ABSTRACT
While short-read sequencing currently dominates genetic research and diagnostics, it frequently falls short of capturing certain structural variants (SVs), which are often implicated in the etiology of neurodevelopmental disorders (NDDs). Optical genome mapping (OGM) is an innovative technique capable of capturing SVs that are undetectable or challenging-to-detect via short-read methods. This study aimed to investigate NDDs using OGM, specifically focusing on cases that remained unsolved after standard exome sequencing. OGM was performed in 47 families using ultra-high molecular weight DNA. Single-molecule maps were assembled de novo, followed by SV and copy number variant calling. We identified 7 variants of interest, of which 5 (10.6%) were classified as likely pathogenic or pathogenic, located in BCL11A, OPHN1, PHF8, SON, and NFIA. We also identified an inversion disrupting NAALADL2, a gene which previously was found to harbor complex rearrangements in two NDD cases. Variants in known NDD genes or candidate variants of interest missed by exome sequencing mainly consisted of larger insertions (> 1kbp), inversions, and deletions/duplications of a low number of exons (1-4 exons). In conclusion, in addition to improving molecular diagnosis in NDDs, this technique may also reveal novel NDD genes which may harbor complex SVs often missed by standard sequencing techniques.
Subject(s)
Chromosome Mapping , DNA Copy Number Variations , Neurodevelopmental Disorders , Humans , Neurodevelopmental Disorders/genetics , Neurodevelopmental Disorders/diagnosis , Female , Male , Chromosome Mapping/methods , Exome Sequencing/methods , Child , Genomic Structural Variation , Child, PreschoolABSTRACT
Subjective feelings of risk are a central feature of everyday life, and evidence shows that people who do not conform to contemporary normative notions are often more exposed to everyday risks than others. Despite this, normative notions are rarely acknowledged as risk objects. By drawing on the theory of 'doing' and 'undoing' risk, which combines intersectional and risk theory, this study contributes new perspectives on the everyday risks in contemporary society that face people who many would label as being 'at risk' - lesbian, gay, bisexual and transgender people. The study consists of five focus group interviews with lesbian, gay, bisexual and transgender people of different ages in Sweden. Findings pinpoint risks and how these are done and un-done in different spheres of interviewees' lives: the emotional risks prevailing in their private lives; the risk of discrimination at work and in relations with other institutions; and the risk of violence and harassment in public places. These risks are all related to the heteronormative order in which the mere fact of being lesbian, gay, bisexual and transgender is perceived as a risk.
Subject(s)
Bisexuality/psychology , Homosexuality, Female/psychology , Homosexuality, Male/psychology , Prejudice , Social Stigma , Transsexualism/psychology , Adult , Female , Focus Groups , Humans , Male , Social Perception , Sweden , Young AdultABSTRACT
In evaluating complex new technologies, people are usually dependent on information provided by others, for example, experts or journalists, and have to determine whether they can trust these information sources. This article focuses on similarity as the basis for trust. The first experiment (N = 261) confirmed that a journalist writing about genetically modified (GM) food was trusted more when his attitude was congruent with that of his readers. In addition, the experiment showed that this effect was mediated by the perceived similarity of the journalist. The second experiment (N = 172) revealed that trust in a journalist writing about the focal domain of GM food was even influenced by him expressing a congruent attitude in an unrelated domain. This result supports a general similarity account of the congruence effect on trust, as opposed to a confirmatory bias account.
