Complex de novo structural variants are an underestimated cause of rare disorders - Nature Communications

Complex de novo Structural Variants as Key Factors in Rare Disorders

De novo structural variants (dnSVs) play a significant role in rare disorders but remain insufficiently explored. This study analyzes genomic data from over 12,000 families to uncover the frequency, variety, and clinical relevance of complex dnSVs.

Study Overview

The researchers examined whole-genome sequencing data from 12,568 families, which included 13,698 offspring affected by rare diseases, as part of the UK 100,000 Genomes Project. They identified a total of 1,870 dnSVs, creating the largest dataset of such variants to date.

Prevalence and Classification of Complex dnSVs

Complex dnSVs numbered 158 (8.4% of all variants) and were the third most frequent structural variant type after simple deletions and duplications. The authors classified 65% of these variants into 11 distinct subtypes, highlighting their diversity.

Clinical Impact of dnSVs

Genomic Insights

The study also revealed unique genomic features of de novo deletions depending on whether they were inherited from the maternal or paternal origin.

This research emphasizes the critical role of complex dnSVs in rare disorders and stresses the need for specialized genomic analyses to detect these variants accurately.

Author's summary: Complex de novo structural variants significantly contribute to rare diseases but often remain undetected without targeted genomic approaches, underscoring their clinical importance.

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Nature Nature — 2025-11-04

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