scholarly journals WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lilit Nersisyan ◽  
◽  
Maria Nikoghosyan ◽  
Arsen Arakelyan
Keyword(s):  
Telomere Length ◽  
Telomere Maintenance ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Association Analyses ◽  
Relative Contribution ◽  
Age Related ◽  
Small Influence ◽  
Ribonuclease Reductase ◽  
Length Analysis

AbstractTelomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated, however, their relative contribution to TL variability is still understudied. We have used whole genome sequencing data of 250 family trios from the Genome of the Netherlands project to perform computational measurement of TL and a series of regression and genome-wide association analyses to reveal TL inheritance patterns and associated genetic factors. Our results confirm that TL is a largely heritable trait, primarily with mother’s, and, to a lesser extent, with father’s TL having the strongest influence on the offspring. In this cohort, mother’s, but not father’s age at conception was positively linked to offspring TL. Age-related TL attrition of 40 bp/year had relatively small influence on TL variability. Finally, we have identified TL-associated variations in ribonuclease reductase catalytic subunit M1 (RRM1 gene), which is known to regulate telomere maintenance in yeast. We also highlight the importance of multivariate approach and the limitations of existing tools for the analysis of TL as a polygenic heritable quantitative trait.

scholarly journals The age of heterozygous telomerase mutant parents influences the adult phenotype of their offspring irrespective of genotype in zebrafish

2017 ◽  
Vol 2 ◽  
pp. 77
Author(s):  
Catherine M. Scahill ◽  
Zsofia Digby ◽  
Ian M. Sealy ◽  
Richard J. White ◽  
John E. Collins ◽  
...  
Keyword(s):  
Telomere Length ◽  
Dyskeratosis Congenita ◽  
Telomere Maintenance ◽  
Sex Bias ◽  
Whole Genome Sequencing Data ◽  
Dependent Manner ◽  
Sequencing Data ◽  
Older Parents ◽  
Male Sex ◽  
Length Analysis

Background: Mutations in proteins involved in telomere maintenance lead to a range of human diseases, including dyskeratosis congenita, idiopathic pulmonary fibrosis and cancer. Telomerase functions to add telomeric repeats back onto the ends of chromosomes, however non-canonical roles of components of telomerase have recently been suggested. Methods: Here we use a zebrafish telomerase mutant which harbours a nonsense mutation in tert to investigate the adult phenotypes of fish derived from heterozygous parents of different ages. Furthermore we use whole genome sequencing data to estimate average telomere lengths. Results: We show that homozygous offspring from older heterozygotes exhibit signs of body wasting at a younger age than those of younger parents, and that offspring of older heterozygous parents weigh less irrespective of genotype. We also demonstrate that tert homozygous mutant fish have a male sex bias, and that clutches from older parents also have a male sex bias in the heterozygous and wild-type populations. Telomere length analysis reveals that the telomeres of younger heterozygous parents are shorter than those of older heterozygous parents. Conclusions: These data indicate that the phenotypes observed in offspring from older parents cannot be explained by telomere length. Instead we propose that Tert functions outside of telomere length maintenance in an age-dependent manner to influence the adult phenotypes of the next generation.

scholarly journals The age of heterozygous telomerase mutant parents influences the adult phenotype of their offspring irrespective of genotype in zebrafish

2018 ◽  
Vol 2 ◽  
pp. 77
Author(s):  
Catherine M. Scahill ◽  
Zsofia Digby ◽  
Ian M. Sealy ◽  
Richard J. White ◽  
Neha Wali ◽  
...  
Keyword(s):  
Telomere Length ◽  
Dyskeratosis Congenita ◽  
Telomere Maintenance ◽  
Sex Bias ◽  
Whole Genome Sequencing Data ◽  
Dependent Manner ◽  
Sequencing Data ◽  
Older Parents ◽  
Male Sex ◽  
Length Analysis

Background: Mutations in proteins involved in telomere maintenance lead to a range of human diseases, including dyskeratosis congenita, idiopathic pulmonary fibrosis and cancer. Telomerase functions to add telomeric repeats back onto the ends of chromosomes, however non-canonical roles of components of telomerase have recently been suggested. Methods: Here we use a zebrafish telomerase mutant which harbours a nonsense mutation in tert to investigate the adult phenotypes of fish derived from heterozygous parents of different ages. Furthermore we use whole genome sequencing data to estimate average telomere lengths. Results: We show that homozygous offspring from older heterozygotes exhibit signs of body wasting at a younger age than those of younger parents, and that offspring of older heterozygous parents weigh less irrespective of genotype. We also demonstrate that tert homozygous mutant fish have a male sex bias, and that clutches from older parents also have a male sex bias in the heterozygous and wild-type populations. Telomere length analysis reveals that the telomeres of younger heterozygous parents are shorter than those of older heterozygous parents. Conclusions: These data indicate that the phenotypes observed in offspring from older parents cannot be explained by telomere length. Instead we propose that Tert functions outside of telomere length maintenance in an age-dependent manner to influence the adult phenotypes of the next generation.

