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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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Miranda

Miranda Galey, MS

Lab Manager

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Pax

Pax Reed

Research Scientist

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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.




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SEQUENCING SERVICES

We provide long-read sequencing on the Oxford Nanopore Technologies (ONT) platform to researchers at UW, SCH, SCRI, FHRC, external institutions, and private companies. Services include whole-genome sequencing, targeted sequencing, RNA sequencing, variant calling and phasing, and methylation calling. If you are interested in long-read sequencing services, please contact us to discuss options and costs.



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PUBLICATIONS

2022
2021







JOIN US!

In the Miller Lab, we believe training the next generation of scientists – at all levels – is one of our most important responsibilities. You'll be joining a friendly group of people with diverse backgrounds. Our lab is heavily computational, but benchwork is also necessary. If you're looking for a fun, collaborative, and productive work environment, we'd love to hear from you! Please email with any inquiries. email


Postdoctoral Researcher

We're currently recruiting for a postdoc position. Ideal candidates should have programming knowledge as well as wet lab experience and an interest in long-read sequencing. Click below for more information.

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Graduate students

Mentoring students is one of our most important responsibilities. 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.


Undergraduates

We also welcome undergraduate students in our lab. Please reach out if you're interested!







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