Identification of Disease Susceptibility Alleles in the Next Generation Sequencing Era.

The development of next generation sequencing (NGS) technologies has transformed the study of human genetic variation. In less than a decade, NGS has facilitated the discovery of causal mutations in both rare, monogenic diseases and common, heterogeneous disorders, leading to unprecedented improvements in disease diagnosis and treatment strategies. Given the rapid evolution of NGS platforms, it is now possible to analyze whole genomes and exomes quickly and affordably.

Identifying Robertsonian Translocation Carriers by Microarray-Based DNA Analysis.

Objective: To develop a noninvasive prenatal testing improvement that allows identification of Robertsonian translocation carriers.

Methods: Blood samples from 191 subjects, including 7 pregnant and 9 non-pregnant Robertsonian translocation carriers, were analyzed for fetal trisomy and Robertsonian translocation status. Digital Analysis of Selected Regions (DANSR™) assays targeting sequences common to the p arms of 5 acrocentric chromosomes were developed and added to existing DANSR assays.

FN14 expression correlates with MET in NSCLC and promotes MET-driven cell invasion.

The five-year survival rate in advanced non-small cell lung cancer (NSCLC) remains below ten percent. The invasive and metastatic nature of NSCLC tumor cells contributes to the high mortality rate, and as such the mechanisms that govern NSCLC metastasis is an active area of investigation. Two surface receptors that influence NSCLC invasion and metastasis are the hepatocyte growth factor receptor (HGFR/MET) and fibroblast growth factor-inducible 14 (FN14).

Elevated expression of Fn14 in non-small cell lung cancer correlates with activated EGFR and promotes tumor cell migration and invasion.

Lung cancer is the leading cause of cancer deaths worldwide; approximately 85% of these cancers are non-small cell lung cancer (NSCLC). Patients with NSCLC frequently have tumors harboring somatic mutations in the epidermal growth factor receptor (EGFR) gene that cause constitutive receptor activation. These patients have the best clinical response to EGFR tyrosine kinase inhibitors (TKIs).

Identification of causal sequence variants of disease in the next generation sequencing era.

Over the last decade, genetic studies have identified numerous associations between single nucleotide polymorphism (SNP) alleles in the human genome and important human diseases. Unfortunately, extending these initial associative findings to identification of the true causal variants that underlie disease susceptibility is usually not a straightforward task. Causal variant identification typically involves searching through sizable regions of genomic DNA in the vicinity of disease-associated SNPs for sequence variants in functional elements including protein coding, regulatory, and structural sequences.