Pinpointing culprit causal variants along signal peaks of genomewide association studies (GWAS) is challenging. To overcome confounding effects of multiple independent variants at such a locus and narrow the interval for causal allele capture, we developed an approach that maps local shared haplotypes harboring a putative causal variant. We demonstrate our method in an extreme isolate founder population, the pacific Island of Kosrae. We analyzed plasma plant sterol (PPS) levels, a surrogate measure of cholesterol absorption from the intestine, where previous studies have implicated 2p21 mutations in the ATP binding cassette subfamily G members 5 or 8 (ABCG5 or ABCG8) genes. We have previously reported that 11.1% of the islanders are carriers of a frameshift ABCG8 mutation increasing PPS levels in carriers by 50%. GWAS adjusted for this mutation revealed genomewide significant signals along 11 Mb around it. To fine-map this signal, we detected pairwise identity-by-descent haplotypes using our tool GERMLINE and implemented a clustering algorithm to identify haplotypes shared across multiple samples with their unique shared boundaries. A single 526-kb haplotype mapped strongly to PPS levels, dramatically refining the mapped interval. This haplotype spans the ABCG5/ABCG8 genes, is carried by 1.8% of the islanders, and results in a striking 100% increase of PPS in carriers. Resequencing of ABCG5 in these carriers found a D450H missense mutation along the associated haplotype. These findings exemplify the power of haplotype analysis for mapping mutations in isolated populations and specifically for dissecting effects of multiple variants of the same locus.genetics ͉ genomewide association study ͉ haplotype mapping ͉ plasma plant sterols R apid technological advances in genomics over the last few years have focused on identifying common genetic variants affecting complex disease risk. To date genome-wide association studies (GWAS) have reproducibly implicated over 270 genomic regions that modify the risk for over 70 complex disease and health-related phenotypes (1-3). However, identifying the culprit causal variant underlying these local peaks in association signals remains a challenging task with only a handful of causal variants identified so far (4 -6). One conventional approach is sequencing a region of arbitrary length around the signal peak across enough individuals to capture the causal allele. However, the larger the sequenced interval and number of individuals, the more variants discovered making it difficult to distinguish the driver allele from the large number of passenger variants. This problem is exacerbated in cases where multiple, seemingly independent signals reside in close proximity along the genome. Recent examples of multiple alleles include the 8q24 region for prostate cancer (7-9), 6p21 region for HIV-1 viral setpoint (10), the IL23R, 6p25, and 17q21 regions for Crohn's disease (11, 12), the PNPLA3 region and nonalcoholic fatty liver disease (13), the IRF5, STAT4, and TNFAIP3 regions for systemic...
The rapid inclusion of online assessment in higher education has left a void in investigating the relationship this form of assessment has with student emotions. This study examines the influence of frequent online assessment on student emotions in a university setting using a mixed-methods approach. Students' emotions in an online quiz and a traditional classroom test in a second-year mathematics course (n = 91) were analysed using both quantitative and qualitative approaches, through the lens of the control-value theory. The study used an adaptation of the Achievement Emotions Questionnaire (AEQ) to collect data on reported student emotions in both assessments, as well as qualitative data on student’s views of the frequent online assessment. Students reported higher levels of positive emotions and lower levels of negative emotions in an online quiz compared to the test, and we attempted to identify sources of these differences. The findings are discussed together with implications for habitualisation of assessment emotions. Practically grounded generalisations are outlined as opportunities for disrupting negative emotions and reaffirming positive emotions, which are suitable for implementation in higher education on a broad scale. Implications for practice or policy: For educators designing tertiary assessment aimed at promoting positive and reducing negative emotions, we advise incorporating features that students perceive as allowing them greater control over obtaining success. Specifically, we advise incorporating frequent low stakes online quizzes into tertiary courses. These present opportunities for students to habitualise positive assessment-related emotions, which correlate with performance and constructs such as self-efficacy. The Achievement Emotions Questionnaires (AEQ) can be adapted to investigate achievement emotions in different forms of assessment.
<p style='text-indent:20px;'>Emotions are an integral part of problem-solving, but must emotions traditionally conceptualised as "negative" have negative consequences in learning? Frustration is one of the most prominent emotions reported during mathematical problem-solving across all levels of learning. Despite research aiming to mitigate frustration, it can play a positive role during mathematical problem solving. A systematic review method was used to explore how frustration usually appears in students during mathematical problem-solving and the typical patterns of emotions, behaviours, and cognitive processes that are associated with its occurrence. The findings are mixed, which informs the need for further research in this area. Additionally, there are theories and qualitative findings about the potential positive role of frustration that have not been followed up with empirical investigations, which illuminate how our findings about negative emotions may be limited by the questions we ask as researchers. With the support of research, I consider how educators may directly or indirectly address rethinking the role and consequences of frustration during problem-solving with their students.</p>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.