Long-read sequencing reveals how structural variations affect gene expression in the brain
Author Information
Author(s): Billingsley Kimberley J., Meredith Melissa, Daida Kensuke, Alvarez Jerez Pilar, Negi Shloka, Malik Laksh, Genner Rylee M., Moller Abraham, Zheng Xinchang, Gibson Sophia B., Mastoras Mira, Baker Breeana, Kouam Cedric, Paquette Kimberly, Jarreau Paige, Makarious Mary B., Moore Anni, Hong Samantha, Vitale Dan, Shah Syed, Monlong Jean, Pantazis Caroline B., Asri Mobin, Shafin Kishwar, Carnevali Paolo, Marenco Stefano, Auluck Pavan, Mandal Ajeet, Miga Karen H., Rhie Arang, Reed Xylena, Ding Jinhui, Cookson Mark R., Nalls Mike, Singleton Andrew, Miller Danny E., Chaisson Mark, Timp Winston, Gibbs J. Raphael, Phillippy Adam M., Kolmogorov Mikhail, Jain Miten, Sedlazeck Fritz J., Paten Benedict, Blauwendraat Cornelis
Primary Institution: Cold Spring Harbor Laboratory
Hypothesis
Long-read sequencing can uncover the impact of structural variants on gene expression and DNA methylation in the human brain.
Conclusion
The study shows that large-scale long-read sequencing can identify complex regulatory mechanisms in the brain that were previously inaccessible.
Supporting Evidence
- The study identified approximately 234,905 structural variants in the brain samples.
- Locally phased assemblies covered 95% of all protein-coding genes in the human genome.
- Quantitative trait locus analyses were applied to identify structural variants impacting gene expression.
Takeaway
Scientists used a new method to look at many brains and found important changes in genes that could help us understand brain diseases.
Methodology
The study utilized long-read sequencing with a new scalable protocol and computational pipeline on brain samples from two cohorts.
Participant Demographics
Samples were from neurologically normal controls of European and African or African admixed ancestry.
Digital Object Identifier (DOI)
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