Stories and Examples

Examples

Linda

After being diagnosed with breast cancer, Linda did genetic testing and was told that she had a pathogenic mutation in the BRCA1 gene. When Linda was told that she had inherited the variant from one of her parents, she suspected it was from her late mother, who had been diagnosed with breast cancer in her 70’s. Linda decided that she wanted to try to trace back where she had gotten the mutation from in order to see who else could have it and who could be at risk.

But when Linda asked her family members on her mother’s side of the family about any genetic testing or cancer diagnoses, there were no other family members who had been diagnosed with cancer. She thought that she had hit a dead end with asking those relatives, so she decided to try to also research her father’s side of the family, even though she was more skeptical because he was male and did not have breast cancer. When she spoke to her father about it, he told her that he thought his mother had been treated for early breast cancer in her 50s. Linda’s father did not know much about it because he had moved away by that time, and his mother was very private about her health. Linda knew that her grandmother had died of a heart attack in her 60s, but did not know about the breast cancer story.

When Linda asked her father about any other cancer diagnoses in his family, he told her that his first cousin, Sara, was recently diagnosed with ovarian cancer. Linda was able to get in touch with Sara with help from her dad. Linda had recently had genetic testing because of her ovarian cancer. When Linda and Sara compared results, they found that they both had the same variant in BRCA1, meaning that Linda had inherited her mutation from her father.

Sara must have inherited it from her mother, who was related to Linda’s paternal grandmother. Linda and Sara started to go through their family trees to find out which relatives they had in common. They were linked through Sara’s maternal grandparents and Linda’s paternal great-grandparents, Richard and Mary-Ann. One of those two had the variant, but they could not tell which one.

Linda decided that she wanted to look for more distant relatives who had her variant. She found Connect.MyVariant. Based on the information, she decided to create a forum for her variant on the American Cancer Society’s Cancer Survivor network. She added this forum to the Connect.MyVariant forum list. She also emailed the Connect.MyVariant team and they told her how to find the genomic location of her variant (chr17).

Linda told Sara that she was looking into finding more distant relatives who might have their variant. She said that she was thinking doing a commercial DNA test, in order to help her find out more about who she might be distantly related to, which could help her investigation. Sara encouraged Linda to the Ancestry DNA test because she herself had done it a few years ago, out of curiosity, as part of her family history hobby. Sara had found out about many of her genetic relatives, and she wanted to see how much Linda was connected through their DNA. Linda and Sara immediately connected their family history trees on the Ancestry website, because they already knew about their connection through Mary-Ann and Richard.

Linda kept on browsing the ConnecyMyVariant website, and she saw that you could find more genetic relatives with DNA. After Linda sent the DNA saliva kit back and received an email about her results, she could see that she and Sarah were indeed related, and shared 318 cM across 18 segments of DNA. Linda wanted to see which DNA segments she shared with Sara. She knew that she shared the segment on chromosome 17 with Sara, because that is where she had learned BRCA1 is. Linda wanted to see if she could find anyone else that shared the same segment of chromosome 17 DNA. Even though the Ancestry DNA testing results provided a list of shared matches between Sara and Linda, they did not provide enough information to figure out who shared that specific segment on chromosome 17. To figure this Linda went to GEDmatch.com. Linda downloaded her raw DNA information from the DNA ancestry testing company website and uploaded it to GEDmatch. She also asked Sara for permission to put Sara’s DNA results on GEDmatch too, since she wanted to find out who had the same chromosome 17 segment as both of them. Sara agreed, and Linda uploaded both of their DNA results onto GEDmatch.

Linda used the “Matching Segment Search” tool to find relatives that shared the same segment on chromosome 17 where BRCA1 was with her. She found 4 people who did. One of them was Sara. She knew that about half of these people would have the BRCA1 copy she inherited from her mother, but she knew that she wanted to find the people with the BRCA1 copy with the pathogenic variant, which she inherited from her father. Since Sara also had this BRCA1 copy, Linda did the “Matching Segment Search” using Sara’s GEDmatch number. She saw 6 people, including herself, who shared the chromosome 17 segment with Sara.

In the end, Linda found 2 distant relatives that she did not know about before who shared chromosome 17 segments with both her and Sara. These two people may have inherited the same genetic variant. Since these users had provided their email addresses on GEDmatch, Linda was able to contact them. These two people were siblings, Marc and Shauna, who had uploaded their data to GEDmatch after they had done 23andMe. Linda shared her story about her pathogenic variant, and also encouraged Marc and Shauna to get clinical genetic testing because they may also have inherited the same variant from a common ancestor. Marc, said that he was not interested in genetic testing at that time but would think about it in the future, especially if it might be relevant for his young daughters. Shauna said she wanted to get tested as soon as possible because she felt that her cancer risk would be high, being a woman in her 30’s. She knew that her maternal grandmother died in her late 60s of ovarian cancer, and wondered if it could have been because of BRCA1.

