Long-read genetic sequencing to clarify unclear genetic diagnoses
Utilizing long-read sequencing to resolve inconclusive diagnoses and uncertainty in genetic testing
This project uses a newer kind of DNA sequencing to try to find clear genetic answers for children and families who got inconclusive or partial genetic test results.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Children's Hosp of Philadelphia NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11306686 on NIH RePORTER |
What this research studies
We will apply third-generation long-read sequencing to a group of children with suspected inherited (Mendelian) disorders who previously had inconclusive exome or genome results. This includes cases with a single variant in a recessive gene, two variants with unknown parental origin or phase, and variants of uncertain significance or imprinting concerns. We will compare the long-read results to the prior short-read testing to see if uncertain findings can be resolved. The work will be done through the clinical lab and bioinformatics team at Children’s Hospital of Philadelphia, with sequencing, analysis, and interpretation to inform diagnoses.
Who could benefit from this research
Good fit: Children (pediatric patients) with suspected inherited disorders who previously received inconclusive or partial results from exome or genome sequencing are the best fit for this work.
Not a fit: People whose condition is not suspected to be genetic or who already have a clear, confirmed genetic diagnosis are unlikely to benefit from this sequencing approach.
Why it matters
Potential benefit: If successful, this could provide definitive genetic diagnoses for more children, reducing uncertainty and helping guide treatment, monitoring, and family planning.
How similar studies have performed: Previous research has shown long-read sequencing can uncover variants missed by short-read methods and has solved some previously inconclusive cases, but it remains an emerging approach that is not yet routine in all clinics.
Where this research is happening
Philadelphia, United States
- Children's Hosp of Philadelphia — Philadelphia, United States (Active)
Researchers
- Principal investigator: Rajagopalan, Ramakrishnan — Children's Hosp of Philadelphia
- Study coordinator: Rajagopalan, Ramakrishnan
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.