Fig. 1

Overview of experimental design. We performed whole-genome sequencing, RNA sequencing, and clinical phenotyping on five large families (32 total individuals) with the 16p12.1 deletion, indicated with red asterisks in the pedigrees. Children (green) and adults (blue) in the pedigrees are shaded by phenotypic severity score, with white indicating no clinical features, lighter shades indicating mild features (child de Vries score of 1-4; adult score of 1–2 features), medium shades indicating moderate features (child de Vries score of 5–8; adult score of 3–4 features), darker shades indicating severe features (child de Vries score of 9–13; adult score of 5–6 features), and grey indicating no phenotypic data available. Phenotypic severity scores are described in the Methods and are listed for each person in Additional file 2: Tables S2-S3. We then performed multiple analyses to assess the role of the deletion and rare “second-hit” variants towards the observed transcriptomic changes and developmental phenotypes, including differential expression between carriers and noncarriers of the deletion, differential expression between parents and carrier offspring in 13 trios from the five families, outlier gene expression among all individuals, identification of additional transcriptomic alterations such as alternative splicing and allele-specific expression, and gene interaction patterns in the context of a brain-specific network