Sequencing for developmental disorders on a national level – the DDD(UK) study

DDD. It’s probably the most impressive of all exome sequencing studies of 2014 and I almost missed it. Late December last year, the Deciphering Developmental Disorders study was published in Nature, reporting the genetic findings in more than 1,000 patient-parent trios, which were collected in a systematic nation-wide approach in the United Kingdom and Ireland. The analysis of more than 1,600 de novo mutations in this cohort provides another fascinating view into the genetics of neurodevelopmental disorders, independently confirming the role of DNM1 and pointing out several genes that act through either activating or dominant-negative mutations. Let me guide you through a study that comes to the sobering conclusion that even entire nations are too small to understand the genetics of neurodevelopmental disease. Continue reading

SETBP1, ZMYND11, and the power of joint exome and CNV analysis

Parallel worlds. There are two fields of genetics for neurodevelopmental disorders that currently produce large amounts of data – the field of copy number variation analysis and the field of exome sequencing. When assigning pathogenicity, information from both genetic technologies are rarely considered jointly. A recent study in Nature Genetics now performs a combined analysis of a large CNV and exome datasets in intellectual disability and autism. Interestingly, this method produces robust results, highlighting novel causative genes. Continue reading