ABSTRACT
Newborn screening programs are an integral part of public health systems aiming to save lives and improve the quality of life for infants with treatable disorders. Technological advancements have driven the expansion of newborn screening programs in the last two decades and the development of fast, accurate next-generation sequencing technology has opened the door to a range of possibilities in the field. However, technological challenges with short-read next-generation sequencing technologies remain significant in highly homologous genomic regions such as pseudogenes or paralogous genes and need to be considered when implemented in screening programs. Here, we simulate 50 genomes from populations around the world to test the extent to which high homology regions affect short-read mapping of genes related to newborn screening disorders and the impact of differential read lengths and ethnic backgrounds. We examine a 158 gene screening panel directly relevant to newborn screening and identify gene regions where read mapping is affected by homologous genomic regions at different read lengths. We also determine that the patient's ethnic background does not have a widespread impact on mapping accuracy or coverage. Additionally, we identify newborn screening genes where alternative forms of sequencing or variant calling pipelines should be considered and demonstrate that alterations to standard variant calling can retrieve some formerly uncalled variants.
ABSTRACT
It has been suggested that mental states play an important role in determining behaviour and that mental state attributions ("theory of mind") underlie the ability to understand and predict other peoples' behaviour. Theory of mind was investigated in 31 patients with unilateral frontal lobe lesions (15 right-sided and 16 left-sided) by comparing their performance with that of 31 matched control subjects. The ability to infer first- and second-order beliefs was tested by requiring subjects to listen to stories in which a protagonist acted upon a false belief. Both patient groups exhibited significantly impaired performance on the two theory of mind measures. Both frontal lobe groups also exhibited a range of deficits in tests of executive functions, but analyses revealed that these seemed to be independent of theory of mind impairments. These findings are discussed in terms of the hypothesis of a specialized, adaptive brain system underlying theory of mind reasoning ability, and are related to observed difficulties in social functioning among patients with frontal lobe damage.
