Founder populations are of special interest to both evolutionary and conservation biologists, but the detection of genetic signals of selection in these populations is challenging due to their demographic history. Geographically separated founder populations likely to have been subjected to similar selection pressures provide an ideal but rare opportunity to overcome these challenges. Here we take advantage of such a situation generated when small, isolated founder populations of reindeer were established on the island of South Georgia, and using this system we look for empirical evidence of selection overcoming strong genetic drift. We generated a 70 k ddRADseq single nucleotide polymorphism database for the two parallel reindeer founder populations and screened for signatures of soft sweeps. We find evidence for a genomic region under selection shared among the two populations, and support our findings with Wright-Fisher model simulations to assess the power and specificity of interpopulation selection scans-namely Bayescan, OutFLANK, PCadapt and a newly developed scan called Genome Wide Differentiation Scan (GWDS)-in the context of pairwise source-founder comparisons. Our simulations indicate that loci under selection in small founder populations are most probably detected by GWDS, and strengthen the hypothesis that the outlier region represents a true locus under selection. We explore possible, relevant functional roles for genes in linkage with the detected outlier loci.
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Introduction: GNE-myopathy is a distal myopathy with adult-onset and initial involvement of anterior leg compartment. A founder effect has been demonstrated for some patients from several large cohorts in different countries.
Methods: In this study, we investigated the allele frequency of the c.
Mechanobiol Med
December 2024
Department of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USA.
Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using or strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive.
View Article and Find Full Text PDFNat Biomed Eng
December 2024
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors.
View Article and Find Full Text PDFJ Med Genet
December 2024
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
Background: The NHS Jewish BRCA Testing Programme is offering germline and genetic testing to people with ≥1 Jewish grandparent. Who have an increased likelihood of having an Ashkenazi Jewish (AJ) founder germline pathogenic variant (gPV) compared with the general population.Testing is offered via a self-referral, home-based saliva sampling pathway, supported by a genetic counsellor telephone helpline.
View Article and Find Full Text PDFPLoS Pathog
December 2024
Institute of Human Genetics, School of Medicine, University Bonn & University Hospital Bonn, Bonn, Germany.
Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.
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