Biology subjects

Ahmed, A.

Publications and source records attributed to Ahmed, A..

90 records · Page 5Linked to original sources

bioRxiv2020

The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection. The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex protein in silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft corals Sinularia flexibilis and Phaius mishmensis may have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.

bioinformatics↗

bioRxiv2020

Neurotrophic Factor-Laden Acellular Chondroitin Sulfate Scaffolds Promote Chronic Functional Recovery After Severe Traumatic Brain Injury

Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brains poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely post-sTBI, significantly enhanced cellular repair and gross motor function recovery when compared to controls, 20 weeks post-sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations, demonstrated the significant recovery of reach-to-grasp function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely post-sTBI can support complex cellular, vascular, and neuronal circuit repair, chronically after sTBI.

bioengineering↗

bioRxiv2020

Microengineered three-dimensional collagen landscapes with independently tunable fiber anisotropy and directionality

Fibrillar collagens are structural proteins in the extracellular matrix (ECM), and cellular processes, including differentiation, proliferation, and migration, have been linked to the orientation (directionality) and alignment (anisotropy) of collagen fibers. Given the importance of cell-substrate interactions in driving biological functions, several microfluidic approaches have demonstrated three-dimensional (3D) collagen gels with defined fiber properties that enable quantitative correlations between structural cues and observed cell responses. Although existing methods provide excellent definition over collagen fiber anisotropy, independent control over both anisotropy and directionality (that we collectively refer to as the collagen landscape) has not been demonstrated. Therefore, to advance collagen microengineering capabilities, we present a user-friendly approach that uses controlled fluid flows within a non-uniform microfluidic channel network to create well-defined collagen landscapes. We demonstrate capabilities including i) control over fiber anisotropy, ii) spatial gradients in fiber anisotropy, iii) defined fiber directionality, and iv) multi-material interfaces. We then show that cells respond to the microengineered topographic cues by aligning along the anisotropy domains and following fiber directionality. Finally, this platforms modular capability is demonstrated by integrating an ultrathin porous parylene (UPP) membrane on the microengineered collagen as a mask to control cell-substrate interactions.

bioengineering↗

bioRxiv2020

Age-induced methylmalonic acid accumulation promotes tumor progression and aggressiveness

From age 65 onwards, the risk of cancer incidence and associated mortality is substantially higher1-3. Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy4. For decades, the link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the well-established role of diet, exercise and small molecules that target the pace of metabolic aging5-8. Here, we show that metabolic alterations that occur with age can render a systemic environment favorable to progression and aggressiveness of tumors. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is significantly up-regulated in the serum of older people, and functions as a mediator of tumor progression. We traced this to the induction of SOX4 and a consequent transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, accumulation of MMA represents a novel link between aging and cancer progression, implicating MMA as a novel therapeutic target for advanced carcinomas.

cancer biology↗

bioRxiv2020

Biochemical profile and bioactive potential of wild folk medicinal plants of Zygophyllaceae from Balochistan, Pakistan.

