Frazer Lab Department of Pediatrics, Genome Information Sciences

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Welcome to the Frazer Lab!

We are using two complementary approaches to achieve our goal of identifying and characterizing functional human genetic variants. Our first approach utilizes iPSCORE, a resource that was generated to enable both familial and association-based genetic studies of molecular and physiological phenotypes in induced pluripotent stem cells (iPSCs) and derived cell types. Our second approach involves conducting association studies in well-characterized cohorts with the goal of identifying variants that play roles in human disease and to assess their contributions to disease pathogenesis, progression, and prognosis.

iPSCORE (iPSC Collection for Omics Research)

    Induced pluripotent stem cells (iPSCs), derived from human adult cells and capable of being differentiated to become a variety of cell types, are a powerful tool for studying how genetic variants associate with human molecular phenotypes. Over the past six years, our lab has systematically derived and characterized a unique collection of iPSC lines from 222 individuals - iPSCORE. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic CNVs) as determined using high-throughput RNA-seq and genotyping arrays, respectively. The participants were recruited to include 41 families, twins, and individuals of diverse ethnicity to enable genetic studies investigating the segregation of traits. Due to the fact that some of the individuals in the 41 families are only related by marriage, there are a total of 136 genetically unrelated individuals in the collection. All individuals in iPSCORE have whole genome sequence data. We are currently using these lines to conduct genotype-molecular phenotype correlations in both pluripotent stem cells and a variety of iPSC-derived cell types including cardiomyocytes (iPSC-CMs), pancreatic precursor cells (iPSC-PPCs), and retina pigment epithelium cells (iPSC-RPEs). iPSCORE provides a powerful tool to examine how genetic variants influence molecular and physiological traits across a variety of derived cell types, as well as to functionally interrogate variants underlying a variety of GWAS phenotypes.

Human genetic studies

    We collaborate with Drs. Bing Ren, Maike Sander and Kyle Gaulton in two large NIDDK funded multi-PI studies. One project is funded to identify and functionally annotate T2D causal genetic variants as well as variants with potential regulatory importance in human islet cells. We have identified a comprehensive set of variants through the systematic analysis of large genetic and epigenetic datasets and are currently analyzing the results of downstream high throughput functional assays. The second project is funded to increase our understanding of T1D GWAS variants. Here, we are taking advantage of iPSCORE to characterize T1D causal variants that are functional during development in pancreatic precursor cells.

    We also collaborate with Dr. Radha Ayyagari at the Shiley Eye Institute at UC San Diego to identify new genes involved in inherited retinal dystrophies (IRD). We have generated whole genome sequence (WGS) data for 454 individuals from 126 pedigrees segregating IRD; 227 subjects are affected by IRD and 227 are unaffected. Our analyses have identified new genes that can underlie IRD as well as new types of mutations that can be present in known IRD genes. The study is funded by the NEI and the Foundation Fighting Blindness.

Kelly A Frazer, Ph D

    Dr. Frazer is an internationally renowned leader in the field of genome biology and medicine. She is the director of UC San Diego Institute for Genomic Medicine and founding chief of the Division of Genome Information Sciences in the Department of Pediatrics at UC San Diego.

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