A cross-disorder dosage sensitivity map of the human genome

Large copy number variants (CNVs) are strong risk factors for human developmental disorders, yet interpretation of their functional consequences remains a considerable challenge, particularly for partial or complete duplication of a gene. Here, CGM Investigators Mike Talkowski and Harrison Brand jointly analyzed genetic data from nearly one-million individuals across 54 disorders to produce a ‘dosage sensitivity’ map of human diseases. This catalog nominated 163 disease-relevant loci and used a machine learning approach to create dosage sensitive metrics (pHaplo and pTriplo) that predicted 2,987 genes intolerant to deletion and 1,559 triplosensitive genes that were intolerant to duplication. These metrics were openly distributed and have been integrated into the DECIPHER database.

Read more in Science Direct

December 21, 2022


CGM Primary Investigator

Mike Talkowski

Harrison Brand