Recent focus is on analysis of biological activities of extracts from plant species. Zygophyllaceae is exceedingly important angiosperm family with many taxa being used in folk medicines widely dispersed in arid and semi-arid zones of Balochistan, Pakistan. Only a small proportion of them have been scientifically analyzed and many species are nearly facing extinction. Therefore present investigation explores the biochemical and bioactive potential of fourteen folk medicinal plants usually used for treatments of different ailments. Fresh aerial parts of nine taxa and two fruit samples were collected from plants growing in arid and semi-arid zones of Balochistan and analyzed for enzymatic, non-enzymatic and other biochemical activities. Higher phytochemical activities were detected in the aerial parts. Superoxide dismutase was detected maximum in Fagonia indica, (184.7{+/-}5.17 units/g), ascorbate peroxidase in Tribulus longipetalus subsp. longipetalus (947.5{+/-}12.5 Units/g), catalase and peroxidase was higher in Peganum harmala (555.0{+/-}5.0 and 2597.8{+/-}0.4 units/g respectively). Maximum esterase and alpha amylase activity was found in Zygophyllum fabago (14.3{+/-}0.44 and 140{+/-}18.8 mg/g respectively). Flavonoid content was high in T. longipetalus subsp. longipetalus (666.1{+/-}49 g/ml). The highest total phenolic content and tannin was revealed in F. olivieri (72125{+/-}425 and 37050{+/-}1900 M/g. respectively). Highest value of ascorbic acid was depicted in F. bruguieri var. rechingeri (448{+/-}1.5 g/g). Total soluble Proteins and reducing sugars were detected higher in P. harmala (372.3{+/-}54 and 5.9{+/-}0.1 mg/g respectively). Maximum total antioxidant capacity (TAC) was depicted in Z. simplex (16.9{+/-}0.01 M/g). Pigment analysis exhibited the high value of lycopene and total carotenoids in T. terrestris (7.44{+/-}0.2 and 35.5{+/-}0.0 mg/g respectively). Chlorophyll a, b and total chlorophyll content was found maximum in T. longipetalus subsp. pterophorus (549.1{+/-}9.9, 154.3{+/-}10 and 703.4{+/-}20.2 ug/g respectively). All taxa exhibited anti-inflammatory activity as well as anti-diabetic inhibitory potential. Seed extracts of Zygophyllum eurypterum (96%) exhibited highest inhibitory potential, along with twelve other taxa of Zygophyllaceae indicated (96-76%) activity when compared with the standard drug diclofenac sodium (79%). Seeds of T. longipetalus subsp. longipetalus (85%) exhibited the highest anti-diabetic activity; other eleven taxa also exhibited inhibitory activity of -amylase ranging from (85-69%) compared with Metformin (67%) standard drug. Phytochemical screening revealed that selected taxa proved to be the potential source of natural antioxidants and could further be explored for in-vivo studies and utilized in pharmaceutical industries as potent therapeutic agents validating their ethno-pharmacological uses.

plant biology↗

bioRxiv2020

Alterations in Acylcarnitines, Amines, and Lipids Inform about Mechanism of Action of Citalopram/Escitalopram in Major Depression

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium- and long-chain acylcarnitines, suggesting an SSRI effect on {beta}-oxidation and mitochondrial function. Amines - including arginine, proline, and methionine-sulfoxide - were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17[≤]7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine and serotonin; and b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2 and PC aa C36:4. These findings suggest that mitochondrial energetics - including acylcarnitine metabolism, transport and its link to {beta}-oxidation - and lipid membrane remodeling may play roles in SSRI treatment response.

neuroscience↗

bioRxiv2020

Age dependent changes in synaptic NMDA receptor composition in adult human cortical neurons

The molecular processes underlying the ageing-related decline in cognitive performance and memory observed in humans are poorly understood. Studies in rodents have shown a decrease in N-methyl-D-aspartate receptors (NMDARs) that contain the GluN2B subunit in ageing synapses, and this decrease is correlated with impaired memory functions. However, the age-dependent contribution of GluN2B containing receptors to synaptic transmission in human cortical synapses has not been previously studied. We investigated the synaptic contribution of GluN2A and GluN2B containing NMDARs in adult human neurons using fresh non-pathological temporal cortical tissue resected during neurosurgical procedures. The tissue we obtained fulfilled quality criteria by the absence of inflammation markers and proteomic degradation. We show an age-dependent decline in the NMDA/AMPA receptor ratio in adult human temporal cortical synapses. We demonstrate that GluN2B containing NMDA receptors contribute to synaptic responses in the adult human brain with a reduced contribution in older individuals. With previous evidence demonstrating the critical role of synaptic GluN2B in regulating synaptic strength and memory storage in mice, this progressive reduction of GluN2B in the human brain during ageing may underlie a molecular mechanism in the age-related decline in cognitive abilities and memory observed in humans.

neuroscience↗

bioRxiv2019

Is the rat prefrontal cortex crucial for cognitive control during spatial cognition?

