Published in Genome Biology
BackgroundThe National Children’s Study (NCS) is a prospective epidemiological study in the USA tasked with identifying a nationally representative sample of 100,000 children, and following them from their gestation until they are 21 years of age. The objective of the study is to measure environmental and genetic influences on growth, development, ...
Published in Breast Cancer Research
IntroductionThe increasing number of targeted therapies, together with a deeper understanding of cancer genetics and drug response, have prompted major healthcare centers to implement personalized treatment approaches relying on high-throughput tumor DNA sequencing. However, the optimal way to implement this transformative methodology is not yet cl...
Published in The American Journal of Human Genetics
The hypoxic conditions at high altitudes present a challenge for survival, causing pressure for adaptation. Interestingly, many high-altitude denizens (particularly in the Andes) are maladapted, with a condition known as chronic mountain sickness (CMS) or Monge disease. To decode the genetic basis of this disease, we sequenced and compared the whol...
Published in Proceedings of the National Academy of Sciences of the United States of America
The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated by adenosine deaminase act...
Published in Genome Biology
Ultra-deep targeted sequencing (UDT-Seq) can identify subclonal somatic mutations in tumor samples. Early assays' limited breadth and depth restrict their clinical utility. Here, we target 71 kb of mutational hotspots in 42 cancer genes. We present novel methods enhancing both laboratory workflow and mutation detection. We evaluate UDT-Seq true sen...
Published in Bioinformatics (Oxford, England)
Paired-end whole transcriptome sequencing provides evidence for fusion transcripts. However, due to the repetitiveness of the transcriptome, many reads have multiple high-quality mappings. Previous methods to find gene fusions either ignored these reads or required additional longer single reads. This can obscure up to 30% of fusions and unnecessar...
Published in Proceedings of the National Academy of Sciences of the United States of America
Through long-term laboratory selection (over 200 generations), we have generated Drosophila melanogaster populations that tolerate severe, normally lethal, levels of hypoxia. Because of initial experiments suspecting genetic mechanisms underlying this adaptation, we compared the genomes of the hypoxia-selected flies with those of controls using dee...
Published in PLoS computational biology
Genome wide association (GWA) studies, which test for association between common genetic markers and a disease phenotype, have shown varying degrees of success. While many factors could potentially confound GWA studies, we focus on the possibility that multiple, rare variants (RVs) may act in concert to influence disease etiology. Here, we describe...
Published in Proceedings of the National Academy of Sciences
Rice, the primary source of dietary calories for half of humanity, is the first crop plant for which a high-quality reference genome sequence from a single variety was produced. We used resequencing microarrays to interrogate 100 Mb of the unique fraction of the reference genome for 20 diverse varieties and landraces that capture the impressive gen...
Published in Genome Biology
New technologies for rapidly assaying DNA sequences have revealed that the degree and nature of human genetic variation is far more complex then previously realized. These same technologies have also resulted in the identification of common genetic variants associated with more than 30 human diseases and traits.
