By Monica Heger
SHENZHEN, China — BGI and Sweden's Karolinska Institute University Hospital plan to develop an immunogenetics center based in BGI's hometown.
As part of the plan, the institutes aim over the next five years to sequence the major histocompatibility complex regions of 100,000 patients — including both healthy controls and those with immune diseases — as well as the exomes, regulatory regions, and population-specific SNPs of a large number of those patients in order to better understand immune disease.
The partnership was announced here this week at the International Conference on Genomics hosted by BGI.
Lennart Hammarstöm, a professor of clinical immunology at the Karolinska Institute University Hospital, Huddinge, who will head up the new division, told Clinical Sequencing News that the goal will be to figure out the genetic underpinnings of immune diseases.
While 1,800 genes are known to be related to the immune system, so far only 200 of them have been linked to disease. "We've only scratched the surface of diseases associated with the immune system," he said. Of the known diseases that have been linked to disease, most of them are simple, monogenic diseases, he said.
Details of the project are still being worked out, said Hammarstöm, but it builds on years of collaboration between his group and BGI.
BGI will perform the sequencing and bioinformatics analysis. Hammarstöm said the researchers will use a targeted sequencing approach that captures not only the MHC region, but also the exome, regulatory regions, and population-specific SNPs. Researchers at BGI have been developing a capture technique dubbed All-in-One, which targets those regions (IS 11/29/2011).
The All-in-One capture technique will be the "golden middle road" between whole-genome sequencing, which is still cost prohibitive for thousands of samples, and exome sequencing, which does not capture enough of the genome, said Hammarstöm.
A large portion of the analysis will focus on the HLA region, because it has been associated with many autoimmune and immunodeficiency diseases. Because of this, a large patient population is critical because there is so much variability within the HLA region between individuals, so distinguishing disease-causing variations from normal variation is difficult. Even when sequencing HLA-homozygous individuals, "there can be around 5,000 differences" between them, he said.
Hammarstöm, in collaboration with BGI, has already begun using exome sequencing in a pilot to study the genetics of common variable immunodeficiency, a group of immunodeficiency diseases with similar symptoms but different underlying causes. There are seven known genes linked to CVID, but those explain only five to 10 percent of its heritability, he said.
At this week's conference, he presented preliminary data from the pilot, where exome sequencing identified a novel, potential CVID gene that has been previously linked to immune activation.
Hammarstöm plans over the next year to build a consortium of experts in the field of immunodeficiency and autoimmune diseases. Samples will come from those collaborators as well as from biobanks, such as Europe's biobank of patients with immunodeficiency diseases.
Hammarstöm said that the team would have a protocol in place for returning medically relevant genomic information to physicians, who could then inform their patients.
The consent process is still being worked out, said Hammarstöm."There's a need for an ethical discussion about what [these] new genetic studies will bring," he added.
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