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Differences between mates at the TLR1Lb locus are associated with lower reproductive success in a long-lived seabird.
Sci Rep
December 2024
Department of Biology, Queen's University, Kingston, ON, Canada.
Genetic diversity can influence fitness components such as survival and reproductive success. Yet the association between genetic diversity and fitness based on neutral loci is sometime very weak and inconsistent, with relationships varying among taxa due to confounding effects of population demography and life history. Fitness-diversity relationships are likely to be stronger and more consistent for genes known to influence phenotypic traits, such as immunity-related genes, and may also depend on the genetic differences between breeding partners.
View Article and Find Full Text PDFBacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity.
Nat Commun
December 2024
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
The genomes of human gut bacteria in the genus Bacteroides include numerous operons for biosynthesis of diverse capsular polysaccharides (CPSs). The first two genes of each CPS operon encode a locus-specific paralog of transcription elongation factor NusG (called UpxY), which enhances transcript elongation, and a UpxZ protein that inhibits noncognate UpxYs. This process, together with promoter inversions, ensures that a single CPS operon is transcribed in most cells.
View Article and Find Full Text PDFRobust and inducible genome editing via an all-in-one prime editor in human pluripotent stem cells.
Nat Commun
December 2024
The SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY, USA.
Prime editing (PE) allows for precise genome editing in human pluripotent stem cells (hPSCs), such as introducing single nucleotide modifications, small insertions or deletions at a specific genomic locus. Here, we systematically compare a panel of prime editing conditions in hPSCs and generate a potent prime editor, "PE-Plus", through co-inhibition of mismatch repair and p53-mediated cellular stress responses. We further establish an inducible prime editing platform in hPSCs by incorporating the PE-Plus into a safe-harbor locus and demonstrated temporal control of precise editing in both hPSCs and differentiated cells.
View Article and Find Full Text PDFNon-APOE variants predominately expressed in smooth muscle cells contribute to the influence of Alzheimer's disease genetic risk on white matter hyperintensities.
Alzheimers Dement
December 2024
Department of Psychology, University of Bath, Bath, UK.
Introduction: White matter hyperintensity volumes (WMHVs) are disproportionally prevalent in individuals with Alzheimer's disease (AD), potentially reflecting neurovascular injury. We quantify the association between AD polygenic risk score (AD-PRS) and WMHV, exploring single-nucleotide polymorphisms (SNPs) that are proximal to genes overexpressed in cerebrovascular cell species.
Methods: In a UK-Biobank sub-sample (mean age = 64, range = 45-81 years), we associate WMHV with (1) AD-PRS estimated via SNPs across the genome (minus apolipoprotein E [APOE] locus) and (2) AD-PRS estimated with SNPs proximal to specific genes that are overexpressed in cerebrovascular cell species.
Heterodisomy in the locus is also a cause of pseudohypoparathyroidism type 1B (iPPSD3).
Front Endocrinol (Lausanne)
December 2024
Rare Disease Research Group, Molecular (Epi) Genetics Laboratory, Bioaraba Health Research Institute, Araba University Hospital, Vitoria-Gasteiz, Spain.
Objective: To identify the genetic cause underlying the methylation defect in a patient with clinical suspicion of PHP1B/iPPSD3.
Design: Imprinting is an epigenetic mechanism that allows the regulation of gene expression. The locus is one of the loci within the genome that is imprinted.
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