2%) in a genome-wide siRNA screen for hESC cell proliferation22 (Fig. 2c, Extended Data Fig. 4; Supplementary Table 2). This approach identified BCL2L112 on chr20q11.21, EIF4A3, NOL11 and seven other genes on chr17q and UTP6 and SUZ12 on chr17q11.2. One candidate, EIF4A3, scored more highly than BCL2L1 in reducing ESC proliferation (Fig. 2c, top 0.1% of genes), was highly expressed in iPSCs, and over-expressed in lines with increased copy number, at both the mRNA (Q = 2x10-5) and protein level (Extended Data Fig. 5). Finally, we compared lines from the same donor with and without CNAs to test for genome-wide effects on gene expression levels and, in a subset of cases, for effects on cell growth, proliferation and apoptosis (Fig. 2b, Extended Data Fig. 5). The recurrent duplication on chromosome 17 was associated with the largest number of changes in gene expression, including 1,098 genes (FDR < 1%) in trans located on other chromosomes, which were enriched for ‘Neural Crest Differentiation’ and ‘DNA strand elongation’ pathways (PathCards23, Supplementary Table 2). We also detected significant increases and decreases in cell growth rate associated with CNAs on chromosome 17 and 20 (Extended Data Fig. 5).
