Syzygy

Syzygy identifies genetic variants from pooled sequencing data to discover and validate candidate mutations underlying mitochondrial complex I respiratory chain disorders.

Key Features:

• Focused Candidate Gene Prediction: Predicts candidate genes implicated in mitochondrial disorders and targets a curated set of 103 candidate genes for analysis.
• High-Throughput Sequencing: Performs deep sequencing of selected candidate genes across pooled DNA samples (seven pools from 103 cases and 42 healthy controls).
• Variant Identification: Detects rare variants predicted to affect protein function, identifying 151 such variants in the reported study.
• Experimental Validation: Enables experimental validation including cDNA complementation assays that confirmed pathogenic mutations in NUBPL and FOXRED1.
• Genetic Diagnosis Establishment: Contributed to establishing genetic diagnoses in 13 individuals among 60 previously unsolved cases.

Scientific Applications:

• Mitochondrial disease mutation discovery: Facilitates discovery and validation of causal mutations in complex I respiratory chain disorders across mitochondrial and nuclear genes.

Methodology:

Creates pooled DNA cohorts from cases and controls, performs deep sequencing of candidate genes, and predicts rare protein-affecting variants from the pooled sequence data.