Kelly A. Frazer

A genome-wide approach to identifying novel-imprinted genes

Published in Annual Review of Genomics and Human Genetics

Reversion to an embryonic alternative splicing program enhances leukemia stem cell self-renewal.

Published in Proceedings of the National Academy of Sciences

Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. In this study, RNA sequencing, splice isoform-specific quantitative RT-PCR, lentiviral transduction, and in vivo humanized mouse mo...

Network-based analysis identifies epigenetic biomarkers of esophageal squamous cell carcinoma progression.

Published in Bioinformatics

Homozygous GNAS 393C-allele carriers with locally advanced esophageal cancer fail to benefit from platinum-based preoper...

Published in Annals of Surgical Oncology

Genome-wide mutational landscape of mucinous carcinomatosis peritonei of appendiceal origin.

Published in Genome Medicine

High-resolution mutational profiling suggests the genetic validity of glioblastoma patient-derived pre-clinical models.

Recent advances in the ability to efficiently characterize tumor genomes is enabling targeted drug development, which requires rigorous biomarker-based patient selection to increase effectiveness. Consequently, representative DNA biomarkers become equally important in pre-clinical studies. However, it is still unclear how well these markers are mai...

A Pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition.

Published in Cell Stem Cell

Leukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression to blast crisis (BC), in part, through the alternative splicing of self-renewal and survival genes. To elucidate splice-isoform regulators of human BC LSC maintenance, we performed whole-transcr...

ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia.

Published in Proceedings of the National Academy of Sciences

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...

BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma.

Published in Journal of Translational Medicine

Elucidating the role of 8q24 in colorectal cancer.

Published in Nature Genetics

Genomewide SNP variation reveals relationships among landraces and modern varieties of rice.

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...

Common sequence polymorphisms shaping genetic diversity in Arabidopsis thaliana.

Published in Science

The genomes of individuals from the same species vary in sequence as a result of different evolutionary processes. To examine the patterns of, and the forces shaping, sequence variation in Arabidopsis thaliana, we performed high-density array resequencing of 20 diverse strains (accessions). More than 1 million nonredundant single-nucleotide polymor...

The genomics gold rush.

Published in JAMA

Evaluation of the SNP tagging approach in an independent population sample—array-based SNP discovery in Sami.

Published in Human Genetics

Significant efforts have been made to determine the correlation structure of common SNPs in the human genome. One method has been to identify the sets of tagSNPs that capture most of the genetic variation. Here, we evaluate the transferability of tagSNPs between populations using a population sample of Sami, the indigenous people of Scandinavia. Ar...

Noncoding sequences conserved in a limited number of mammals in the SIM2 interval are frequently functional.

Published in Genome Research

Cross-species DNA sequence comparison is a fundamental method for identifying biologically important elements, because functional sequences are evolutionarily conserved, wheres nonfunctional sequences drift. A recent genome-wide comparison of human and mouse DNA discovered over 200,000 conserved noncoding sequences with unknown function. Multispeci...

Transcriptome sequencing reveals potential mechanism of cryptic 3 splice site selection in SF3B1-mutated cancers.

Published in PLoS Computational Biology

Mutations in the splicing factor SF3B1 are found in several cancer types and have been associated with various splicing defects. Using transcriptome sequencing data from chronic lymphocytic leukemia, breast cancer and uveal melanoma tumor samples, we show that hundreds of cryptic 3 splice sites (3 SSs) are used in cancers with SF3B1 mutations. We ...

Multi-species sequence comparison: the next frontier in genome annotation.

Published in Genome Biology

Multi-species comparisons of DNA sequences are more powerful for discovering functional sequences than pairwise DNA sequence comparisons. Most current computational tools have been designed for pairwise comparisons, and efficient extension of these tools to multiple species will require knowledge of the ideal evolutionary distance to choose and the...

Functional screening of an asthma QTL in YAC transgenic mice.

Published in Nature Genetics

Many quantitative trait loci (QTLs) contributing to genetically complex conditions have been discovered, but few causative genes have been identified. This is mainly due to the large size of QTLs and the subtle connection between genotype and quantitative phenotype associated with these conditions. Transgenic mice have been successfully used to ana...

Computational and biological analysis of 680 kb of DNA sequence from the human 5q31 cytokine gene cluster region.

Published in Genome Research

With the human genome project advancing into what will be a 7- to 10-year DNA sequencing phase, we are presented with the challenge of developing strategies to convert genomic sequence data, as they become available, into biologically meaningful information. We have analyzed 680 kb of noncontiguous DNA sequence from a 1-Mb region of human chromosom...

The apolipoprotein(a) gene is regulated by sex hormones and acute-phase inducers in YAC transgenic mice.

Published in Nature Genetics

High plasma concentrations of apolipoprotein (a) (apo(a)) have been implicated as a major independent risk factor for atherosclerosis in humans. Apo(a) is a large, evolutionarily new gene (present primarily in primates) for which considerable controversy exists concerning the factors that regulate its expression. To investigate the in vivo regulati...