In addition to listing all publications that the members of the BSF team have contributed to (see the PubMed links at the bottom of the page), this page highlights publications to which the BSF contributed and which showcase relevant genomics technologies and their utility for addressing a relevant biomedical research question. These research highlights are written by the lead authors of the respective studies and will be updated on a regular basis.

Research Highlights 2013

Somatic mutations of calreticulin in myeloproliferative neoplasms (10 December 2013)

Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schonegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R (published in the New England Journal of Medicine)

A newly identified mutation fills the gap in the molecular pathogenesis of MPN and brings hope to many MPN patients: To date a recently identified mutation in the gene called Janus kinase 2 (JAK2) MPN could be held responsible for MPN in 3/4 of the patients. The remaining patients however did not benefit from this discovery as their MPN was not caused by JAK2 mutations. The research group of Robert Kralovics at CeMM in collaboration with Heinz Gisslinger´s group at the Medical University of Vienna now succeeded in the discovery of a new mutation in the gene encoding calreticulin (CALR). This discovery explains about 75% of the cases for which the reason was unknown so far. It comes to the benefit of millions of patients worldwide as a molecular diagnostic test was made available immediately. The study has been supported by grants from the MPN Research Foundation and the Austrian Academy of Sciences. (read the paper)

A reversible gene trap collection empowers haploid genetics in human cells (26 September 2013)

Bürckstümmer T, Banning C, Hainzl P, Schobesberger R, Kerzendorfer C, Pauler FM, Chen D, Them N, Rebsamen M, Smida M, Cruz FFdl, Lapao A, Liszt M, Eizinger B, Guenzl P, Konopka T, Gapp B, Paparatics K, Maier B, Stöckl J, Fischl W, Salic S, Taba R, Knapp S, Bennett KL, Bock C, Colinge J, Kralovics R, Ammerer G, Casari G, Brummelkamp TR, Superti-Furga G, Nijman SM (published in Nature Methods)

More than 10 years after the first human genome sequence has been published, the vast majority of human genes remain poorly characterized. The major reason is that gene inactivation is notoriously complicated in human cells and therefore, only a handful of human gene knockouts have been established by conventional technology. Recently, gene trap mutagenesis has been applied to a near-haploid human cell line, resulting in complete gene inactivation. Now, a public-private partnership between CeMM and Haplogen has developed this technology further and established an isogenic cell line collection in which each cell line carries a gene trap insertion in one human gene. One important prerequisite for the generation of this collection was a procedure for high throughput mapping of individual clones. To this end, the collaboration with Christoph Bock and the Biomedical Sequencing Facility was instrumental, enabling a pipeline that routinely allowed the characterization of 5,000 gene trap clones in one lane of an Illumina flowcell. (read the paper)

B cell deficiency and severe autoimmunity caused by deficiency of protein kinase C delta (14 January 2013)

Salzer E, Santos-Valente E, Klaver S, Ban SA, Emminger W, Prengemann NK, Garncarz W, Müllauer L, Kain R, Boztug H, Heitger A, Arbeiter K, Eitelberger F, Seidel MG, Holter W, Pollak A, Pickl WF, Förster-Waldl E, Boztug K (published in Blood)

Primary B cell disorders comprise a heterogeneous group of inherited immunodeficiencies, often associated with autoimmunity causing significant morbidity. The underlying genetic etiology remains elusive in the majority of patients. In this study, we investigated a patient from a consanguineous family, suffering from recurrent infections and severe lupus-like autoimmunity. Immunophenotyping revealed progressive decrease of CD19(+) B cells, defective class switch indicated by low numbers of IgM- and IgG-memory B cells as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site mutation in protein C kinase delta (PRKCD), causing absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) was decreased and mRNA levels of nuclear factor interleukin-6 (NF-IL6) and IL6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B cell deficiency with severe autoimmunity. (read the paper)

Publications of the BSF team