Biology subjects

Cheung, W.

Publications and source records attributed to Cheung, W..

5 recordsLinked to original sources

bioRxiv2025

Long-read sequencing reveals telomere inheritance patterns from human trios

Telomeres are essential for maintaining genomic integrity and are associated with cellular aging and disease, yet the factors influencing their inheritance across generations remain poorly understood. Leveraging PacBio HiFi long-read sequencing and 75 parent-offspring trios (n = 225) from the Genomic Answers for Kids program, we analyzed individual telomeres across chromosomes and their inheritance. Telomere length (TL) varied between chromosome arms in a way that was consistent in parents and offsprings, with average values ranging from 5000 to 8000 base pairs. Maternal and paternal TL together were a strong predictor of child TL (R2 = 0.59). Notably, using telomeric variant repeats, we developed a tool that enabled allelic tracing for 53.3% of maternally and 49.9% of paternally inherited telomeres. In the child, paternally transmitted alleles were significantly longer than age-matched maternal ones ({Delta}mean = 409 bp, p = 2.6e-05), particularly when from older parents ({Delta}mean = 698 bp, p = 8.9e-05) and at chromosome arms with shorter average TL ({Delta}mean = 752 bp, p = 1.6e-06). These findings reveal parent-of-origin effects and heritable influences on TL, providing novel insights into telomere dynamics and their potential implications in age-related disease susceptibility.

genetics↗

bioRxiv2023

Multiple Pleistocene refugia for Arctic White Heather (Cassiope tetragona) supported by population genomics analyses of contemporary and Little-Ice-Age samples

AimArctic plants survived the Pleistocene glaciations in unglaciated refugia, but the number of these refugia is often unclear. We use high-resolution genomic data from present-day and Little-Ice-Age populations of Arctic White Heather (Cassiope tetragona) to re-evaluate the biogeography of this species and determine whether it had multiple independent refugia or a single refugium in Beringia. LocationCircumpolar Arctic and Coastal British Columbia (BC) alpine TaxonCassiope tetragona L., subspecies saximontana and tetragona, outgroup C. mertensiana (Ericaceae) MethodsWe built genotyping-by-sequencing (GBS) libraries using Cassiope tetragona tissue from 36 Arctic locations, including two [~]250-500-year-old populations collected under glacial ice on Ellesmere Island, Canada. We assembled a de novo GBS reference and called variants in dDocent. Population structure, genetic diversity, and demography were inferred from PCA, ADMIXTURE, fastsimcoal2, SplitsTree, and several population genomics statistics. ResultsPopulation structure analyses identified 4-5 clusters that align with geographic locations. Nucleotide diversity was highest in Beringia and decreased eastwards across Canada. Demographic coalescent analysis of the site-frequency-spectrum dated the following splits from Alaska: BC subspecies saximontana (6 mya), Russia (1.5 mya), Europe (>300-600 kya), Greenland (100 kya). Northern Canada populations appear to be from the current interglacial (7-9 kya). Genetic variants from Alaska appeared more frequently in present-day than historic plants on Ellesmere Island. ConclusionsDemographic analyses show BC, Alaska, Russia, Europe, and Greenland all had separate refugia during the last major glaciations. Northern Canadian populations appear to be founded during the current interglacial with genetic contributions from Alaska, Europe, and Greenland. On Ellesmere Island, there is evidence for continued, recent gene flow with foreign variants introduced in the last 250-500 years. These results suggest that a re-analysis of other Arctic species with shallow population structure using higher resolution genomic markers and demographic analyses may help reveal deeper structure and other circumpolar glacial refugia.