scholarly journals Telomere length and TERT expression are associated with age in almond (Prunus dulcis [Mill.] D.A.Webb)

2020 ◽  
Author(s):  
Katherine M. D’Amico-Willman ◽  
Elizabeth Anderson ◽  
Thomas M. Gradziel ◽  
Jonathan Fresnedo-Ramírez
Keyword(s):  
Telomere Length ◽  
Prunus Dulcis ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Perennial Crop ◽  
Related Disorder ◽  
Age Cohorts ◽  
Perennial Plant ◽  
Biomarkers Of Aging ◽  
Age Related

AbstractWhile it is well known that all organisms age, our understanding of how aging occurs varies dramatically among species. The aging process in perennial plants is not well defined, yet can have implications on production and yield of valuable fruit and nut crops. Almond, a relevant nut crop, exhibits an age-related disorder known as non-infectious bud failure (BF) that affects vegetative bud development, indirectly affecting kernel-yield. This species and disorder present an opportunity to address aging in a commercially-relevant and vegetatively-propagated, perennial crop threatened by an aging-related disorder. In this study, we tested the hypothesis that telomere length and/or TERT expression can serve as biomarkers of aging in almond using both whole-genome sequencing data and leaf samples collected from distinct age cohorts over a two-year period. To measure telomere lengths, we employed both in silico and molecular approaches. We also measured expression of TERT, a subunit of the enzyme telomerase, which is responsible for maintaining telomere lengths. Results from this work show a marginal but significant association between both telomere length measured by monochrome multiplex quantitative PCR and TERT expression, and age of almond seedlings. These results suggest that as almonds age, TERT expression decreases and telomeres shorten. This work provides valuable information on potential biomarkers of perennial plant aging, contributing to our limited knowledge of this process. In addition, translation of this information will provide opportunities to address BF in almond breeding and nursery propagation.

scholarly journals Telomere length and human hippocampal neurogenesis

2020 ◽  
Vol 45 (13) ◽  
pp. 2239-2247 ◽  
Author(s):  
Alish B. Palmos ◽  
Rodrigo R. R. Duarte ◽  
Demelza M. Smeeth ◽  
Erin C. Hedges ◽  
Douglas F. Nixon ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Psychiatric Disorder ◽  
Telomere Length ◽  
Gene Networks ◽  
Hippocampal Neurogenesis ◽  
Telomere Maintenance ◽  
Adult Hippocampal Neurogenesis ◽  
Telomere Shortening ◽  
Age Related

Abstract Short telomere length is a risk factor for age-related disease, but it is also associated with reduced hippocampal volumes, age-related cognitive decline and psychiatric disorder risk. The current study explored whether telomere shortening might have an influence on cognitive function and psychiatric disorder pathophysiology, via its hypothesised effects on adult hippocampal neurogenesis. We modelled telomere shortening in human hippocampal progenitor cells in vitro using a serial passaging protocol that mimics the end-replication problem. Serially passaged progenitors demonstrated shorter telomeres (P ≤ 0.05), and reduced rates of cell proliferation (P ≤ 0.001), with no changes in the ability of cells to differentiate into neurons or glia. RNA-sequencing and gene-set enrichment analyses revealed an effect of cell ageing on gene networks related to neurogenesis, telomere maintenance, cell senescence and cytokine production. Downregulated transcripts in our model showed a significant overlap with genes regulating cognitive function (P ≤ 1 × 10−5), and risk for schizophrenia (P ≤ 1 × 10−10) and bipolar disorder (P ≤ 0.005). Collectively, our results suggest that telomere shortening could represent a mechanism that moderates the proliferative capacity of human hippocampal progenitors, which may subsequently impact on human cognitive function and psychiatric disorder pathophysiology.

scholarly journals The effects of development and chronic oxidative stress on telomere length in an agricultural pest moth, Helicoverpa armigera

2020 ◽  
Author(s):  
Nonthakorn (Beatrice) Apirajkamol ◽  
Tom K Walsh ◽  
Angela McGaughran
Keyword(s):  
Oxidative Stress ◽  
Telomere Length ◽  
Helicoverpa Armigera ◽  
Developmental Stages ◽  
Repetitive Sequences ◽  
Telomere Maintenance ◽  
Cell Replication ◽  
Sequencing Data ◽  
Replication Process ◽  
Helicoverpa Armígera

