Duke researchers have connected very rare and precise duplications and deletions in the human genome to their complex disease consequences by duplicating them in zebrafish.
The findings are based on detailed studies of five people missing a small fragment of their genome and suffering from a mysterious syndrome of craniofacial features, visual anomalies and developmental delays.
When those patient observations were coupled to analyses of the anatomical defects in genetically altered zebrafish embryos, the researchers were able to identify the contribution specific genes made to the pathology, demonstrating a powerful tool that can now be applied to unraveling many other complex and rare human genetic conditions.
The findings are broadly important for human genetic disorders because copy-number variants (CNVs) — fragments of the genome that are either missing or existing in extra copies — are quite common in the genome. But their precise contribution to diseases has been difficult to determine because CNVs can affect the function of many genes simultaneously.