Shauna found a genetic counselor near where she lived and contacted her to make an appointment to discuss getting genetic testing and learn more about her risk for cancer.

Mary

Mary recently got genetic testing after receiving a diagnosis of breast cancer. Her testing showed that she had a pathogenic variant in the BRCA2 gene, which means that genetic variant caused her breast cancer.

Mary wanted to know if any of her relatives had this variant too. She knew that her children, sisters, and brothers all had a 50% chance of having the same variant, but she was curious about her first cousin, who had breast cancer a few years earlier. This cousin’s mother, Mary’s maternal aunt, had died of ovarian cancer several years ago.

Mary talked to her cousin at a family dinner, and her cousin told her that she had a genetic variant in BRCA2 identified through genetic testing. When Mary and her cousin compared their genetic testing results, they found out they had the same pathogenic variant in BRCA2. By connecting the lines through the family tree, Mary and her cousin figured out that both of their mothers also had the BRCA2 variant. The variant probably caused the ovarian cancer in Mary’s aunt.

Mary began to wonder if might be able to find other, more distant relatives with the BRCA2 variant. These relatives might have an increased risk for getting breast and ovarian cancer. Mary bought an ancestry testing kit. When she looked at her results, she saw that the ancestry testing company had listed three individuals who had also gotten tested and were found to be related to her. Some of these individuals had listed their contact information, too.

Mary reached out to these distant relatives and explained she had a pathogenic BRCA2 variant which caused her to get breast cancer. She asked if they would be interested in getting tested for the same variant, because if they knew they had the variant, they could start getting preventive measures like screening and help their close relatives get tested too.

Inspired by her earlier discovery with her first cousin, Mary also asked these relatives if they might be interested in connecting their family trees with her own. She explained that by laying out exactly how they were related to each other, they might be able to identify relatives “in between” who might have the variant and be at risk for cancer.

Two relatives responded to Mary through the ancestry testing site. One was a woman who already got genetic testing because she had breast cancer at a later age than Mary. This relative had the same variant in BRCA2, which Mary confirmed by exchanging genetic test reports with her. Mary began to work with this relative on connecting their family trees. It turned out that the relative and Mary were third cousins: they shared a great-great-grandmother on Mary’s mother’s side and the relative’s father’s side. Mary and the relative contacted the connecting relatives that they knew tell them about the variant and help them get testing. When they got stuck, they used other public resources to find and contact relatives that they had not met personally

The other relative who responded to Mary was a man had never had cancer or genetic testing. He was worried about the cancer risk for his daughters. This man had been adopted as a baby and did not know a lot about his family history. He was excited about the possibility of getting more information about his family’s health history. Mary sent this man her genetic testing report with the variant. She sent him information about seeing a genetic counselor so that he could get tested.

Tom

Tom got diagnosed with Lynch syndrome after finding out he had a likely pathogenic variant in the MSH2 gene. Tom’s parents had died in their 40’s in a car accident. Tom’s brother had died of colon cancer in his 40’s. His paternal aunt, who had raised him and his brother, had endometrial cancer in her 60’s. She also had the same variant.

Tom had already been getting regular colonoscopies because of his brother’s diagnosis, but he wanted to help others who might have a cancer risk due to this variant. He looked at the connectmyvariant index for his variant, and did not find it listed. His online search for his specific variant confirmed that there were no postings. He decided to make his own forum, where Tom shared his experience with genetic counseling and preventive colonoscopies.

One day on the forum, someone posted an interesting article about genetics. The article suggested that people with the same rare genetic variant, such as this one, might all be descended from a common ancestor. This meant that everyone with the variant, such as the members of the message board, might be related to each other in some way.

Tom was interested in seeing how he might be related to other members of the message board. He used online software to create a family tree with the names, birth dates, and death dates of the relatives that he knew about. He asked his aunt for help filling out information about his grandparents, great-grandparents, and other ancestors. Tom then used private messaging to share this family tree with two other members of the message board, who had also expressed interest in linking up their families.

Tom and one member of the message board were able to do some digging and found out that they were second cousins once removed. Specifically, Tom’s grandmother was the sister of the other member’s great-grandfather. Tom’s grandmother had lost touch with her family after moving across the country with her husband. Tom and his cousin each got in touch with their connecting family members who were still living and told them about the genetic variant and how to get tested for it.

Tom did not have as much success with the other member of the message board. While this member shared a surname with Tom, which they used to look up historical records, the closest they got was finding out that they each had ancestors who had settled in the same region in the 1800s. They were not sure how those ancestors were related to each other. Tom was a little disappointed, but he still found it a fun exercise in learning genealogy. Tom and this other member agreed to update each other if they found any more information in the future.