442 results match your criteria Annual Review Of Genomics And Human Genetics[Journal]


Extrachromosomal DNA in Cancer.

Annu Rev Genomics Hum Genet 2022 May 24. Epub 2022 May 24.

Department of Pathology and ChEM-H, Stanford University School of Medicine, Palo Alto, California, USA; email:

In cancer, complex genome rearrangements and other structural alterations, including the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements, drive the formation and progression of tumors. ecDNA is a particularly challenging structural alteration. By untethering oncogenes from chromosomal constraints, it elevates oncogene copy number, drives intratumoral genetic heterogeneity, promotes rapid tumor evolution, and results in treatment resistance. Read More

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The Role of Telomeres in Human Disease.

Authors:
Mary Armanios

Annu Rev Genomics Hum Genet 2022 May 24. Epub 2022 May 24.

Departments of Oncology, Genetic Medicine, Pathology, and Molecular Biology and Genetics; Telomere Center at Johns Hopkins; and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; email:

Telomere biology was first studied in maize, ciliates, yeast, and mice, and in recent decades, it has informed understanding of common disease mechanisms with broad implications for patient care. Short telomere syndromes are the most prevalent premature aging disorders, with prominent phenotypes affecting the lung and hematopoietic system. Less understood are a newly recognized group of cancer-prone syndromes that are associated with mutations that lengthen telomeres. Read More

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Five Priorities of African Genomics Research: The Next Frontier.

Annu Rev Genomics Hum Genet 2022 May 16. Epub 2022 May 16.

Faculty of Medicine and Odontostomatology, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali; email:

To embrace the prospects of accurately diagnosing thousands of monogenic conditions, predicting disease risks for complex traits or diseases, tailoring treatment to individuals' pharmacogenetic profiles, and potentially curing some diseases, research into African genomic variation is a scientific imperative. African genomes harbor millions of uncaptured variants accumulated over 300,000 years of modern humans' evolutionary history, with successive waves of admixture, migration, and natural selection combining with extensive ecological diversity to create a broad and exceptional genomic complexity. Harnessing African genomic complexity, therefore, will require sustained commitment and equitable collaboration from the scientific community and funding agencies. Read More

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Mapping Human Reproduction with Single-Cell Genomics.

Annu Rev Genomics Hum Genet 2022 May 13. Epub 2022 May 13.

Wellcome Sanger Institute, Cambridge, United Kingdom; email:

The trillions of cells in the human body develop as a result of the fusion of two extremely specialized cells: an oocyte and a sperm. This process is essential for the continuation of our species, as it ensures that parental genetic information is mixed and passed on from generation to generation. In addition to producing oocytes, the female reproductive system must provide the environment for the appropriate development of the fetus until birth. Read More

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A Journey Through Genetics to Biology.

Annu Rev Genomics Hum Genet 2022 May 13. Epub 2022 May 13.

UCL Institute of Ophthalmology, University College London, London, United Kingdom.

Although my engagement with human genetics emerged gradually, and sometimes serendipitously, it has held me spellbound for decades. Without my teachers, students, postdocs, colleagues, and collaborators, I would not be writing this review of my scientific adventures. Early gene and disease mapping was a satisfying puzzle-solving exercise, but building biological insight was my main goal. Read More

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The Genetics of Brugada Syndrome.

Annu Rev Genomics Hum Genet 2022 May 13. Epub 2022 May 13.

Leon H. Charney Division of Cardiology, Grossman School of Medicine, New York University, New York, NY, USA; email:

Brugada syndrome is a heritable channelopathy characterized by a peculiar electrocardiogram (ECG) pattern and increased risk of cardiac arrhythmias and sudden death. The arrhythmias originate because of an imbalance between the repolarizing and depolarizing currents that modulate the cardiac action potential. Even if an overt structural cardiomyopathy is not typical of Brugada syndrome, fibrosis and structural changes in the right ventricle contribute to a conduction slowing, which ultimately facilitates ventricular arrhythmias. Read More

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Ethical Guidance in Human Paleogenomics: New and Ongoing Perspectives.

Annu Rev Genomics Hum Genet 2022 May 10. Epub 2022 May 10.

Institute for Society and Genetics, Institute for Precision Health, and Division of General Internal Medicine and Health Services Research, University of California, Los Angeles, California, USA; email:

Over the past two decades, the study of ancient genomes from Ancestral humans, or human paleogenomic research, has expanded rapidly in both scale and scope. Ethical discourse has subsequently emerged to address issues of social responsibility and scientific robusticity in conducting research. Here, we highlight and contextualize the primary sources of professional ethical guidance aimed at paleogenomic researchers. Read More

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Advancing Pharmacogenomics from Single-Gene to Preemptive Testing.

Annu Rev Genomics Hum Genet 2022 May 10. Epub 2022 May 10.

Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; email:

Pharmacogenomic testing can be an effective tool to enhance medication safety and efficacy. Pharmacogenomically actionable medications are widely used, and approximately 90-95% of individuals have an actionable genotype for at least one pharmacogene. For pharmacogenomic testing to have the greatest impact on medication safety and clinical care, genetic information should be made available at the time of prescribing (preemptive testing). Read More

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Genetic Disorders of the Extracellular Matrix: From Cell and Gene Therapy to Future Applications in Regenerative Medicine.

Annu Rev Genomics Hum Genet 2022 May 10. Epub 2022 May 10.

Center for Regenerative Medicine "Stefano Ferrari," University of Modena and Reggio Emilia, Modena, Italy; email:

Metazoans have evolved to produce various types of extracellular matrix (ECM) that provide structural support, cell adhesion, cell-cell communication, and regulated exposure to external cues. Epithelial cells produce and adhere to a specialized sheet-like ECM, the basement membrane, that is critical for cellular homeostasis and tissue integrity. Mesenchymal cells, such as chondrocytes in cartilaginous tissues and keratocytes in the corneal stroma, produce a pericellular matrix that presents optimal levels of growth factors, cytokines, chemokines, and nutrients to the cell and regulates mechanosensory signals through specific cytoskeletal and cell surface receptor interactions. Read More

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The UK Biobank: A Shining Example of Genome-Wide Association Study Science with the Power to Detect the Murky Complications of Real-World Epidemiology.

Annu Rev Genomics Hum Genet 2022 May 4. Epub 2022 May 4.

Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; email:

Genome-wide association studies (GWASs) have successfully identified thousands of genetic variants that are reliably associated with human traits. Although GWASs are restricted to certain variant frequencies, they have improved our understanding of the genetic architecture of complex traits and diseases. The UK Biobank (UKBB) has brought substantial analytical opportunity and performance to association studies. Read More

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Decoding the Human Face: Progress and Challenges in Understanding the Genetics of Craniofacial Morphology.

Annu Rev Genomics Hum Genet 2022 Apr 28. Epub 2022 Apr 28.

Center for Processing Speech and Images, Department of Electrical Engineering, KU Leuven, Leuven, Belgium; email:

Variations in the form of the human face, which plays a role in our individual identities and societal interactions and exhibits extreme forms in a broad range of craniofacial syndromes and birth defects, have fascinated both geneticists and developmental biologists. Here, we review our current understanding of the genetics underlying variation in craniofacial morphology and dysmorphology, synthesizing decades of progress on Mendelian syndromes in addition to more recent results from genome-wide association studies of human facial shape and disease risk. We also discuss the various approaches used to phenotype and quantify facial shape, which are of particular importance due to the complex, multipartite nature of the craniofacial form. Read More

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Natural and Experimental Rewiring of Gene Regulatory Regions.

Annu Rev Genomics Hum Genet 2022 Apr 26. Epub 2022 Apr 26.

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; email:

The successful development and ongoing functioning of complex organisms depends on the faithful execution of the genetic code. A critical step in this process is the correct spatial and temporal expression of genes. The highly orchestrated transcription of genes is controlled primarily by regulatory elements: promoters, enhancers, and insulators. Read More

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Predicting Archaic Hominin Phenotypes from Genomic Data.

Annu Rev Genomics Hum Genet 2022 Apr 19. Epub 2022 Apr 19.

Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA; email:

Ancient DNA provides a powerful window into the biology of extant and extinct species, including humans' closest relatives: Denisovans and Neanderthals. Here, we review what is known about archaic hominin phenotypes from genomic data and how those inferences have been made. We contend that understanding the influence of variants on lower-level molecular phenotypes-such as gene expression and protein function-is a promising approach to using ancient DNA to learn about archaic hominin traits. Read More

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Maintaining Transcriptional Specificity Through Mitosis.

Annu Rev Genomics Hum Genet 2022 Apr 19. Epub 2022 Apr 19.

Institute for Regenerative Medicine and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; email:

Virtually all cell types have the same DNA, yet each type exhibits its own cell-specific pattern of gene expression. During the brief period of mitosis, the chromosomes exhibit changes in protein composition and modifications, a marked condensation, and a consequent reduction in transcription. Yet as cells exit mitosis, they reactivate their cell-specific programs with high fidelity. Read More

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Obtaining Complete Human Proteomes.

Annu Rev Genomics Hum Genet 2022 Apr 19. Epub 2022 Apr 19.

Novo Nordisk Foundation Center for Protein Research, Proteomics Program, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; email:

Proteins are the molecular effectors of the information encoded in the genome. Proteomics aims at understanding the molecular functions of proteins in their biological context. In contrast to transcriptomics and genomics, the study of proteomes provides deeper insight into the dynamic regulatory layers encoded at the protein level, such as posttranslational modifications, subcellular localization, cell signaling, and protein-protein interactions. Read More

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Diverse Molecular Mechanisms Underlying Pathogenic Protein Mutations: Beyond the Loss-of-Function Paradigm.

