Transcriptome-wide outlier approach identifies individuals with minor spliceopathies.

ABSTRACT: RNA-sequencing has improved the diagnostic yield of individuals with rare diseases. Current analyses predominantly focus on identifying outliers in single genes that can be attributed to cis-acting variants within the gene locus. This approach overlooks causal variants with trans-acting effects on splicing transcriptome-wide, such as variants impacting spliceosome function. We present a transcriptomics-first method to diagnose individuals with rare diseases by examining transcriptome-wide patterns of splicing outliers. Using splicing outlier detection methods (FRASER and FRASER2) we characterized splicing outliers from whole blood for 390 individuals from the Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) and Undiagnosed Diseases Network (UDN) consortia. We examined

SUBMITTER: Arriaga MT 

PROVIDER: S-EPMC11722475 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature