scholarly journals The Genetic Variability of APOE in Different Human Populations and Its Implications for Longevity

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 222 ◽  
Author(s):  
Paolo Abondio ◽  
Marco Sazzini ◽  
Paolo Garagnani ◽  
Alessio Boattini ◽  
Daniela Monti ◽  
...  
Keyword(s):  
Evolutionary Dynamics ◽  
Human Longevity ◽  
Human Populations ◽  
Worldwide Distribution ◽  
Age Related ◽  
Gene Environment ◽  
Genome Wide ◽  
History Of ◽  
Extreme Longevity ◽  
Adaptive Role

Human longevity is a complex phenotype resulting from the combinations of context-dependent gene-environment interactions that require analysis as a dynamic process in a cohesive ecological and evolutionary framework. Genome-wide association (GWAS) and whole-genome sequencing (WGS) studies on centenarians pointed toward the inclusion of the apolipoprotein E (APOE) polymorphisms ε2 and ε4, as implicated in the attainment of extreme longevity, which refers to their effect in age-related Alzheimer’s disease (AD) and cardiovascular disease (CVD). In this case, the available literature on APOE and its involvement in longevity is described according to an anthropological and population genetics perspective. This aims to highlight the evolutionary history of this gene, how its participation in several biological pathways relates to human longevity, and which evolutionary dynamics may have shaped the distribution of APOE haplotypes across the globe. Its potential adaptive role will be described along with implications for the study of longevity in different human groups. This review also presents an updated overview of the worldwide distribution of APOE alleles based on modern day data from public databases and ancient DNA samples retrieved from literature in the attempt to understand the spatial and temporal frame in which present-day patterns of APOE variation evolved.

scholarly journals Comparative Analysis of Chlamydia psittaci Genomes Reveals the Recent Emergence of a Pathogenic Lineage with a Broad Host Range

mBio ◽  
2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Timothy D. Read ◽  
Sandeep J. Joseph ◽  
Xavier Didelot ◽  
Brooke Liang ◽  
Lisa Patel ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
New World ◽  
Evolutionary Dynamics ◽  
Chlamydia Psittaci ◽  
South American ◽  
Content Type ◽  
Sexually Transmitted ◽  
Genome Wide ◽  
Life Threatening ◽  
History Of

ABSTRACT Chlamydia psittaci is an obligate intracellular bacterium. Interest in Chlamydia stems from its high degree of virulence as an intestinal and pulmonary pathogen across a broad range of animals, including humans. C. psittaci human pulmonary infections, referred to as psittacosis, can be life-threatening, which is why the organism was developed as a bioweapon in the 20th century and is listed as a CDC biothreat agent. One remarkable recent result from comparative genomics is the finding of frequent homologous recombination across the genome of the sexually transmitted and trachoma pathogen Chlamydia trachomatis. We sought to determine if similar evolutionary dynamics occurred in C. psittaci. We analyzed 20 C. psittaci genomes from diverse strains representing the nine known serotypes of the organism as well as infections in a range of birds and mammals, including humans. Genome annotation revealed a core genome in all strains of 911 genes. Our analyses showed that C. psittaci has a history of frequently switching hosts and undergoing recombination more often than C. trachomatis. Evolutionary history reconstructions showed genome-wide homologous recombination and evidence of whole-plasmid exchange. Tracking the origins of recombinant segments revealed that some strains have imported DNA from as-yet-unsampled or -unsequenced C. psittaci lineages or other Chlamydiaceae species. Three ancestral populations of C. psittaci were predicted, explaining the current population structure. Molecular clock analysis found that certain strains are part of a clonal epidemic expansion likely introduced into North America by South American bird traders, suggesting that psittacosis is a recently emerged disease originating in New World parrots. IMPORTANCE Chlamydia psittaci is classified as a CDC biothreat agent based on its association with life-threatening lung disease, termed psittacosis, in humans. Because of the recent remarkable findings of frequent recombination across the genome of the human sexually transmitted and ocular trachoma pathogen Chlamydia trachomatis, we sought to determine if similar evolutionary dynamics occur in C. psittaci. Twenty C. psittaci genomes were analyzed from diverse strains that may play a pathogenic role in human disease. Evolution of the strains revealed genome-wide recombination occurring at a higher rate than for C. trachomatis. Certain strains were discovered to be part of a recent epidemic clonal expansion originating in South America. These strains may have been introduced into the United States from South American bird traders, suggesting that psittacosis is a recently emerged disease originating in New World parrots. Our analyses indicate that C. psittaci strains have a history of frequently switching hosts and undergoing recombination.