Annu Rev Genomics Hum Genet 2022 Apr 8. Epub 2022 Apr 8.

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom; email:

Most known disease-causing mutations occur in protein-coding regions of DNA. While some of these involve a loss of protein function (e.g. Read More

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Genome-Wide Analysis of Human Long Noncoding RNAs: A Provocative Review.

Annu Rev Genomics Hum Genet 2022 Apr 8. Epub 2022 Apr 8.

Earlham Institute, Norwich, United Kingdom; email:

Do long noncoding RNAs (lncRNAs) contribute little or substantively to human biology? To address how lncRNA loci and their transcripts, structures, interactions, and functions contribute to human traits and disease, we adopt a genome-wide perspective. We intend to provoke alternative interpretation of questionable evidence and thorough inquiry into unsubstantiated claims. We discuss pitfalls of lncRNA experimental and computational methods as well as opposing interpretations of their results. Read More

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Equity in Genomic Medicine.

Annu Rev Genomics Hum Genet 2022 Apr 1. Epub 2022 Apr 1.

Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA; email:

Since the completion of the Human Genome Project, considerable progress has been made in translating knowledge about the genetic basis of disease risk and treatment response into clinical services and public health interventions that have greater precision. It is anticipated that more precision approaches to early detection, prevention, and treatment will be developed and will enhance equity in healthcare and outcomes among disparity populations. Reduced access to genomic medicine research, clinical services, and public health interventions has the potential to exacerbate disparities in genomic medicine. Read More

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Establishing the Medical Actionability of Genomic Variants.

Annu Rev Genomics Hum Genet 2022 Apr 1. Epub 2022 Apr 1.

Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, USA; email:

Actionability is an important concept in medicine that does not have a well-accepted standard definition, nor is there a general consensus on how to establish it. Medical actionability is often conflated with clinical utility, a related but distinct concept. This lack of clarity contributes to practice variation and inconsistent coverage decisions in genomic medicine, leading to the potential for systematic bias in the use of evidence-based interventions. Read More

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The Next Frontier in Noninvasive Prenatal Diagnostics: Cell-Free Fetal DNA Analysis for Monogenic Disease Assessment.

Annu Rev Genomics Hum Genet 2022 Feb 22. Epub 2022 Feb 22.

Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong, China; email:

With the widespread clinical adoption of noninvasive screening for fetal chromosomal aneuploidies based on cell-free DNA analysis from maternal plasma, more researchers are turning their attention to noninvasive prenatal assessment for single-gene disorders. The development of a spectrum of approaches to analyze cell-free DNA in maternal circulation, including relative mutation dosage, relative haplotype dosage, and size-based methods, has expanded the scope of noninvasive prenatal testing to sex-linked and autosomal recessive disorders. Cell-free fetal DNA analysis for several of the more prevalent single-gene disorders has recently been introduced into clinical service. Read More

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February 2022

Population Screening in Health Systems.

Authors:
Marc S Williams

Annu Rev Genomics Hum Genet 2022 Feb 17. Epub 2022 Feb 17.

Genomic Medicine Institute, Geisinger, Danville, Pennsylvania, USA; email:

Applications of genomics to population screening are expanding in the United States and internationally. Many of these programs are being implemented in the context of healthcare systems, mostly in a clinical research setting, but there are some emerging examples of clinical models. This review examines these genomic population screening programs to identify common features and differences in screened conditions, genomic technology employed, approach to results disclosure, health outcomes, financial models, and sustainability. Read More

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February 2022

Heart Development and Congenital Structural Heart Defects.

Annu Rev Genomics Hum Genet 2021 08 1;22:257-284. Epub 2021 Jun 1.

Université de Paris, 75015 Paris, France.

Congenital heart disease is the most frequent birth defect and the leading cause of death for the fetus and in the first year of life. The wide phenotypic diversity of congenital heart defects requires expert diagnosis and sophisticated repair surgery. Although these defects have been described since the seventeenth century, it was only in 2005 that a consensus international nomenclature was adopted, followed by an international classification in 2017 to help provide better management of patients. Read More

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The Role of Electronic Health Records in Advancing Genomic Medicine.

Annu Rev Genomics Hum Genet 2021 08 26;22:219-238. Epub 2021 May 26.

