Biology subjects

Paschall, J.

Publications and source records attributed to Paschall, J..

5 recordsLinked to original sources

bioRxiv2026

Genetic and Epigenetic Landscape of Self-Identified Hispanics/Latino in All Of Us

Human genetic studies still underrepresent many populations, limiting discovery and interpretation of medically relevant variation. Extensive admixture in self-identified Hispanic/Latino populations increases the need for representative reference data and ancestry-aware interpretation of medically relevant variation. We used long-read sequencing to analyze genetic variation, ancestry, and DNA methylation in 1,490 self-identified Hispanic/Latino participants from the All of Us Research Program. We identified 10 million novel variants and more than 100 candidate phenotype associations, with fine-mapping prioritizing structural variants over nearby single-nucleotide variants in more than half. We linked 3,329 tandem repeats to DNA methylation, resolved widespread allele-specific methylation, and identified ancestry-linked regulation across paralogous genes. These results reveal previously inaccessible genetic and regulatory variation and show the value of long-read sequencing for diverse populations.

genetics↗

bioRxiv2026

Biobank-scale genotyping of Robertsonian translocations reveals hidden structural variation on the human acrocentric chromosomes

Balanced Robertsonian translocation (ROB) is the most common chromosomal rearrangement in humans, with an estimated occurrence of 1 in 800 in newborn studies. Carriers are at increased risk of cancer and often diagnosed at fertility clinics after facing recurrent miscarriages, infertility, or aneuploid offspring. Genotyping carriers with DNA sequencing has been challenging because of gaps and misrepresentation of the translocation fusion site in the human reference genome. Only recently, telomere-to-telomere (T2T) human genomes successfully revealed sequences of the acrocentric short arms, including the most common ROB fusion site. A ROB results in loss of two ribosomal DNA (rDNA) arrays and its adjacent distal sequences, including the highly conserved distal junction (DJ). Here, we present a novel method to type ROB carriers directly from short sequencing reads by estimating DJ copy number. We demonstrate that our method successfully genotypes ROBs using a reference-free approach or alignments to either T2T-CHM13v2 or GRCh38. Applying the method to a cohort of healthy newborns and family members (n=4,172) as well as the UK Biobank (n=490,416), we find candidate ROBs at a frequency consistent with the previously reported 1 in 800 incidence (0.11-0.12%). In addition to ROB carriers, we report the frequency of one DJ loss (9, 2.8-3.4%) or gain (11+, 8.4-9.3%) from the two cohorts and the 1000 Genomes Project (n=3,202), and characterize the underlying structural variation in near-T2T genome assemblies from the Human Pangenome Reference Consortium. Importantly, our method provides the first sequencing-based diagnostic for Robertsonian chromosomes and can be applied to low-coverage sequencing data, enhancing its clinical applicability and enabling new studies of structural variation on the acrocentric chromosomes.

genomics↗

bioRxiv2022

A chromosome-length assembly of the Hawaiian Monk seal (Neomonarchus schauinslandi) confirms genomic stability in the Pinnipeds and a prolonged history of "genetic purging"

The Hawaiian monk seal (HMS) is the single extant species of tropical earless seals of the genus Neomonachus. The species survived a severe bottleneck in the late 19th century and experienced subsequent population declines until becoming the subject of a NOAA-led species recovery effort beginning in 1976 when the population was fewer than 1000 animals. Like other recovering species, the Hawaiian monk seal has been reported to have reduced genetic heterogeneity due to the bottleneck and subsequent inbreeding. Here we report a chromosomal reference assembly for a male animal produced using a variety of methods including linked-read sequencing, Hi-C contiguity mapping, optical genome mapping, and nanopore long read sequencing. The final assembly consisted of 16 autosomes, an X and portions of the Y chromosomes. We compared variants in the reference animals to nine other HMS and to the human reference NA12878 confirming a low level of variation within the species and one-eighth that of the human reference. A lack of variation in several MHC genes was documented suggesting that this species may be at risk for infectious disease. Lastly, the HMS chromosomal assembly confirmed significant synteny with other pinnipeds. This reference should be a useful tool for long-term management of HMS and evolutionary studies of other carnivorans.

genomics↗

bioRxiv2022

XY sex determination in a cnidarian

Sex determination occurs across animal species, but most of our knowledge about the mechanisms of sex determination comes from only a handful of bilaterian taxa. This limits our ability to infer the evolutionary history of sex determination within animals. In this study, we generated a linkage map of the genome of the colonial cnidarian Hydractinia symbiolongicarpus and used this map to determine that this species has an XX/XY sex determination system. We delineate the pseudoautosomal and non-recombining regions of the Y chromosome and show that the latter encodes a number of genes with male gonad-specific expression. These findings establish Hydractinia as a tractable non-bilaterian model system for the study of sex determination. Significance StatementWhat determines whether an animal is male or female? The answer depends on the species. Some rely on signals from their environment, while others take cues from their genome. Most of what we understand about sex determination comes from traditional model organisms (such as mice, flies, and worms) or groups of well-studied vertebrates and insects. Studying sex determination in other animals, especially those from phyla that diverged early in animal evolution, would allow us to better understand how sex has evolved across the animal kingdom and could reveal pathways present in the eumetazoan ancestor >600 million years ago. In this study, we show that the cnidarian Hydractinia symbiolongicarpus has XY sex determination, establishing this species as a model system for sex determination in an understudied group of animals.

genetics↗

bioRxiv2018

Mango: Distributed Visualization for Genomic Analysis

The decreasing cost of DNA sequencing over the past decade has led to an explosion of available sequencing datasets, leaving us with terabytes to petabytes of data to explore and analyze. It is critical for analysts in research and clinical settings to be able to develop new data-driven hypotheses from these datasets through bias identification, analysis of data quality, and testing different algorithms and parameter settings. However, current interactive tools for sequence analysis are designed to run on single machines that do not scale to the size of modern genomic datasets, and rely on precomputed static views, rather than allowing direct interaction with the primary dataset. Mango is a genomic sequence visualization and analysis platform that removes these constraints regarding scalability and staticity by leveraging the power of multi-node compute clusters in the cloud to allow interactive analysis over terabytes of sequencing data. Mango provides both a genome browser graphical user interface and programmable notebook form factor to allow users of varying analytical experience to explore large sequencing datasets on both private clusters and in the cloud. These tools provide a flexible environment for interactive exploration of genomic datasets, while surpassing the computational limits of single-node genomic visualization tools.

bioinformatics↗