Story Summary: When the gene, called UGT2B17, is missing from the donors genome but present in the recipients, transplants have a significantly greater risk of a serious side-effect known as graft-versus-host disease, in which immune cells from the donor attack tissues in the recipient. This finding gives us a glimpse into the genetic incompatibilities that can complicate transplants, said first author Steven McCarroll, an assistant professor at Harvard Medical School and an associate member of the Broad Institute of MIT and Harvard, who led the study while working as a postdoctoral fellow with David Altshuler at Massachusetts General Hospital and the Broad. GVHD is a common yet serious complication of bone marrow transplantation (also known as hematopoietic stem cell transplantation), a procedure in which blood and immune stem cells are isolated from a healthy persons marrow and transferred to a patient with a life-threatening disease, often cancers of the blood or immune system. The fact that these deletions are fairly common in human populations suggests that they have been around for tens of thousands of years, and that the encoded genes were not critical to our ancestors. We asked, Are there situations in which these deleted genes might matter more to us than to our ancestors, said McCarroll. One thing that is part of our world that wasnt part of theirs is transplantation. In exploring this idea, McCarroll teamed up with James Bradner, then a postdoctoral fellow at the Broad Institute, who is now an instructor in medicine at the Dana-Farber Cancer Institute and a Broad Institute associate member. It seemed plausible that gene deletions elsewhere in the genome could produce a similar consequence. To investigate this question, McCarroll and his colleagues analyzed a set of commonly deleted genes in roughly 1,300 donor-recipient pairs who were HLA-identical siblings. These samples are part of collections maintained by researchers at Helsinki University, Dana-Farber Cancer Institute, Fred Hutchinson Cancer Research Center, and other institutions. There is a handful of places where physician-scientists had the vision to collect these DNA samples over a long period of time, said McCarroll. The DNA analyses zeroed in on a particular gene called UGT2B17. At one hospital, the odds of developing the disease were about 1 in 6 among HLA-identical siblings without the gene mismatch, but were about 2 in 5 — a roughly 2. In general, the longer a protein, the more opportunities for the immune system to see it….Read the Full Story

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