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Biochemical Society Transactions Aug 2016Many human diseases have been attributed to mutation in the protein coding regions of the human genome. The protein coding portion of the human genome, however, is very... (Review)
Review
Many human diseases have been attributed to mutation in the protein coding regions of the human genome. The protein coding portion of the human genome, however, is very small compared with the non-coding portion of the genome. As such, there are a disproportionate number of diseases attributed to the coding compared with the non-coding portion of the genome. It is now clear that the non-coding portion of the genome produces many functional non-coding RNAs and these RNAs are slowly being linked to human diseases. Here we discuss examples where mutation in classical non-coding RNAs have been attributed to human disease and identify the future potential for the non-coding portion of the genome in disease biology.
Topics: Disease; Gene Expression; Genetic Predisposition to Disease; Genome, Human; Humans; Models, Genetic; Mutation; RNA; RNA, Mitochondrial; RNA, Untranslated
PubMed: 27528754
DOI: 10.1042/BST20160089 -
American Journal of Medical Genetics.... Nov 2021The Human Genome Organization (HUGO) was initially established in 1988 to help integrate international scientific genomic activity and to accelerate the diffusion of...
The Human Genome Organization (HUGO) was initially established in 1988 to help integrate international scientific genomic activity and to accelerate the diffusion of knowledge from the efforts of the human genome project. Its founding President was Victor McKusick. During the late 1980s and 1990s, HUGO organized lively gene mapping meetings to accurately place genes on the genome as chromosomes were being sequenced. With the completion of the Human Genome Project, HUGO went through some transitions and self-reflection. In 2020, HUGO (which hosts a large annual scientific meeting and comprises the renowned HUGO Gene Nomenclature Committee [HGNC], responsible for naming genes, and an outstanding Ethics Committee) was merged with the Human Genome Variation Society (HGVS; which defines the correct nomenclature for variation description) and the Human Variome Project (HVP; championed by the late Richard Cotton) into a single organization that is committed to assembling human genomic variation from all over the world. This consolidated effort, under a new Executive Board and seven focused committees, will facilitate efficient and effective communication and action to bring the benefits of increasing knowledge of genome diversity and biology to people all over the world.
Topics: Databases, Genetic; Genetic Variation; Genome, Human; Genomics; History, 20th Century; Human Genetics; Human Genome Project; Humans
PubMed: 34581472
DOI: 10.1002/ajmg.a.62512 -
Biology of Blood and Marrow... Jan 2011Crick, Watson, and colleagues revealed the genetic code in 1953, and since that time, remarkable progress has been made in understanding what makes each of us who we... (Review)
Review
Crick, Watson, and colleagues revealed the genetic code in 1953, and since that time, remarkable progress has been made in understanding what makes each of us who we are. Identification of single genes important in disease, and the development of a mechanistic understanding of genetic elements that regulate gene function, have cast light on the pathophysiology of many heritable and acquired disorders. In 1990, the human genome project commenced, with the goal of sequencing the entire human genome, and a "first draft" was published with astonishing speed in 2001. The first draft, although an extraordinary achievement, reported essentially an imaginary haploid mix of alleles rather than a true diploid genome. In the years since 2001, technology has further improved, and efforts have been focused on filling in the gaps in the initial genome and starting the huge task of looking at normal variation in the human genome. This work is the beginning of understanding human genetics in the context of the structure of the genome as a complete entity, and as more than simply the sum of a series of genes. We present 3 studies in this review that apply genomic approaches to leukemia and to transplantation to improve and extend therapies.
Topics: Genome, Human; Genomics; Hematopoietic Stem Cell Transplantation; Humans; Leukemia
PubMed: 21195310
DOI: 10.1016/j.bbmt.2010.10.026 -
Current Opinion in Genetics &... Dec 2016High altitude, defined as elevations lying above 2500m sea level, challenges human survival and reproduction. This environment provides a natural experimental design... (Review)
Review
High altitude, defined as elevations lying above 2500m sea level, challenges human survival and reproduction. This environment provides a natural experimental design wherein specific populations, Andeans, Ethiopians, and Tibetans, have lived in a chronic hypoxia state for millennia. These human groups have overcome the low ambient oxygen tension of high elevation via unique physiologic and genetic adaptations. Genomic studies have identified several genes that underlie high-altitude adaptive phenotypes, many of which are central components of the Hypoxia Inducible Factor (HIF) pathway. Further study of mechanisms governing the adaptive changes responsible for high-altitude adaptation will contribute to our understanding of the molecular basis of evolutionary change and assist in the functional annotation of the human genome.
Topics: Adaptation, Physiological; Altitude; Genome, Human; Genomics; Humans; Hypoxia; Phenotype; Polymorphism, Single Nucleotide; Selection, Genetic
PubMed: 27501156
DOI: 10.1016/j.gde.2016.06.018 -
The Journal of Pathology Jul 2021Human genetics plays an increasingly important role in drug development and population health. Here we review the history of human genetics in the context of... (Review)
Review
Human genetics plays an increasingly important role in drug development and population health. Here we review the history of human genetics in the context of accelerating the discovery of therapies, present examples of how human genetics evidence supports successful drug targets, and discuss how polygenic risk scores could be beneficial in various clinical settings. We highlight the value of direct-to-consumer platforms in the era of fast-paced big data biotechnology, and how diverse genetic and health data can benefit society. © 2021 23andMe, Inc. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Drug Discovery; Genome, Human; Humans
PubMed: 33748968
DOI: 10.1002/path.5664 -
Nature Reviews. Genetics Jun 2014Discoveries over the past decade portend a paradigm shift in molecular biology. Evidence suggests that RNA is not only functional as a messenger between DNA and protein... (Review)
Review
Discoveries over the past decade portend a paradigm shift in molecular biology. Evidence suggests that RNA is not only functional as a messenger between DNA and protein but also involved in the regulation of genome organization and gene expression, which is increasingly elaborate in complex organisms. Regulatory RNA seems to operate at many levels; in particular, it plays an important part in the epigenetic processes that control differentiation and development. These discoveries suggest a central role for RNA in human evolution and ontogeny. Here, we review the emergence of the previously unsuspected world of regulatory RNA from a historical perspective.