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA; email:

Recent advances in genomic technology and widespread adoption of electronic health records (EHRs) have accelerated the development of genomic medicine, bringing promising research findings from genome science into clinical practice. Genomic and phenomic data, accrued across large populations through biobanks linked to EHRs, have enabled the study of genetic variation at a phenome-wide scale. Through new quantitative techniques, pleiotropy can be explored with phenome-wide association studies, the occurrence of common complex diseases can be predicted using the cumulative influence of many genetic variants (polygenic risk scores), and undiagnosed Mendelian syndromes can be identified using EHR-based phenotypic signatures (phenotype risk scores). Read More

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Avoiding Extinction: Recent Advances in Understanding Mechanisms of Mitochondrial DNA Purifying Selection in the Germline.

Annu Rev Genomics Hum Genet 2021 08 26;22:55-80. Epub 2021 May 26.

Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5G 1M1, Canada; email:

Mitochondria are unusual organelles in that they contain their own genomes, which are kept apart from the rest of the DNA in the cell. While mitochondrial DNA (mtDNA) is essential for respiration and most multicellular life, maintaining a genome outside the nucleus brings with it a number of challenges. Chief among these is preserving mtDNA genomic integrity from one generation to the next. Read More

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Brain Somatic Mutation in Aging and Alzheimer's Disease.

Annu Rev Genomics Hum Genet 2021 08 12;22:239-256. Epub 2021 May 12.

Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts 02115, USA; email:

Somatic mutations arise postzygotically, producing genetic differences between cells in an organism. Well established as a driver of cancer, somatic mutations also exist in nonneoplastic cells, including in the brain. Technological advances in nucleic acid sequencing have enabled recent breakthroughs that illuminate the roles of somatic mutations in aging and degenerative diseases of the brain. Read More

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Transcriptional Regulation by (Super)Enhancers: From Discovery to Mechanisms.

Annu Rev Genomics Hum Genet 2021 08 5;22:127-146. Epub 2021 May 5.

Department of Cell Biology, Erasmus MC, 3000 CA Rotterdam, The Netherlands; email:

Accurate control of gene expression in the right cell at the right moment is of fundamental importance to animal development and homeostasis. At the heart of gene regulation lie the enhancers, a class of gene regulatory elements that ensures precise spatiotemporal activation of gene transcription. Mammalian genomes are littered with enhancers, which are frequently organized in cooperative clusters such as locus control regions and superenhancers. Read More

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A Long, Fulfilling Career in Human Genetics.

Authors:
Haig H Kazazian

Annu Rev Genomics Hum Genet 2021 08 4;22:27-53. Epub 2021 May 4.

Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

I have been fortunate and privileged to have participated in amazing breakthroughs in human genetics since the 1960s. I was lucky to have trained in medical school at Dartmouth and Johns Hopkins, in pediatrics at the University of Minnesota and Johns Hopkins, and in genetics and molecular biology with Dr. Barton Childs at Johns Hopkins and Dr. Read More

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Therapeutic Opportunities of Targeting Canonical and Noncanonical PcG/TrxG Functions in Acute Myeloid Leukemia.

Annu Rev Genomics Hum Genet 2021 08 30;22:103-125. Epub 2021 Apr 30.

Leukaemia and Stem Cell Biology Group, School of Cancer and Pharmaceutical Sciences, King's College London, London SE5 9NU, United Kingdom; email:

Transcriptional deregulation is a key driver of acute myeloid leukemia (AML), a heterogeneous blood cancer with poor survival rates. Polycomb group (PcG) and Trithorax group (TrxG) genes, originally identified in several decades ago as master regulators of cellular identity and epigenetic memory, not only are important in mammalian development but also play a key role in AML disease biology. In addition to their classical canonical antagonistic transcriptional functions, noncanonical synergistic and nontranscriptional functions of PcG and TrxG are emerging. Read More

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The Need for a Human Pangenome Reference Sequence.

Annu Rev Genomics Hum Genet 2021 08 30;22:81-102. Epub 2021 Apr 30.

Department of Genetics, Edison Family Center for Genome Sciences and Systems Biology, and McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

The reference human genome sequence is inarguably the most important and widely used resource in the fields of human genetics and genomics. It has transformed the conduct of biomedical sciences and brought invaluable benefits to the understanding and improvement of human health. However, the commonly used reference sequence has profound limitations, because across much of its span, it represents the sequence of just one human haplotype. Read More

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Threespine Stickleback: A Model System For Evolutionary Genomics.

Annu Rev Genomics Hum Genet 2021 08 28;22:357-383. Epub 2021 Apr 28.

Department of Ecology and Evolution, Stony Brook University, Stony Brook, New York 11794, USA; email:

The repeated adaptation of oceanic threespine sticklebacks to fresh water has made it a premier organism to study parallel evolution. These small fish have multiple distinct ecotypes that display a wide range of diverse phenotypic traits. Ecotypes are easily crossed in the laboratory, and families are large and develop quickly enough for quantitative trait locus analyses, positioning the threespine stickleback as a versatile model organism to address a wide range of biological questions. Read More

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