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University of Washington   |   Department of Pediatrics   |   Department of Laboratory Medicine & Pathology

Around 50% of individuals with a suspected genetic disorder remain undiagnosed after a complete clinical evaluation, which often takes years to complete. We believe this burden on patients and families is simply too high. In the Miller Lab, our goals are twofold: to improve the efficiency and effectiveness of genetic testing, and to better understand human genetic disease through the identification and characterization of novel disease-causing variation.


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OUR TEAM

Danny

Danny Miller, MD, PhD

Principal Investigator

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Nikhita

Nikhita Damaraju, MS

PhD Student

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Miranda

Miranda Galey, MS

Lab Manager

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Joy

Joy Goffena, MS

Research Scientist

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Angie

Angie Miller

Research Coordinator

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NEWS & VIEWS





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RESEARCH

Unsolved genetic disorders

We are interested in understanding why 50% of individuals with a suspected genetic disorder remain unsolved after a complete clinical evaluation. Using long-read DNA and RNA seqeuencing, we have identified disease-causing variants that are difficult or impossible to resolve using standard clinical testing. We are always happy to collaborate, so reach out if you have a challenging unsolved case.

Clinical applications of long-read sequencing

Standard clinical genetic testing can take years to complete and is diagnostic only 50% of the time. It's a challenging process often referred to as the diagnostic odyssey. We are working to change this paradigm by using long-read sequencing as a single test in the clinical setting. Our efforts extend beyond the genetics clinic into spaces such as cancer biology and infectious disease.

Structural variation

A big challenge when analyzing long-read sequencing data is interperting all of the structural variants that are found. In collaboration with Oxford Nanopore, we are seqeuencing a large number of 1000G Project samples to understand what normal human structural variation looks like and to build a database of controls for everyone to use. Check out the 1000G ONT Consortium site for more information.
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Methylation

Because long-read seqeuncing data contain signal for both the DNA sequence and methylation status, we can identify differences in methylation in unsolved cases and healthy controls. We are building tools to identify differences in methylation genome-wide and understand what methylation looks like in a large number of healthy controls.

Genome assembly and analysis

This is how we got into Nanopore sequencing! We are always interested in sequencing and assembling genomes from all critters big and small. We're part of a large group working on sequencing all of the species in the Drosophila species group, and we're interested in all types of genome assembly projects.

Long-read RNA sequencing

Sequencing of native RNA is just cool. We do RNA seqeuncing of our unsolved clinical cases and are interested in using long reads to identify tissue-specific isoforms and expression. Also, what are all those RNA modifications doing? Sequencing of native RNA from different tissues is going to be interesting.




Sequencing Services

SEQUENCING SERVICES

The Miller Lab operates the University of Washington Nanopore Sequencing Core, which provides long-read sequencing on the Oxford Nanopore Technologies (ONT) platform to researchers at UW, SCH, SCRI, FHCC, external institutions, and private companies. Services include whole-genome sequencing, RNA sequencing, variant calling and phasing, and methylation calling. If you are interested in long-read sequencing services, please visit the UW Nanopore Sequencing Core site or email us for more information about options and costs.



