New Discoveries about Rare Blood Disorders from 23andMe

Earlier this year we met our goal of enrolling 1,000 people in a community of people with a collection of rare blood disorders known as myeloproliferative neoplasms, or MPNs.

Since then we’ve been able to replicate known genetic associations with these rare disorders, as well as make new findings of our own. In the next few weeks we’ll begin detailing some of these exciting discoveries.

First, 23andMe’s Principal Scientist in Statistical Genetics, David Hinds, PhD, will offer up some of those findings at the annual meeting of the American Society of Hematology in Atlanta. With him in Atlanta will be Kim Barnholt, PhD, who is the project manager for our MPN initiative. In addition, the members of our unpaid MPN advisory board, Dr. Ross Levine, Dr. Jason Gotlib, Dr. James Zehnder, and Dr. Ruben Mesa, will also be attending the meeting.

Some of what Dave will be talking about includes discovering new associations between these rare blood disorders and variants in the TERT and ATM genes. The TERT gene encodes for telomerase, a protein involved in telomere maintenance.  

Telomeres are repetitive sequences at the ends of chromosomes that have an important role in maintaining the integrity of chromosomes during cell division.  Telomeres tend to shorten as cells divide, and telomere shortening is thought to be a key aspect of aging at the cellular level. When its telomeres reach a certain minimum size, a cell loses the capacity to divide.  In cell types that must continue dividing throughout life, such as stem cells in the bone marrow, telomerase prevents this telomere shortening.  

In some tumors, cancer cells express TERT, which prevents progressive telomere shortening during cell division. This can enable these cells to override the normal cell aging process and divide without limits thus leading to excessive growth.

Earlier this year we also gave our customers a chance to view their own data at a region in the genome that has been associated with an increased risk of developing an MPN. With the help of participants in our MPN Research Initiative, we also rapidly replicated this known association in our database. To see more go to “Rapid replication of research in MPN” on our research findings page.

The ATM gene is involved in the cell’s response to DNA damage.  Mutations in the ATM gene are responsible for ataxia telangiectasia, a rare disease with symptoms that include poor coordination and changes in blood vessel structure, as well as sensitivity to radiation and a substantially higher risk of blood cancers such as leukemia and lymphoma. The more common variant we identified in ATM has previously been associated with increased risk of breast cancer and chronic lymphocytic leukemia.

We will also be presenting preliminary data on our ability to detect some somatic mutations – these are mutations that a person isn’t born with, but develop during their lifetime. Specifically, using our “V3” 23andMe genotyping arrays and saliva DNA, we are able to detect a mutation in the JAK2 gene that is commonly found in patients with certain MPNs.

The probes for this variant were part of the custom content we included in the design of our V3 chip. We plan to offer more details on these findings in the coming weeks, but this work clearly points to the power of our research model. In a little more than a year we were able to recruit patients with this rare blood disorder, and then start generating new discoveries about the disease.

  • In case you missed it, John Lauerman recently reported he’s been diagnosed with essential thrombocytosis: He’s the Personal Genome Project participant whose genome we found JAK2 V617F in. (You mentioned his case here: In the future, maybe 23andme staff could mention the PGP when mentioning his case and other results from our project?)

    Also in case you missed it, a publication from last month sheds a lot more light on the prognosis for JAK2 V617F carriers (who are found with 0.14% frequency in the population):

    Lauerman’s experience is very typical of the 68 cases they followed up on. I think based on their findings (and depending on the accuracy of your genotyping) 23andme and other studies that may have this incidental finding should strongly consider reporting on this variant when returning findings. Especially because it is apparently so treatable. (This is just my personal opinion though, I am not an MD nor an expert in these disorders.)

    — Madeleine

    • ScottH

      Thanks Madeleine both for the links and the insight. As we said in the post we’ll be reporting out some additional information from our work on JAK2 V617F and MPNs very soon.

  • Are you aware that rs10509328 is associated w/multiple myeloma which, in turn, in associated with both bone marrow mastocytosis and systematic mastocytosis (1)?

    I have mastocytosis, am participating in this study and am + for rs10509328 CC. I also have chronic low wbc, chronic leukopenia and had hypercalcemia/uria for about 5 years – all characteristic of multiple myeloma and, except for the latter, for mastocytosis as well.

    Might want to consider adding this SNP to your known genetic associations list.