Cognitive control tasks require using one class of information while ignoring competing classes of information. The central role of the medial prefrontal cortex (mPFC) in cognitive control is well established in the primate literature, and largely accepted in the rodent literature because mPFC damage causes deficits in tasks that may require cognitive control, as inferred, typically from the task design. In prior work, we used an active place avoidance task where a rat or mouse on a rotating arena is required to avoid the stationary task-relevant locations of a mild shock and ignore the rotating task-irrelevant locations of those shocks. The task is impaired by hippocampal manipulations, and the discharge of hippocampal place cell populations judiciously alternates between representing stationary locations near the shock zone and rotating locations far from the shock zone, demonstrating cognitive control concurrently in behavior and the hippocampal representation of spatial information. Here we test whether rat mPFC lesion impairs the active place avoidance task to evaluate two competing hypotheses, a "central-computation" hypothesis that the mPFC is essential for the computations required for cognitive control and an alternative "local-computation" hypothesis that other brain areas can perform the computations required for cognitive control, independent of mPFC. Ibotenic acid lesion of the mPFC was effective, damaging the cingulate, prelimbic and infralimbic cortices. The lesion also altered the normal coordination of metabolic activity across remaining structures. The lesion did not impair learning to avoid the initial location of shock or long-term place avoidance memory, but impaired avoidance after the shock was relocated. The lesion also did not impair the alternation between task-relevant and task-irrelevant hippocampal representations of place information. These findings support the local-computation hypothesis that computations required for cognitive control can occur locally in brain networks independently of the mPFC.

neuroscience↗

bioRxiv2019

Socioeconomic impacts of elimination of Onchocerciasis in Abu-Hamed focus, northern Sudan: lessons after elimination

IntroductionOnchocerciasis is one of the most devastating Neglected Tropical Diseases (NTDs) and it is mostly prevalent in Africa. The disease has important heavy social and economic burdens on the infected populations including low productivity, unemployment, social isolation, and stigma. Methodology/Principal FindingsThe socio-economic impacts of the Onchocerciasis elimination in Abu-Hamed, River Nile State, Sudan; were investigated using a well-established questionnaire, 512 participants in ten affected communities were interviewed. Our findings revealed that these communities are recovering from the social and economic burden of the diseases, with 90% of the research participants reported general satisfaction about the elimination of the disease in their community, and about 48.3% of them attended secondary school or university. Only 0.6% reported unemployment, and 25.3% and 24.7% of the participants were workers and farmers respectively. Except about the vector biting and nuisance, the majority of the respondents (90%) had no complain after the elimination of the disease in the area. Also, 90.5% of the participants reported either stable or increase in their work performance during the last twelve months. About 93.8% of the respondents were engaged in normal daily activities and involved in happy events like marriage and giving birth during the last twelve months. Conclusions/SignificanceOverall, we conclude that the elimination of Onchocerciasis in Abu-Hamed has several positive impacts on the economy and social life of Abu-Hamed local communities, but this could be maximized by controlling the vector, which is still having a negative impact on the populations. Establishing local developmental projects will help these communities greatly to recover and become more productive. Author SummaryOnchocerciasis, also known as the river blindness, is a disease that caused by a parasitic worm which could infest people eyes or skin causing a blindness or sub-dermal disease. This worm is transmitted to human by the bite of an insect, the black fly. Although the disease is not fatal in most of the patient but it presents a significant economic and social burden on the infected people, their families and communities. This burden is a result of the social stigma associated with the skin form of the disease, and the lack of vision in case of blindness (ocular manifestation). Onchocerciasis was a public health problem in the study site, Abu-Hamed. In 2015, the disease was officially has been declared eliminated from the area. We investigated the socio-economic impacts of this success on the local communities. We have interviewed randomly selected 512 participants to understand their perspective and highlighting their experience regarding the disease elimination. Our research aimed to fill the gap of knowledge between the public health and social science by highlighting the social and economic benefits of health interventions and diseases elimination/eradication. Furthermore, to urge intervention programs to empower the local communities in the planning and implementation of health interventions for a better success.

microbiology↗

bioRxiv2019

A low-cost, rapidly integrated debubbler (RID) module for microfluidic cell culture applications

Microfluidic platforms use controlled fluid flow to provide physiologically relevant biochemical and biophysical cues to cultured cells in a well-defined and reproducible manner. In these systems, undisturbed flows are critical and air bubbles entering microfluidic channels can result in device delamination or cell damage. To prevent bubble entry, we report a low-cost, Rapidly Integrated Debubbler (RID) module that is simple to fabricate, inexpensive, and easily combined with existing experimental systems. We demonstrate successful removal of air bubbles spanning three orders of magnitude with a maximum removal rate (dV/dt)max = 1.5 mL min-1, at flow rates corresponding to physiological fluid-induced wall shear stresses (WSS) needed for biophysical stimulation studies on cultured mammalian cell populations.

bioengineering↗

bioRxiv2019

Interaction between DNA damage response, translation and apoptosome determines cancer susceptibility to TOP2 poisons

