Featured Publications

Featured Publication

De novo mutations in schizophrenia implicate synaptic networks


Researchers used whole-exome sequencing to study de novo mutations in 623 schizophrenia trios. They found that small de novo mutations were abundant among proteins involved in synaptic and post-synaptic activities. The identified schizophrenia-associated variants are also common to intellectual disability and autism spectrum disorders, suggesting a common etiological mechanism.

Read more at PubMed »

 
 
De novo mutations in schizophrenia implicate synaptic networks
 
 
NGS to determine HLA class II genotypes in hematopoietic cell transplant patients and donors
 
 
Response and acquired resistance to everolimus in anaplastic thyroid cancer
 
 
Exome and targeted sequencing of gallbladder carcinoma identifies ErbB pathway mutations
 
 

De novo mutations in schizophrenia implicate synaptic networks

Researchers used whole-exome sequencing to study de novo mutations in 623 schizophrenia trios. They found that small de novo mutations were abundant among proteins involved in synaptic and post-synaptic activities. The identified schizophrenia-associated variants are also common to intellectual disability and autism spectrum disorders, suggesting a common etiological mechanism.

Read more at PubMed »

Fromer M, Pocklington AJ, Kavanagh DH, et al. De novo mutations in schizophrenia implicate synaptic networks - Nature

Next generation sequencing to determine HLA class II genotypes in a cohort of hematopoietic cell transplant patients and donors

Current human leukocyte antigen (HLA) typing technologies used to match transplant donors and recipients often produce ambiguous results, requiring additional testing. To overcome these challenges, researchers applied multiplexed amplicon sequencing with the MiSeq System for HLA typing. In-phase sequencing of multiple exons from many individuals eliminated heterozygote ambiguities while conserving time and resources compared to other methods.

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Smith AG, Pyo CW, Nelson W, et al. Next generation sequencing to determine HLA class II genotypes in a cohort of hematopoietic cell transplant patients and donors - Human Immunology

Response and acquired resistance to everolimus in anaplastic thyroid cancer

Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective for treating tumors with mTOR pathway alterations. Whole-exome sequencing of everolimus-resistant anaplastic thyroid carcinoma samples revealed mutations in TSC2 and MTOR, which affect mTOR regulation and inhibition. These insights into therapeutic resistance might inform future treatment selection.

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Wagle N, Grabiner BC, Van Allen EM, et al. Response and acquired resistance to everolimus in anaplastic thyroid cancer - New England Journal of Medicine

Synthetic lethality in ATM-deficient RAD50-mutant tumors underlies outlier response to cancer therapy

Whole-genome tumor/normal sequencing of an irinotecan-responsive metastatic small-cell cancer sample revealed a clonal hemizygous mutation in the RAD50 gene. Results indicate that this mutation likely contributed to treatment sensitivity. These findings suggest that a tumor-specific combination therapy strategy might be effective in certain small-cell cancer cases.

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Al-Ahmadie H, Iyer G, Hohl M, et al. Synthetic lethality in ATM-deficient RAD50-mutant tumors underlies outlier response to cancer therapy - Cancer Discovery

Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency

Common variable immunodeficiency (CVID) represents a heterogeneous group of primary immunodeficiencies with a wide clinical spectrum. Whole-exome and whole-transcriptome sequencing of a CVID patient who developed amyloidosis identified novel, deleterious mutations in the NLRP12 gene. Results suggest that the NLRP12 mutations might contribute to the auto-inflammatory complications experienced by some CVID patients.

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Borte S, Celiksoy MH, Menzel V, et al. Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency - Clinical Immunology

Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway

Using the HiSeq 2500 System, researchers performed exome and targeted sequencing of tumor/normal pairs to identify somatic mutations in gallbladder carcinoma. Sequencing revealed that ErbB signaling was the most extensively mutated pathway and correlated with poor outcomes. These insights into the mutational landscape of gallbladder carcinoma highlight the important role of the ErbB pathway in pathogenesis.

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Li M, Zhang Z, Li X, et al. Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway - Nature Genetics