Telomeres are repetitive sequences located at the end of chromosomes in eukaryotes that protect against loss of important sequences during the cell replication process. Telomere length (TL) shortens with every round of cell division. When a telomere becomes too short, cells can no longer proliferate and this triggers the cell apoptosis process. Apart from cell replication, the length of telomeres can be affected by factors such as sex, genetics, and stress levels. Oxidative stress in particular can cause damage to telomeres and telomere maintenance processes, resulting in TL shortening. This phenomenon occurs in humans and many vertebrates, especially endothermic species. However, the ways in which various stress types affect the TL of invertebrate species remains ambiguous. Here, we examined the effects of development and oxidative stress on TL in the invertebrate pest moth, Helicoverpa armigera . In the former case, we extracted genomic DNA from three developmental stages (1-day old egg, 4th instar, and first-day emerged moths) and measured TL by qPCR . In the latter, we chronically expos ed individuals to paraquat – an organic herbicide that induces oxidative stress - and then measured TL as per our development methodology . In addition, we examined TL in a subset of published whole genome short-read sequencing data of caterpillars and moths using the software, Computel. In our experimental work, we found that TL in H. armigera was significantly longer at the early stages of development and shortens in later stages. However, oxidative stress does not appear to shorten TL in H. armigera following chronic exposure to paraquat. In our Computel analysis, we found that caterpillars had longer mean TL than moths but this difference was not significant due to the high variation among samples. Collectively, our research provides new data on TL in an underrepresented group, adding new insights into the progression of TL shortening with development and the effects of oxidative stress on TL, while also more generally highlighting the value of applying complementary approaches to TL measurement.

scholarly journals Characterization of the Leaf Microbiome from Whole-Genome Sequencing Data of the 3000 Rice Genomes Project

Rice ◽  
2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Veronica Roman-Reyna ◽  
Dale Pinili ◽  
Frances N. Borja ◽  
Ian L. Quibod ◽  
Simon C. Groen ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Crop Improvement ◽  
Rice Genome ◽  
Plant Genome ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Rice Leaf ◽  
Relative Contribution ◽  
Bacterial Microbiome ◽  
Host Microbe Interactions

Abstract Background The crop microbial communities are shaped by interactions between the host, microbes and the environment, however, their relative contribution is beginning to be understood. Here, we explore these interactions in the leaf bacterial community across 3024 rice accessions. Findings By using unmapped DNA sequencing reads as microbial reads, we characterized the structure of the rice bacterial microbiome. We identified central bacteria taxa that emerge as microbial “hubs” and may have an influence on the network of host-microbe interactions. We found regions in the rice genome that might control the assembly of these microbial hubs. To our knowledge this is one of the first studies that uses raw data from plant genome sequencing projects to characterize the leaf bacterial communities. Conclusion We showed, that the structure of the rice leaf microbiome is modulated by multiple interactions among host, microbes, and environment. Our data provide insight into the factors influencing microbial assemblage in the rice leaf and also opens the door for future initiatives to modulate rice consortia for crop improvement efforts.

scholarly journals Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data

2017 ◽  
Author(s):  
James HR Farmery ◽  
Mike L Smith ◽  
Andy G Lynch ◽  
Keyword(s):  
Whole Genome Sequencing ◽  
Telomere Length ◽  
Genome Sequencing ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Cancer Data ◽  
Sequencing Errors ◽  
Novel Approach ◽  
Telomere Biology

ABSTRACTTelomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, technical replicates, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype.

scholarly journals Characterization of the leaf microbiome from whole-genome sequencing data of the 3000 rice genomes project.

2020 ◽  
Author(s):  
Veronica Roman-Reyna ◽  
Dale Pinili ◽  
Frances Nikki Borja ◽  
Ian Lorenzo Quibod ◽  
Simon C. Groen ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Crop Improvement ◽  
Rice Genome ◽  
Plant Genome ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Rice Leaf ◽  
Relative Contribution ◽  
Bacterial Microbiome ◽  
Host Microbe Interactions

Abstract Background: The crop microbial communities are shaped by interactions between the host, microbes and the environment, however, their relative contribution is beginning to be understood. Here, we explore these interactions in the leaf bacterial community across 3,024 rice accessions. Findings: By using unmapped DNA sequencing reads as microbial reads, we characterized the structure of the rice bacterial microbiome. We identified central bacteria taxa that emerge as microbial “hubs” and may have an influence on the network of host-microbe interactions. We found regions in the rice genome that might control the assembly of these microbial hubs. To our knowledge this is one of the first studies that uses raw data from plant genome sequencing projects to characterize the leaf bacterial communities. Conclusion: We showed, that the structure of the rice leaf microbiome is modulated by multiple interactions among host, microbes, and environment. Our data provide insight into the factors influencing microbial assemblage in the rice leaf and also opens the door for future initiatives to modulate rice consortia for crop improvement efforts.

scholarly journals Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity

2011 ◽  
Vol 13 (2) ◽  
pp. 119-131 ◽  
Author(s):  
Sangkyu Kim ◽  
Xiuhua Bi ◽  
Malwina Czarny-Ratajczak ◽  
Jianliang Dai ◽  
David A. Welsh ◽  
...  
Keyword(s):  
Telomere Length ◽  
Telomere Maintenance ◽  
Human Longevity ◽  
Age Related
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