Topoisomerase II poisons are one of the most common class of chemotherapeutics used in cancer. We show that glioblastoma (GBM), the most malignant of all primary brain tumors in adults is responsive to TOP2 poisons. To identify genes that confer susceptibility to this drug in gliomas, we performed a genome-scale CRISPR knockout screen with etoposide. Genes involved in protein synthesis and DNA damage were implicated in etoposide susceptibility. To define potential biomarkers for TOP2 poisons, CRISPR hits were overlapped with genes whose expression correlates with susceptibility to this drug across glioma cell lines, revealing ribosomal protein subunit RPS11, 16, 18 as putative biomarkers for response to TOP2 poisons. Loss of RPS11 impaired the induction of pro-apoptotic gene APAF1 following etoposide treatment, and led to resistance to this drug and doxorubicin. The expression of these ribosomal subunits was also associated with susceptibility to TOP2 poisons across cell lines from multiple cancers.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC=\"FIGDIR/small/614024v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (14K):\norg.highwire.dtl.DTLVardef@310f7org.highwire.dtl.DTLVardef@14ed578org.highwire.dtl.DTLVardef@a0d9c0org.highwire.dtl.DTLVardef@37f59a_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2019

SVCurator: A Crowdsourcing app to visualize evidence of structural variants for the human genome

A high quality benchmark for small variants encompassing 88 to 90% of the reference genome has been developed for seven Genome in a Bottle (GIAB) reference samples. However a reliable benchmark for large indels and structural variants (SVs) is yet to be defined. In this study, we manually curated 1235 SVs which can ultimately be used to evaluate SV callers or train machine learning models. We developed a crowdsourcing app - SVCurator - to help curators manually review large indels and SVs within the human genome, and report their genotype and size accuracy.\n\nSVCurator is a Python Flask-based web platform that displays images from short, long, and linked read sequencing data from the GIAB Ashkenazi Jewish Trio son [NIST RM 8391/HG002], We asked curators to assign labels describing SV type (deletion or insertion), size accuracy, and genotype for 1235 putative insertions and deletions sampled from different size bins between 20 and 892,149 bp. The crowdsourced results were highly concordant with 37 out of the 61 curators having at least 78% concordance with a set of expert curators, where there was 93% concordance amongst expert curators. This produced high confidence labels for 935 events. When compared to the heuristic-based draft benchmark SV callset from GIAB, the SVCurator crowdsourced labels were 94.5% concordant with the benchmark set. We found that curators can successfully evaluate putative SVs when given evidence from multiple sequencing technologies.

genomics↗

bioRxiv2019

Managing genomic variant calling workflows with Swift/T

Genomic variant discovery is frequently performed using the GATK Best Practices variant calling pipeline, a complex workflow with multiple steps, fans/merges, and conditionals. This complexity makes management of the workflow difficult on a computer cluster, especially when running in parallel on large batches of data: hundreds or thousands of samples at a time. Here we describe a wrapper for the GATK-based variant calling workflow using the Swift/T parallel scripting language. Standard built-in features include the flexibility to split by chromosome before variant calling, optionally permitting the analysis to continue when faulty samples are detected, and allowing users to analyze multiple samples in parallel within each cluster node. The use of Swift/T conveys two key advantages: (1) Thanks to the embedded ability of Swift/T to transparently operate in multiple cluster scheduling environments (PBS Torque, SLURM, Cray aprun environment, etc.,) a single workflow is trivially portable across numerous clusters; (2) The leaf functions of Swift/T permit developers to easily swap executables in and out of the workflow, conditional on the analysts choice, which makes the workflow easy to maintain. This modular design permits separation of the workflow into multiple stages and the request of resources optimal for each stage of the pipeline. While Swift/Ts implicit data-level parallelism eliminates the need for the developer to code parallel analysis of multiple samples, it does make debugging of the workflow a bit more difficult, as is the case with any implicitly parallel code. With the above features, users have a powerful and portable way to scale up their variant calling analysis to run in many traditional computer cluster architectures.\n\nhttps://github.com/ncsa/Swift-T-Variant-Calling\n\nhttp://swift-t-variant-calling.readthedocs.io/en/latest/

bioinformatics↗

bioRxiv2019

CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain.

