Melissa Gymrek
University of California-San Diego, CA·Genetics
Genome-wide association studies (GWAS) have linked thousands of DNA regions to human traits and diseases, but they mostly test simple single-letter changes. Harder-to-read parts of the genome, such as repeated sequences and structurally complex regions, are usually skipped, even though they may carry many disease-causing variants.
- Fields
Genetics
Computer Science
- Topics
human genetics
statistical genetics
genomics
- Grants
- 3 known grants, through Jun 2028
What they work on
- Develop scalable methods for tandem repeat (TR)-based GWAS that genotype repeats directly from UK Biobank and All of Us whole genome sequences, producing a catalog of TRs linked to complex traits.
- Measure how tens of thousands of TRs affect gene regulation using massively parallel reporter assays (MPRA), which test many DNA sequences at once and were optimized here for repetitive sequences.
- Characterize candidate medically relevant TRs in induced pluripotent stem cells and their differentiated derivatives from ancestrally diverse donors, using the lab's genome editing frameworks.
- Develop methods to profile repeat variants, including STRs, VNTRs and segmental duplications, from long-read sequencing data so repeats can be included in Mendelian disease analysis.
- Extend short-read repeat genotyping to long, imperfect and GC-rich repeats and to somatic changes in repeat length, and build a framework to prioritize likely pathogenic repeat mutations.
- Build a web-based pangenome browser that lets non-experts explore graph-based genome regions alongside linear-reference data, and develop local graph complexity metrics to characterize existing GWAS signals.
- Integrate Human Pangenome Reference Consortium pangenomes with UK Biobank and All of Us genotype and phenotype data to fine-map trait-associated loci by finding graph paths enriched in people with a trait.
More about the research
These projects build computational tools and experiments to bring those overlooked regions into human genetics. They draw on whole genome sequencing (WGS) and large biobanks such as UK Biobank and All of Us.
Why it matters
Repeats and structurally complex regions underlie conditions such as Huntington's disease, Fragile X syndrome, hereditary ataxias, Lynch syndrome, hearing loss and medullary cystic kidney disease. Adding these variants to standard WGS pipelines could let a single genetic test detect disease variants that current pipelines miss. Catalogs of trait-linked repeats and openly available pangenome software could help researchers pinpoint causal variants for common traits across diverse ancestries.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Systematic characterization of tandem repeat variants contributing to complex traits
NIH · Sep 2020 – Jun 2028
Integrating the reference pangenome with biobank-scale data for complex trait analysis
NIH · Sep 2024 – Aug 2027
Refining Mendelian disease analysis via detection of clinically relevant repeat variants
NIH · Sep 2018 – Feb 2027
Closest labs
Harriet Dashnow
University of Colorado Denver/Anschutz Medical Campus, CO·Genetics·Early-career
Build a public, population-scale catalog of short tandem repeat variation grouped by ancestry, emphasizing diverse and underserved populations, so disease-causing repeat expansions can be prioritized.
Hyejung Won
University of North Carolina at Chapel Hill, NC·Genetics
Develop single-cell massively parallel reporter assays (scMPRA), which combine DNA barcoding with single-cell RNA sequencing, to measure thousands of Alzheimer's-linked regulatory elements in different brain cell types at once.
Anat Kreimer
Rutgers University-New Brunswick, NJ·Genetics
Develop methods that integrate massively parallel reporter assay (MPRA) data, which test thousands of DNA sequences at once, with other genomic assays and deep learning to reconstruct cell-type-specific gene regulatory networks and their condition-specific regulators.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
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