A major mechanism for the generation allelic diversity in the Plasmodium falciparum msp1 gene is meiotic recombination in the Anopheles mosquito. The frequency of recombination events is dependent on the intensity of transmission. Herein we investigate the frequency of recombination-driven allelic diversity and temporal variation of msp1 in Rufiji, eastern coastal Tanzania, where malaria transmission is intense. We identified 5' recombinant types, 3' sequence types, and msp1 haplotypes (unique associations of 5' recombinant types and 3' sequence types) to measure the extent and temporal variation of msp1 allelic diversity. The results show that msp1 haplotype diversity is higher in Tanzania as compared with areas with lower transmission rates. The frequencies of individual polymorphic regions/sites remained stable during the study period. However, the frequency distribution of msp1 haplotypes varied between 1993 and 1998. These results suggest that frequent recombination events between msp1 alleles intermittently generate novel alleles in high transmission areas.
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Epilepsia
January 2025
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
Objective: Somatic variants causing epilepsy are challenging to detect, as they are only present in a subset of brain cells (e.g., mosaic), resulting in low variant allele frequencies.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
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December 2024
Boston Children's Hospital, Boston, MA, USA.
Background: Alzheimer's disease (AD), an age-associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid-β and tau. While neuroinflammation, mediated by microglia and brain-resident macrophages, plays a pivotal role in AD pathogenesis, the intricate interactions among age, genes, and other risk factors remain elusive. Somatic mutations, known to accumulate with age, instigate clonal expansion across diverse cell types, impacting both cancer and non-cancerous conditions.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Departments of Psychiatry and Behavioral Sciences, Neurology, and Epidemiology, University of California San Francisco, San Francisco, CA, USA.
Background: Integrating clinical and genetic risk factors for dementia in a precision medicine framework can play a crucial role in primary prevention. Here, we ascertained the proportion of individuals who are at heightened risk of developing dementia based on their family history, genetic, and clinical risk factors and evaluated how the additive burden of these risk indicators is associated with incident dementia.
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Alzheimers Dement
December 2024
Yale School of Medicine, New Haven, CT, USA.
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