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Most genome-wide association studies (GWASs) of depression focus on broad, heterogeneous outcomes, limiting the discovery of genomic risk loci specific to major depressive disorder (MDD). Previous UK Biobank (UKB) studies had limited ability to pinpoint MDD-associated loci due to a smaller sample with strictly defined MDD outcomes and further exclusion of many participants based on ancestry or relatedness, significantly underutilizing this resource's potential for elucidating the genetic architecture of MDD. Here, we present novel genomic insights into MDD by fully utilizing existing UKB data through (1) a trans-ancestry GWAS pipeline using two complementary approaches controlling for population structure and relatedness and (2) an increased sample with MDD symptom-level data across two mental health assessments.
View Article and Find Full Text PDFSpecies trees need to be dated for many downstream applications. Typical molecular dating methods take a phylogenetic tree with branch lengths in substitution units as well as a set of calibrations as input and convert the branch lengths of the species tree to the unit of time while being consistent with the pre-specified calibrations. When dating species trees from multi-locus genome-scale datasets, the branch lengths and sometimes the topology of the species tree are estimated using concatenation.
View Article and Find Full Text PDFVariant ribosomal DNA is essential for female differentiation in zebrafish.
Philos Trans R Soc Lond B Biol Sci
March 2025
University of Otago, Dunedin 9054, New Zealand.
The ribosome consists of protein and RNA components. Deletion of genes encoding specific ribosomal proteins has revealed that heterogeneity in the ribosome must exist in vertebrates; however, this has not been tested for ribosomal RNA (rRNA). In zebrafish (), the '45S-M' ribosomal RNA-encoding locus undergoes massive extrachromosomal amplification during oocyte growth and ovary differentiation and is distinct from the regular ribosomal DNA (rDNA) locus encoding somatic rRNA (45S-S).
View Article and Find Full Text PDFUnlabelled: Phylogenetic branch lengths are essential for many analyses, such as estimating divergence times, analyzing rate changes, and studying adaptation. However, true gene tree heterogeneity due to incomplete lineage sorting (ILS), gene duplication and loss (GDL), and horizontal gene transfer (HGT) can complicate the estimation of species tree branch lengths. While several tools exist for estimating the topology of a species tree addressing various causes of gene tree discordance, much less attention has been paid to branch length estimation on multi-locus datasets.
View Article and Find Full Text PDFPan-cancer multi-omic model of LINE-1 activity reveals locus heterogeneity of retrotransposition efficiency.
Nat Commun
February 2025
Halvorsen Center for Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Somatic mobilization of LINE-1 (L1) has been implicated in cancer etiology. We analyzed a recent TCGA data release comprised of nearly 5000 pan-cancer paired tumor-normal whole-genome sequencing (WGS) samples and ~9000 tumor RNA samples. We developed TotalReCall an improved algorithm and pipeline for detection of L1 retrotransposition (RT), finding high correlation between L1 expression and "RT burden" per sample.
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