Ed Blair

Journal Article Question Threat and Response Bias Get access NORMAN M. BRADBURN, NORMAN M. BRADBURN chairman Department of Behavioral Sciences, and Senior Study Director, National Opinion Research Center, University of Chicago; Search for other works by this author on: Oxford Academic Google Scholar SEYMOUR SUDMAN, SEYMOUR SUDMAN Business Administration Sociology and the Survey Research Laboratory, University of Illinois at Urbana-Champaign Search for other works by this author on: Oxford Academic Google Scholar ED BLAIR, ED BLAIR Assistant Professor of Marketing University of Houston Search for other works by this author on: Oxford Academic Google Scholar CAROL STOCKING CAROL STOCKING Senior Survey Director National Opinion Research Center, University of Chicago Search for other works by this author on: Oxford Academic Google Scholar Public Opinion Quarterly, Volume 42, Issue 2, SUMMER 1978, Pages 221–234, https://doi.org/10.1086/268444 Published: 01 January 1978

This article reports a nationwide study of response effects based on answers from almost 1,200 respondents to threatening behavioral questions presented in various formats. Results indicate that threatening questions requiring yes-or-no answers can be asked in any format, but that threatening questions requiring quantified answers are best asked in open-ended, long questions with respondent-familiar wording.

Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes 1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome 2 . We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5′ splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.