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PUBLICATIONS

2023
  • Miller DE, Dorador AP, Van Vaerenberghe K, Li A, Grantham EK, Cerbin S, Cummings C, Barragan M, Egidy RR, Scott AR, Hall KE, Perera A, Gilliland WD, Hawley RS, Blumenstiel JP. Off-target piRNA gene silencing in Drosophila melanogaster rescued by a transposable element insertion. PLoS Genet. 2023 Feb 21;19(2):e1010598. PMID: 36809339
  • Stergachis AB, Blue EE, Gillentine MA, Wang LK, Schwarze U, Cortés AS, Ranchalis J, Allworth A, Bland AE, Chanprasert S, Chen J, Doherty D, Folta AB, Glass I, Horike-Pyne M, Huang AY, Khan AT, Leppig KA, Miller DE, Mirzaa G, Parhin A, Raskind W, Rosenthal EA, Sheppeard S, Strohbehn S, Sybert VP, Tran TT, Wener M, University of Washington Center for Mendelian Genomics (UW-CMG), Undiagnosed Diseases Network (UDN), Byers PH, Nelson SF, Bamshad MJ, Dipple KM, Jarvik GP, Hoppins S, Hisama FM. Full-length isoform sequencing for resolving the molecular basis of Charcot-Marie-Tooth 2A. bioRxiv [Preprint]. 2023 Feb 7:2023.02.07.526487. PMID: 36798371
  • Wojcik MH, Reuter CM, Marwaha S, Mahmoud M, Duyzend MH, Barseghyan H, Yuan B, Boone PM, Groopman EE, Délot EC, Jain D, Sanchis-Juan A, Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium, Starita LM, Talkowski M, Montgomery SB, Bamshad MJ, Chong JX, Wheeler MT, Berger SI, O'Donnell-Luria A, Sedlazeck FJ, Miller DE. Beyond the exome: what's next in diagnostic testing for Mendelian conditions. ArXiv [Preprint]. 2023 Jan 18:arXiv:2301.07363v1. PMID: 36713248
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JOIN US!

Research in the Miller Lab is a healthy mix of computational and bench science. We believe that training the next generation of scientists – at all levels – is one of our most important responsibilities. While we value hard work, we also know work–life balance matters, so if you'd like to be part of a respectful, collaborative, and productive team, we'd love to hear from you! Feel free to email with any inquiries. email

Postdoctoral Researcher

We're currently recruiting for a postdoc position. To apply, please provide a current CV, a summary of your research accomplishments/goals/interests, and contact info for at least three references. Ideal candidates will have programming knowledge as well as wet lab experience and an interest in long-read sequencing. Click here for more information.

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Research Scientist/Technician

This position primarily involves preparing samples for DNA and RNA sequencing on the Oxford Nanopore platform. This is a great opportunity for an organized individual with basic laboratory skills.

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Graduate students

Grad students who want to learn more about long-read DNA or RNA sequencing, structural variation, genome assembly, or developing long-read-sequencing-based clinical tests are encouraged to rotate in our lab. We are currently able to accept MCB and M3D grad students, and we're hoping to include other UW programs soon. Stay tuned!

Undergraduates

We are now accepting applications for summer undergrads. To apply for an undergraduate position, please submit your current CV, including any relevant experience or courses you've taken, as well as a couple paragraphs about why you want to do research and why in our lab specifically.







SUPPORT

We are grateful for the generous support our research program receives from the National Institutes of Health Early Independence Award as well as private foundation support from the Brotman Baty Institute for Precision Medicine.

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CURRENT FUNDING
  • National Institutes of Health Director’s Early Independence Award (DP5): Long-read DNA and RNA sequencing to identify disease-causing genetic variation and streamline testing. (September 2022–August 2027) Miller DE (PI).
  • Brotman Baty Institute: Establishment of a long-read sequencing cost center. (2021–2024) Miller DE (PI).
  • Brotman Baty Institute (2022 Catalytic Collaborations): Investigation of new molecular diagnostics for mitochondrial disorders. (2022–2023) Miller DE (Co-PI).
PREVIOUS FUNDING
  • Brotman Baty Institute (2021 Catalytic Collaborations): Targeted long-read sequencing to resolve complex structural variants and identify missing variants. (2021–2022) Miller DE (PI).
  • Brotman Baty Institute (2019 Catalytic Collaborations): Long-read whole-genome sequencing of unsolved Mendelian cases of disease. (2020–2021) Miller DE (Co-PI).
MAKE A DONATION

We appreciate your interest in our research. If you would like to make a contribution to a Miller Lab study, please write a brief letter designating the funds to research by Danny E. Miller, MD, PhD, and indicate the study topic you wish to support. Include your name and address in the letter, and send it with a check or money order to:

Miller Laboratory, Department of Pediatrics
University of Washington
1959 NE Pacific Street, Box 356320
Seattle, WA 98195-6320