Description:

Alexandre Reymond
Center for Integrative Genomics, University of Lausanne, Genopode building, CH-1015 Lausanne, Switzerland

Recurrent 600kb-long genomic rearrangements at 16p11.2 BP4-5 represent one of the most common causes of genomic disorders. They are mediated by human-specific duplications that appeared at the beginning of the modern human lineage, suggesting that their expansion has a possible evolutionary advantage that outweighs chromosomal instability.

These copy number variants (CNVs) are among the most frequent genetic causes of neurodevelopmental and psychiatric disorders, as they are found in 1% of individuals with autism spectrum disorders and schizophrenia. They were also originally associated with reciprocal defects in head size and body weight, but have since been associated with a plethora of phenotypic alterations, albeit with high variability in expressivity and incomplete penetrance. Revealing the complex and variable clinical manifestations of these CNVs is crucial for accurate diagnosis and personalized treatment strategies for carriers.

The 16p11.2 BP4-5 CNVs showcase variable expressivity and pleiotropy, as they are deleterious enough to be enriched in clinical cohorts but not enough so to be absent from population cohorts.