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The Journal of Experimental Biology Jan 2015Since the final decades of the last century, twin studies have made a remarkable contribution to the genetics of human complex traits and diseases. With the recent rapid... (Review)
Review
Since the final decades of the last century, twin studies have made a remarkable contribution to the genetics of human complex traits and diseases. With the recent rapid development in modern biotechnology of high-throughput genetic and genomic analyses, twin modelling is expanding from analysis of diseases to molecular phenotypes in functional genomics especially in epigenetics, a thriving field of research that concerns the environmental regulation of gene expression through DNA methylation, histone modification, microRNA and long non-coding RNA expression, etc. The application of the twin method to molecular phenotypes offers new opportunities to study the genetic (nature) and environmental (nurture) contributions to epigenetic regulation of gene activity during developmental, ageing and disease processes. Besides the classical twin model, the case co-twin design using identical twins discordant for a trait or disease is becoming a popular and powerful design for epigenome-wide association study in linking environmental exposure to differential epigenetic regulation and to disease status while controlling for individual genetic make-up. It can be expected that novel uses of twin methods in epigenetic studies are going to help with efficiently unravelling the genetic and environmental basis of epigenomics in human complex diseases.
Topics: Aging; Disease; Epigenesis, Genetic; Growth and Development; Humans; Twin Studies as Topic; Twins
PubMed: 25568460
DOI: 10.1242/jeb.107151 -
Annual Review of Pathology Jan 2017Fungi are ubiquitous in our environment, and a healthy immune system is essential to maintain adequate protection from fungal infections. When this protection breaks... (Review)
Review
Fungi are ubiquitous in our environment, and a healthy immune system is essential to maintain adequate protection from fungal infections. When this protection breaks down, superficial and invasive fungal infections cause diseases that range from irritating to life-threatening. Millions of people worldwide develop invasive infections during their lives, and mortality for these infections often exceeds 50%. Nevertheless, we are normally colonized with many of the same disease-causing fungi (e.g., on the skin or in the gut). Recent research is dramatically expanding our understanding of the mechanisms by which our immune systems interact with these organisms in health and disease. In this review, we discuss what is currently known about where and how the immune system interacts with common fungi.
Topics: Adaptive Immunity; Animals; Disease; Fungi; Humans; Immunity, Innate; Mycoses
PubMed: 28068483
DOI: 10.1146/annurev-pathol-052016-100342 -
Journal of Cellular Biochemistry Jul 2021MicroRNAs are small noncoding RNAs that can bind to the target sites in the 3'-untranslated region of messenger RNA to regulate posttranscriptional gene expression.... (Review)
Review
MicroRNAs are small noncoding RNAs that can bind to the target sites in the 3'-untranslated region of messenger RNA to regulate posttranscriptional gene expression. Increasing evidence has identified the miR-29 family, consisting of miR-29a, miR-29b-1, miR-29b-2, and miR-29c, as key regulators of a number of biological processes. Moreover, their abnormal expression contributes to the etiology of numerous diseases. In the current review, we aimed to summarize the differential expression patterns and functional roles of the miR-29 family in the etiology of diseases including osteoarthritis, osteoporosis, cardiorenal, and immune disease. Furthermore, we highlight the therapeutic potential of targeting members of miR-29 family in these diseases. We present miR-29s as promoters of osteoblast differentiation and apoptosis but suppressors of chondrogenic and osteoclast differentiation, fibrosis, and T cell differentiation, with clear avenues for therapeutic manipulation. Further research will be crucial to identify the precise mechanism of miR-29 family in these diseases and their full potential in therapeutics.
Topics: Disease; Humans; MicroRNAs
PubMed: 33529442
DOI: 10.1002/jcb.29896 -
Wiley Interdisciplinary Reviews.... Jan 2017Developmental geneticists continue to make substantial jumps in our understanding of the genetic pathways that regulate development. This understanding stems... (Review)
Review
Developmental geneticists continue to make substantial jumps in our understanding of the genetic pathways that regulate development. This understanding stems predominantly from analyses of genetically tractable model organisms developing in laboratory environments. This environment is vastly different from that in which human development occurs. As such, most causes of developmental defects in humans are thought to involve multifactorial gene-gene and gene-environment interactions. In this review, we discuss how gene-environment interactions with environmental teratogens may predispose embryos to structural malformations. We elaborate on the growing number of gene-ethanol interactions that might underlie susceptibility to fetal alcohol spectrum disorders. WIREs Dev Biol 2017, 6:e247. doi: 10.1002/wdev.247 For further resources related to this article, please visit the WIREs website.
Topics: Developmental Biology; Disease; Gene Expression Regulation, Developmental; Gene-Environment Interaction; Humans
PubMed: 27626243
DOI: 10.1002/wdev.247 -
Developmental Cell Mar 2021Each language has standard books describing that language's grammatical rules. Biologists have searched for similar, albeit more complex, principles relating enhancer... (Review)
Review
Each language has standard books describing that language's grammatical rules. Biologists have searched for similar, albeit more complex, principles relating enhancer sequence to gene expression. Here, we review the literature on enhancer grammar. We introduce dependency grammar, a model where enhancers encode information based on dependencies between enhancer features shaped by mechanistic, evolutionary, and biological constraints. Classifying enhancers based on the types of dependencies may identify unifying principles relating enhancer sequence to gene expression. Such rules would allow us to read the instructions for development within genomes and pinpoint causal enhancer variants underlying disease and evolutionary changes.