scholarly journals A Genome-Wide Scan Reveals Important Roles of DNA Methylation in Human Longevity by Regulating Age-Related Disease Genes

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120388 ◽  
Author(s):  
Fu-Hui Xiao ◽  
Yong-Han He ◽  
Qi-Gang Li ◽  
Huan Wu ◽  
Long-Hai Luo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Longevity ◽  
Disease Genes ◽  
Related Disease ◽  
Age Related ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Scan

scholarly journals Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity

PLoS Genetics ◽  
2015 ◽  
Vol 11 (12) ◽  
pp. e1005728 ◽  
Author(s):  
Kristen Fortney ◽  
Edgar Dobriban ◽  
Paolo Garagnani ◽  
Chiara Pirazzini ◽  
Daniela Monti ◽  
...  
Keyword(s):  
Human Longevity ◽  
Related Disease ◽  
Age Related ◽  
Genome Wide ◽  
Genome Wide Scan

scholarly journals Footprints in the Sand: Deep Taxonomic Comparisons in Vertebrate Genomics to Unveil the Genetic Programs of Human Longevity

2021 ◽  
Vol 12 ◽  
Author(s):  
Stephen Treaster ◽  
David Karasik ◽  
Matthew P. Harris
Keyword(s):  
Meta Analysis ◽  
Population Level ◽  
Human Longevity ◽  
Comparative Genomic ◽  
Human Populations ◽  
Key Factors ◽  
Genetic Constraints ◽  
Genomic Signatures ◽  
Human Lifespan ◽  
Age Related

With the modern quality, quantity, and availability of genomic sequencing across species, as well as across the expanse of human populations, we can screen for shared signatures underlying longevity and lifespan. Knowledge of these mechanisms would be medically invaluable in combating aging and age-related diseases. The diversity of longevities across vertebrates is an opportunity to look for patterns of genetic variation that may signal how this life history property is regulated, and ultimately how it can be modulated. Variation in human longevity provides a unique window to look for cases of extreme lifespan within a population, as well as associations across populations for factors that influence capacity to live longer. Current large cohort studies support the use of population level analyses to identify key factors associating with human lifespan. These studies are powerful in concept, but have demonstrated limited ability to resolve signals from background variation. In parallel, the expanding catalog of sequencing and annotation from diverse species, some of which have evolved longevities well past a human lifespan, provides independent cases to look at the genomic signatures of longevity. Recent comparative genomic work has shown promise in finding shared mechanisms associating with longevity among distantly related vertebrate groups. Given the genetic constraints between vertebrates, we posit that a combination of approaches, of parallel meta-analysis of human longevity along with refined analysis of other vertebrate clades having exceptional longevity, will aid in resolving key regulators of enhanced lifespan that have proven to be elusive when analyzed in isolation.

scholarly journals A joint analysis of longevity and age-related disease variants for gene expression association

2021 ◽  
Author(s):  
Lu Zeng ◽  
Shouneng Peng ◽  
Seungsoo Kim ◽  
Jun Zhu ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variants ◽  
Gene Expression Regulation ◽  
Human Longevity ◽  
Joint Analysis ◽  
Putative Gene ◽  
Related Disease ◽  
Age Related ◽  
Genome Wide

AbstractA large number of genetic variants associated with human longevity have been reported but how they play their functions remains elusive. We performed an integrative analysis on 113 genome-wide significant longevity and 14,529 age-related disease variants in the context of putative gene expression regulation. We found that most of the longevity allele types were different from the genotype of disease alleles when they were localized at the same chromosomal positions. Longevity variants were about eight times more likely to be associated with gene expression than randomly selected variants. The directions of the gene expression association were more likely to be opposite between longevity and disease variants when the association occurred to the same gene. Many longevity variants likely function through down-regulating inflammatory response and up-regulating healthy lipid metabolisms. In conclusion, this work helps to elucidate the potential mechanisms of longevity variants for follow-up studies to discover methods to extend human healthspan.

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