Rare Disease

Structural variants are essential for diagnosing many genetic disorders and understanding their inheritance patterns.

Structural variants (SVs) often underlie the pathogenic mechanisms of various rare diseases and understanding them is essential for precise diagnosis, prognosis, and the development of targeted therapeutic strategies. Current technologies fail to identify most balanced and unbalanced structural variants. For example, balanced events like Robertsonian translocations and other complex translocations:

• Cannot be detected using microarrays due to a lack of DNA dosage change¹
• Are typically too large to be identified via short read ensemble technologies – breakpoints often contain high GC or repetitive sequences that make localization impossible
• Are typically too small to be detected using traditional cytogenetics methods like karyotyping
• Are too complex to be deciphered by short-read sequencing

Efficient genome mapping provides information that traditional cytogenetics and short-read sequencing cannot and thus significantly improves the identification of SVs implicated in rare diseases. Resulting use of this technology will improve the diagnostic yield for patients with rare diseases. Genomic SVs contribute to the complexity of inheritance patterns observed in rare genetic diseases. They often manifest as de novo mutations, but also can be inherited from one or both parents, or arise as complex rearrangements that challenge traditional Mendelian inheritance patterns.

The understanding of altered gene expression as a result of structural variation provides the underpinnings necessary to unravel genetically driven disease mechanisms. Access to information provided through genome mapping enables researchers to identify potential therapeutic targets for drug discovery. This knowledge is instrumental in the development of novel therapeutic approaches for rare genetic diseases².

Understanding the functional impact of SVs is crucial for targeted therapeutic interventions. Recent publications underscore the influence of SVs on gene function, expression, and cellular pathways, providing valuable insights into disease mechanisms³.

Electronic genome mapping enables a comprehensive understanding of SVs at the whole genome level, aiding in precise diagnosis, elucidation of inheritance patterns, and unraveling disease mechanisms and accelerating therapeutic discovery. By incorporating these tools into genomics research and clinical practice, lab directors can significantly enhance the research and diagnostic accuracy thereby improving patient outcomes for individuals affected by rare genetic diseases.