Topics: Disease; Enhancer Elements, Genetic; Evolution, Molecular; Gene Expression Regulation, Developmental; Humans
PubMed: 33689769
DOI: 10.1016/j.devcel.2021.02.016 -
Biosensors May 2018For many disease states, positive outcomes are directly linked to early diagnosis, where therapeutic intervention would be most effective. Recently, trends in disease... (Review)
Review
For many disease states, positive outcomes are directly linked to early diagnosis, where therapeutic intervention would be most effective. Recently, trends in disease diagnosis have focused on the development of label-free sensing techniques that are sensitive to low analyte concentrations found in the physiological environment. Surface-enhanced Raman spectroscopy (SERS) is a powerful vibrational spectroscopy that allows for label-free, highly sensitive, and selective detection of analytes through the amplification of localized electric fields on the surface of a plasmonic material when excited with monochromatic light. This results in enhancement of the Raman scattering signal, which allows for the detection of low concentration analytes, giving rise to the use of SERS as a diagnostic tool for disease. Here, we present a review of recent developments in the field of in vivo and in vitro SERS biosensing for a range of disease states including neurological disease, diabetes, cardiovascular disease, cancer, and viral disease.
Topics: Biosensing Techniques; Diagnostic Techniques and Procedures; Disease; Spectrum Analysis, Raman
PubMed: 29751641
DOI: 10.3390/bios8020046 -
International Journal of Molecular... Jun 2021Mitochondrial dysfunction is known to contribute to mitochondrial diseases, as well as to a variety of aging-based pathologies. Mitochondria have their own genomes... (Review)
Review
Mitochondrial dysfunction is known to contribute to mitochondrial diseases, as well as to a variety of aging-based pathologies. Mitochondria have their own genomes (mitochondrial DNA (mtDNA)) and the abnormalities, such as point mutations, deletions, and copy number variations, are involved in mitochondrial dysfunction. In recent years, several epidemiological studies and animal experiments have supported the Developmental Origin of Health and Disease (DOHaD) theory, which states that the environment during fetal life influences the predisposition to disease and the risk of morbidity in adulthood. Mitochondria play a central role in energy production, as well as in various cellular functions, such as apoptosis, lipid metabolism, and calcium metabolism. In terms of the DOHaD theory, mtDNA copy number may be a mediator of health and disease. This paper summarizes the results of recent epidemiological studies on the relationship between environmental factors and mtDNA copy number during pregnancy from the perspective of DOHaD theory. The results of these studies suggest a hypothesis that mtDNA copy number may reflect environmental influences during fetal life and possibly serve as a surrogate marker of health risks in adulthood.
Topics: Animals; DNA Copy Number Variations; DNA, Mitochondrial; Disease; Female; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 34205712
DOI: 10.3390/ijms22126634 -
Science (New York, N.Y.) Sep 2021The sequencing of the human genome has allowed the study of the genetic architecture of common diseases: the number of genomic variants that contribute to risk of... (Review)
Review
The sequencing of the human genome has allowed the study of the genetic architecture of common diseases: the number of genomic variants that contribute to risk of disease and their joint frequency and effect size distribution. Common diseases are polygenic, with many loci contributing to phenotype, and the cumulative burden of risk alleles determines individual risk in conjunction with environmental factors. Most risk loci occur in noncoding regions of the genome regulating cell- and context-specific gene expression. Although the effect sizes of most risk alleles are small, their cumulative effects in individuals, quantified as a polygenic (risk) score, can identify people at increased risk of disease, thereby facilitating prevention or early intervention.
Topics: Disease; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Models, Genetic; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Rare Diseases; Selection, Genetic; Whole Genome Sequencing
PubMed: 34554790
DOI: 10.1126/science.abi8206 -
Journal of Molecular Biology Oct 2017Aberrant R-loop structures are increasingly being realized as an important contributor to human disease. R loops, which are mainly co-transcriptional, abundant RNA/DNA... (Review)
Review
Aberrant R-loop structures are increasingly being realized as an important contributor to human disease. R loops, which are mainly co-transcriptional, abundant RNA/DNA hybrids, form naturally and can indeed be beneficial for transcription regulation at certain loci. However, their unwanted persistence elsewhere or in particular situations can lead to DNA double-strand breaks, chromosome rearrangements, and hypermutation, which are all sources of genomic instability. Mutations in genes involved in R-loop resolution or mutations leading to R-loop formation at specific genes affect the normal physiology of the cell. We discuss here the examples of diseases for which a link with R loops has been described, as well as how disease-causing mutations might participate in the development and/or progression of diseases that include repeat-associated conditions, other neurological disorders, and cancers.
Topics: DNA Replication; Disease; Gene Expression Regulation; Genomic Instability; Humans; Nucleic Acid Conformation; Transcription, Genetic
PubMed: 27600412
DOI: 10.1016/j.jmb.2016.08.031 -
Cold Spring Harbor Perspectives in... May 2021Major biotechnological advances have facilitated a tremendous boost to the collection of (gen-/transcript-/prote-/methyl-/metabol-)omics data in very large sample sizes... (Review)
Review
Major biotechnological advances have facilitated a tremendous boost to the collection of (gen-/transcript-/prote-/methyl-/metabol-)omics data in very large sample sizes worldwide. Coordinated efforts have yielded a deluge of studies associating diseases with genetic markers (genome-wide association studies) or with molecular phenotypes. Whereas omics-disease associations have led to biologically meaningful and coherent mechanisms, the identified (non-germline) disease biomarkers may simply be correlates or consequences of the explored diseases. To move beyond this realm, Mendelian randomization provides a principled framework to integrate information on omics- and disease-associated genetic variants to pinpoint molecular traits causally driving disease development. In this review, we show the latest advances in this field, flag up key challenges for the future, and propose potential solutions.
Topics: Biomarkers; Biotechnology; Disease; Genome-Wide Association Study; Humans; Multifactorial Inheritance; Phenotype
PubMed: 32816877
DOI: 10.1101/cshperspect.a040493