genomics↗

bioRxiv2022

Sentinel Cards Provide Practical SARS-CoV-2 Monitoring in School Settings

Accurate, high-resolution environmental monitoring of SARS-CoV-2 traces indoors through sentinel cards is a promising approach to help students safely return to in-person learning. Because SARS-CoV-2 RNA can persist for up to a week on several indoor surface types, there is a need for increased temporal resolution to determine whether consecutive surface positives arise from new infection events or continue to report past events. Cleaning sentinel cards after sampling would provide the needed resolution, but might interfere with assay performance. We tested the effect of three cleaning solutions (BZK wipes, wet wipes, RNase Away) at three different viral loads: "high" (4 x 104 GE/mL), "medium" (1 x 104 GE/mL), and "low" (2.5 x 103 GE/mL). RNAse Away, chosen as a positive control, was the most effective cleaning solution on all three viral loads. Wet wipes were found to be more effective than BZK wipes in the medium viral load condition. The low viral load condition was easily reset with all three cleaning solutions. These findings will enable temporal SARS-CoV-2 monitoring in indoor environments where transmission risk of the virus is high and the need to avoid individual-level sampling for privacy or compliance reasons exists. ImportanceBecause SARS-CoV-2, the virus that causes COVID-19, persists on surfaces, testing swabs taken from surfaces is useful as a monitoring tool. This approach is especially valuable in school settings, where there are cost and privacy concerns that are eliminated by taking a single sample from a classroom. However, the virus persists for days to weeks on surface samples, so it is impossible to tell whether positive detection events on consecutive days are persistent signal or new infectious cases, and therefore whether the positive individuals have been successfully removed from the classroom. We compare several methods for cleaning "sentinel cards" to show that this approach can be used to identify new SARS-CoV-2 signals day to day. The results are important for determining how to monitor classrooms and other indoor environments for SARS-CoV-2 virus.

bioinformatics↗

bioRxiv2021

Comparison of heat-inactivated and infectious SARS-CoV-2 across indoor surface materials shows comparable RT-qPCR viral signal intensity and persistence

Environmental monitoring in public spaces can be used to identify surfaces contaminated by persons with COVID-19 and inform appropriate infection mitigation responses. Research groups have reported detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on surfaces days or weeks after the virus has been deposited, making it difficult to estimate when an infected individual may have shed virus onto a SARS-CoV-2 positive surface, which in turn complicates the process of establishing effective quarantine measures. In this study, we determined that reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection of viral RNA from heat-inactivated particles experiences minimal decay over seven days of monitoring on eight out of nine surfaces tested. The properties of the studied surfaces result in RT-qPCR signatures that can be segregated into two material categories, rough and smooth, where smooth surfaces have a lower limit of detection. RT-qPCR signal intensity (average quantification cycle (Cq)) can be correlated to surface viral load using only one linear regression model per material category. The same experiment was performed with infectious viral particles on one surface from each category, with essentially identical results. The stability of RT-qPCR viral signal demonstrates the need to clean monitored surfaces after sampling to establish temporal resolution. Additionally, these findings can be used to minimize the number of materials and time points tested and allow for the use of heat-inactivated viral particles when optimizing environmental monitoring methods. ImportanceEnvironmental monitoring is an important tool for public health surveillance, particularly in settings with low rates of diagnostic testing. Time between sampling public environments, such as hospitals or schools, and notifying stakeholders of the results should be minimal, allowing decisions to be made towards containing outbreaks of coronavirus disease 2019 (COVID-19). The Safer At School Early Alert program (SASEA) [1], a large-scale environmental monitoring effort in elementary school and child care settings, has processed > 13,000 surface samples for SARS-CoV-2, detecting viral signals from 574 samples. However, consecutive detection events necessitated the present study to establish appropriate response practices around persistent viral signals on classroom surfaces. Other research groups and clinical labs developing environmental monitoring methods may need to establish their own correlation between RT - qPCR results and viral load, but this work provides evidence justifying simplified experimental designs, like reduced testing materials and the use of heat-inactivated viral particles.

microbiology↗

bioRxiv2019

Massive haplotypes underlie ecotypic differentiation in sunflowers

Species often include multiple ecotypes that are adapted to different environments. But how do ecotypes arise, and how are their distinctive combinations of adaptive alleles maintained despite hybridization with non-adapted populations? Re-sequencing of 1506 wild sunflowers from three species identified 37 large (1-100 Mbp), non-recombining haplotype blocks associated with numerous ecologically relevant traits, and soil and climate characteristics. Limited recombination in these regions keeps adaptive alleles together, and we find that they differentiate several sunflower ecotypes; for example, they control a 77 day difference in flowering between ecotypes of silverleaf sunflower (likely through deletion of a FLOWERING LOCUS T homolog), and are associated with seed size, flowering time and soil fertility in dune-adapted sunflowers. These haplotypes are highly divergent, associated with polymorphic structural variants, and often appear to represent introgressions from other, possibly extinct, congeners. This work highlights a pervasive role of structural variation in maintaining complex ecotypic adaptation.

evolutionary biology↗