
For groups who shared Lynch syndrome variants, the researchers found that the background pattern of DNA was similar in 90% of cases.
“This isn’t absolute proof that it came from a common ancestor,” Shirts said, “but it’s pretty strong evidence.”
Since 90% of people with a matching Lynch syndrome variant are probably related, you may wonder about people with your variant.
Four clues show if your chances could be that high.
1. You find ancestors who lived in the same area.
Historically, children have tended to settle close to their parents’ home. Over the generations, the family’s footprint gradually spreads out as descendants migrate away. However, a core group usually remains in that origin region.
The map of where a variant occurs may follow the same pattern. Many variants are most common in one place and spread from there. One TP53 variant, c.1010G>A (p.R337H), occurs mostly in Brazil. A CHK2NA variant, c.146T>C (p.Ile49Thr), is associated with northern Mexico. Researchers assume that a variant like this must have started with a single founder who lived in the area where it is most common. Occasionally researchers can name the founder. More often, they can only identify the region. Hundreds of variants have been linked to a specific place.
If you meet someone else with your variant, compare your family trees. Did your ancestors live in the same region? The smaller that region, the more likely that your variant came from the same person. If you both had ancestors from Europe, there’s a chance. But if you both have ancestors from Sicily, there’s a bigger chance.
If you can’t find ancestors from the same region, you may have inherited your variant from different founders.
A variant known as BRCA1 c.68_69del is the most common pathogenic variant of the BRCA1 gene in the world. It is common in part because it happened at least twice. The variant is often diagnosed in people with Ashkenazi Jewish ancestry. It’s also found frequently in India, apparently from a separate founder. If you inherited this variant from Ashkenazi ancestors, you’re probably not related to someone from India with this variant.
2. Your mutation is not at a mutational hot spot.
When a sidewalk has a crooked step or a root blocking the way, several people will trip in that exact spot. Like uneven ground, DNA isn’t uniform. The machinery that copies DNA moves along an irregular path. Some areas of the DNA are more likely to disrupt the machinery’s process. In these “hot spots,” the same mutations have happened multiple times in history.
One of these hot spots occurs in the MSH2 gene, which is associated with Lynch syndrome. In Shirts’s research, multiple people had the variant MSH2 c.942+3A>T—but the DNA around the mutation was mismatched. They were not related. It appears that this particular mutation has happened many times.
Ask ConnectMyVariant staff whether your mutation could be in a hot spot. If so, others with your variant may or may not have inherited it from the same ancestor.
3. Your variant is rare.
If your variant is extremely rare, it is less likely to be at a hot spot or to have multiple founders. It’s possible that everyone with the variant does descend from one person.
4. Your variant does not limit having children.
Some variants lead to diseases that can affect the number of children a founder has. These diseases might have symptoms that are severe or appear early in life. When founders have few or no children, their family trees are small. Their variants do not spread widely each time they occur.
Mutations in the LMNA gene are associated with heart disease and muscular dystrophy. Some of these mutations are more severe than others. Before modern medical treatment, founders with variants that caused severe disease had fewer children. Because their family trees are smaller, it’s less likely that two people with the same variant are part of the same tree.
If you meet someone with your variant, consider whether the variant causes symptoms before adulthood. If not, there’s a higher chance you descend from a common ancestor.
Looking for a common ancestor can change the way you think about inherited disease.
Many people with a pathogenic variant tell their parents, siblings and children about genetic testing. But when you realize how far the variant might spread, you see how many people could be at risk. You could be inspired to tell your aunts, uncles and cousins.
“If you can find a common ancestor,” Shirts said, “then you know which parent, grandparent and great-grandparent it came from. And every descendant of that great-grandparent—all of your second cousins—have greater than 10% risk and should probably be tested.”
Even if you don’t find a common ancestor, your variant matches can be there for you as you make health care decisions. For example, ConnectMyVariant members who inherited the same LMNA variant from different founders have met virtually to support each other. Read about their meet-up in the ConnectMyVariant December 2025 newsletter.
Most research on common ancestors has focused on variants related to cancer risk. However, the same concepts seem to be true for other diseases that are inherited in a similar way.
Is your variant group interested in tracing your family trees? The BYU Center for Family History and Genealogy can help with research. Read more about the process in the ConnectMyVariant July 2025 newsletter.
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