Topics: Animals; Epigenesis, Genetic; Evolution, Molecular; Genome, Human; Humans; RNA, Untranslated
PubMed: 24776770
DOI: 10.1038/nrg3722 -
Communications Biology Sep 2023Repetitive DNA sequences playing critical roles in driving evolution, inducing variation, and regulating gene expression. In this review, we summarized the definition,... (Review)
Review
Repetitive DNA sequences playing critical roles in driving evolution, inducing variation, and regulating gene expression. In this review, we summarized the definition, arrangement, and structural characteristics of repeats. Besides, we introduced diverse biological functions of repeats and reviewed existing methods for automatic repeat detection, classification, and masking. Finally, we analyzed the type, structure, and regulation of repeats in the human genome and their role in the induction of complex diseases. We believe that this review will facilitate a comprehensive understanding of repeats and provide guidance for repeat annotation and in-depth exploration of its association with human diseases.
Topics: Humans; Genome, Human; Base Sequence
PubMed: 37726397
DOI: 10.1038/s42003-023-05322-y -
BMC Research Notes Feb 2019Basic parameters commonly used to describe genomes including length, weight and relative guanine-cytosine (GC) content are widely cited in absence of a primary source....
OBJECTIVE
Basic parameters commonly used to describe genomes including length, weight and relative guanine-cytosine (GC) content are widely cited in absence of a primary source. By using updated data and original software we determined these values to the best of our knowledge as standard reference for the whole human nuclear genome, for each chromosome and for mitochondrial DNA. We also devised a method to calculate the relative GC content in the whole messenger RNA sequence set and in transcriptomes by multiplying the GC content of each gene by its mean expression level.
RESULTS
The male nuclear diploid genome extends for 6.27 Gigabase pairs (Gbp), is 205.00 cm (cm) long and weighs 6.41 picograms (pg). Female values are 6.37 Gbp, 208.23 cm, 6.51 pg. The individual variability and the implication for the DNA informational density in terms of bits/volume were discussed. The genomic GC content is 40.9%. Following analysis in different transcriptomes and species, we showed that the greatest deviation was observed in the pathological condition analysed (trisomy 21 leukaemic cells) and in Caenorhabditis elegans. Our results may represent a solid basis for further investigation on human structural and functional genomics while also providing a framework for other genome comparative analysis.
Topics: Base Composition; DNA, Mitochondrial; Female; Genome, Human; Genomics; Humans; Male
PubMed: 30813969
DOI: 10.1186/s13104-019-4137-z -
International Journal of Environmental... May 2022To date, the controversy surrounding the unknown risks and consequences of heritable genome editing has grown, with such work raising biosafety and ethical concerns for...
To date, the controversy surrounding the unknown risks and consequences of heritable genome editing has grown, with such work raising biosafety and ethical concerns for future generations. However, the current guideline of global governance is limited. In the context of the new framework for the governance of human genome editing developed by the World Health Organization (WHO) committee, this paper presents further analysis by highlighting predicaments of governance on germline engineering that merit the most attention: (1) building a scientific culture informed by a broader set of values and considerations in the internal scientific community at large, such as codes of ethics, and education, in addition to awareness-raising measures; and (2) reflecting on and institutionalizing policies in grassroots practice according to local conditions in external governance, such as the experimentalist governance, which is a multi-layered model of governance that establishes an open-ended framework from the top and offers stakeholders the freedom of discussion. The key to achieving these goals is more democratic deliberation between the public and the inclusive engagement of the global scientific community, which has been extensively used in the Biological and Toxin Weapons Convention (BTWC). On a global scale, we believe that practicing heritable human genome editing in accordance with the WHO and BTWC appears to be a good choice.
Topics: Gene Editing; Genome, Human; Germ Cells; Humans; Morals
PubMed: 35682323
DOI: 10.3390/ijerph19116739 -
Human Molecular Genetics Oct 2022Every cell in the human body inherits a copy of the same genetic information. The three billion base pairs of DNA in the human genome, and the roughly 50 000 coding...
Every cell in the human body inherits a copy of the same genetic information. The three billion base pairs of DNA in the human genome, and the roughly 50 000 coding and non-coding genes they contain, must thus encode all the complexity of human development and cell and tissue type diversity. Differences in gene regulation, or the modulation of gene expression, enable individual cells to interpret the genome differently to carry out their specific functions. Here we discuss recent and ongoing efforts to build gene regulatory maps, which aim to characterize the regulatory roles of all sequences in a genome. Many researchers and consortia have identified such regulatory elements using functional assays and evolutionary analyses; we discuss the results, strengths and shortcomings of their approaches. We also discuss new techniques the field can leverage and emerging challenges it will face while striving to build gene regulatory maps of ever-increasing resolution and comprehensiveness.
Topics: Humans; Gene Expression Regulation; Regulatory Sequences, Nucleic Acid; Genome, Human; Chromosome Mapping; DNA
PubMed: 36083269
DOI: 10.1093/hmg/ddac195