BACKGROUNDTumour cells rely on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) to survive. Thus mitochondrial OXPHOS has become an increasingly attractive area for therapeutic exploitation in cancer. However, mitochondria are required for intracellular oxygenation and normal physiological processes, and it remains unclear which mitochondrial molecular mechanisms might provide therapeutic benefit. Previously, we discovered that coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) is critical for maintaining intracellular oxygenation and required for the cellular response to hypoxia (low oxygenation) in tumour cells through molecular mechanisms that we do not yet fully understand. Overexpression of CHCHD4 in human cancers, correlates with increased tumour progression and poor patient survival.\n\nRESULTSHere, we show that elevated CHCHD4 expression provides a proliferative and metabolic advantage to tumour cells in normoxia and hypoxia. Using stable isotope labelling with amino acids in cell culture (SILAC) and analysis of the whole mitochondrial proteome, we show that CHCHD4 dynamically affects the expression of a broad range of mitochondrial respiratory chain subunits from complex I-V, including multiple subunits of complex I (CI) required for complex assembly that are essential for cell survival. We found that loss of CHCHD4 protects tumour cells from respiratory chain inhibition at CI, while elevated CHCHD4 expression in tumour cells leads to significantly increased sensitivity to CI inhibition, in part through the production of mitochondrial reactive oxygen species (ROS).\n\nCONCLUSIONSOur study highlights an important role for CHCHD4 in regulating tumour cell metabolism, and reveals that CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain and CI biology.

cell biology↗

bioRxiv2018

Robust, reproducible, and economical phosphopeptide enrichment using calcium titanate

Mass spectrometry based phosphoproteomics has revolutionized phosphoprotein analysis and enhanced our understanding of diverse and fundamental cellular processes important for human health. Because of their relative scarcity, phosphopeptides must be enriched before analysis. We demonstrate an effective and robust single-step enrichment method using an off-the-shelf preparation of calcium titanate. Our method achieves a purity and depth of analysis comparable to a widely used TiO2 based method at a reduced cost and effort.

biochemistry↗

bioRxiv2018

Generation of a versatile BiFC ORFeome library for analyzing protein-protein interactions in live Drosophila

Transcription factors achieve specificity by establishing intricate interaction networks that will change depending on the cell context. Capturing these interactions in live condition is however a challenging issue that requires sensitive and non-invasive methods. We present a set of fly lines, called \"multicolor BiFC library\", which covers most of the Drosophila transcription factors for performing Bimolecular Fluorescence Complementation (BiFC). The multicolor BiFC library can be used to probe binary or tripartite interactions and is compatible for large-scale interaction screens. The library can also be coupled with established Drosophila genetic resources to analyze interactions in the developmentally relevant expression domain of each protein partner. We provide proof of principle experiments of these various applications, using Hox proteins in the live Drosophila embryo as a case study. Overall this novel collection of ready-to-use fly lines constitutes an unprecedented genetic toolbox for the identification and analysis of protein-protein interactions in vivo.

genomics↗

bioRxiv2018

Transcriptional deconvolution reveals consistent functional subtypes of pancreatic cancer epithelium and stroma

Bulk tumor tissues comprise intermixed populations of neoplastic cells and multiple lineages of stromal cells. We used laser capture microdissection and RNA sequencing to disentangle the transcriptional programs active in the malignant epithelium and stroma of pancreatic ductal adenocarcinoma (PDA). This led to the development of a new algorithm (ADVOCATE) that accurately predicts the compartment fractions of bulk tumor samples and can computationally purify bulk gene expression data from PDA. We also present novel stromal subtypes, derived from 110 microdissected PDA stroma samples, that were enriched in extracellular matrix- and immune-associated processes. Finally, we applied ADVOCATE to systematically evaluate cross-compartment subtypes spanning four patient cohorts, revealing consistent functional classes and survival associations despite substantial compositional differences.

systems biology↗

bioRxiv2018

The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans

Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., \"direct\" inheritance). Prior studies of LTL h2 have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5,069 Bangladeshi adults with substantial relatedness. For each of the 7,254 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL (({Delta}LTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness ({phi}). The association between Tshared and ({Delta}LTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs ({phi} >0.05), the association between Tshared and ({Delta}LTL)2 (P=0.002) was stronger than the association between {phi} and ({Delta}LTL)2 (P=0.45). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere \"reprogramming\" during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direction transmission.

genetics↗