402 results match your criteria Annual review of genomics and human genetics[Journal]


Pangenome Graphs.

Annu Rev Genomics Hum Genet 2020 May 26. Epub 2020 May 26.

Genomics Institute, University of California, Santa Cruz, California 95064, USA; email:

Low-cost whole-genome assembly has enabled the collection of haplotype-resolved pangenomes for numerous organisms. In turn, this technological change is encouraging the development of methods that can precisely address the sequence and variation described in large collections of related genomes. These approaches often use graphical models of the pangenome to support algorithms for sequence alignment, visualization, functional genomics, and association studies. Read More

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http://dx.doi.org/10.1146/annurev-genom-120219-080406DOI Listing
May 2020
8.957 Impact Factor

Enhancer Predictions and Genome-Wide Regulatory Circuits.

Annu Rev Genomics Hum Genet 2020 May 22. Epub 2020 May 22.

Sloan Kettering Institute, New York, NY 10065, USA; email:

Spatiotemporal control of gene expression during development requires orchestrated activities of numerous enhancers, which are -regulatory DNA sequences that, when bound by transcription factors, support selective activation or repression of associated genes. Proper activation of enhancers is critical during embryonic development, adult tissue homeostasis, and regeneration, and inappropriate enhancer activity is often associated with pathological conditions such as cancer. Multiple consortia [e. Read More

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http://dx.doi.org/10.1146/annurev-genom-121719-010946DOI Listing

The Laminopathies and the Insights They Provide into the Structural and Functional Organization of the Nucleus.

Annu Rev Genomics Hum Genet 2020 May 19. Epub 2020 May 19.

Regenerative and Developmental Biology Group, Institute of Medical Biology, Singapore 138648; email:

In recent years, our perspective on the cell nucleus has evolved from the view that it is a passive but permeable storage organelle housing the cell's genetic material to an understanding that it is in fact a highly organized, integrative, and dynamic regulatory hub. In particular, the subcompartment at the nuclear periphery, comprising the nuclear envelope and the underlying lamina, is now known to be a critical nexus in the regulation of chromatin organization, transcriptional output, biochemical and mechanosignaling pathways, and, more recently, cytoskeletal organization. We review the various functional roles of the nuclear periphery and their deregulation in diseases of the nuclear envelope, specifically the laminopathies, which, despite their rarity, provide insights into contemporary health-care issues. Read More

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http://dx.doi.org/10.1146/annurev-genom-121219-083616DOI Listing

Progress, Challenges, and Surprises in Annotating the Human Genome.

Annu Rev Genomics Hum Genet 2020 May 18. Epub 2020 May 18.

European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton CB10 1SD, United Kingdom; email:

Our understanding of the human genome has continuously expanded since its draft publication in 2001. Over the years, novel assays have allowed us to progressively overlay layers of knowledge above the raw sequence of A's, T's, G's, and C's. The reference human genome sequence is now a complex knowledge base maintained under the shared stewardship of multiple specialist communities. Read More

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http://dx.doi.org/10.1146/annurev-genom-121119-083418DOI Listing

Genomically Aided Diagnosis of Severe Developmental Disorders.

Annu Rev Genomics Hum Genet 2020 May 18. Epub 2020 May 18.

Department of Clinical Genetics, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; email:

Our ability to make accurate and specific genetic diagnoses in individuals with severe developmental disorders has been transformed by data derived from genomic sequencing technologies. These data reveal both the patterns and rates of different mutational mechanisms and identify regions of the human genome with fewer mutations than would be expected. In outbred populations, the most common identifiable cause of severe developmental disorders is de novo mutation affecting the coding region in one of approximately 500 different genes, almost universally showing constraint. Read More

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http://dx.doi.org/10.1146/annurev-genom-120919-082329DOI Listing

Cell Lineage Tracing and Cellular Diversity in Humans.

Annu Rev Genomics Hum Genet 2020 May 15. Epub 2020 May 15.

Child Study Center, Yale University, New Haven, Connecticut 06520, USA; email:

Tracing cell lineages is fundamental for understanding the rules governing development in multicellular organisms and delineating complex biological processes involving the differentiation of multiple cell types with distinct lineage hierarchies. In humans, experimental lineage tracing is unethical, and one has to rely on natural-mutation markers that are created within cells as they proliferate and age. Recent studies have demonstrated that it is now possible to trace lineages in normal, noncancerous cells with a variety of data types using natural variations in the nuclear and mitochondrial DNA as well as variations in DNA methylation status. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015241DOI Listing

Recent Advances in Understanding the Genetic Architecture of Autism.

Annu Rev Genomics Hum Genet 2020 May 12. Epub 2020 May 12.

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

Recent advances in understanding the genetic architecture of autism spectrum disorder have allowed for unprecedented insight into its biological underpinnings. New studies have elucidated the contributions of a variety of forms of genetic variation to autism susceptibility. While the roles of de novo copy number variants and single-nucleotide variants-causing loss-of-function or missense changes-have been increasingly recognized and refined, mosaic single-nucleotide variants have been implicated more recently in some cases. Read More

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http://dx.doi.org/10.1146/annurev-genom-121219-082309DOI Listing

The Genetics of Epilepsy.

Annu Rev Genomics Hum Genet 2020 Apr 27. Epub 2020 Apr 27.

Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria 3084, Australia; email:

Epilepsy encompasses a group of heterogeneous brain diseases that affect more than 50 million people worldwide. Epilepsy may have discernible structural, infectious, metabolic, and immune etiologies; however, in most people with epilepsy, no obvious cause is identifiable. Based initially on family studies and later on advances in gene sequencing technologies and computational approaches, as well as the establishment of large collaborative initiatives, we now know that genetics plays a much greater role in epilepsy than was previously appreciated. Read More

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http://dx.doi.org/10.1146/annurev-genom-120219-074937DOI Listing

Using Single-Cell and Spatial Transcriptomes to Understand Stem Cell Lineage Specification During Early Embryo Development.

Annu Rev Genomics Hum Genet 2020 Apr 27. Epub 2020 Apr 27.

Center of Cell Lineage and Atlas, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, China.

Embryonic development and stem cell differentiation provide a paradigm to understand the molecular regulation of coordinated cell fate determination and the architecture of tissue patterning. Emerging technologies such as single-cell RNA sequencing and spatial transcriptomics are opening new avenues to dissect cell organization, the divergence of morphological and molecular properties, and lineage allocation. Rapid advances in experimental and computational tools have enabled researchers to make many discoveries and revisit old hypotheses. Read More

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http://dx.doi.org/10.1146/annurev-genom-120219-083220DOI Listing

Genomic Data Sharing for Novel Mendelian Disease Gene Discovery: The Matchmaker Exchange.

Annu Rev Genomics Hum Genet 2020 Apr 27. Epub 2020 Apr 27.

McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA; email:

In the last decade, exome and/or genome sequencing has become a common test in the diagnosis of individuals with features of a rare Mendelian disorder. Despite its success, this test leaves the majority of tested individuals undiagnosed. This review describes the Matchmaker Exchange (MME), a federated network established to facilitate the solving of undiagnosed rare-disease cases through data sharing. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-014915DOI Listing

RNA Conformation Capture by Proximity Ligation.

Annu Rev Genomics Hum Genet 2020 Apr 22. Epub 2020 Apr 22.

Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, United Kingdom.

RNA proximity ligation is a set of molecular biology techniques used to analyze the conformations and spatial proximity of RNA molecules within cells. A typical experiment starts with cross-linking of a biological sample using UV light or psoralen, followed by partial fragmentation of RNA, RNA-RNA ligation, library preparation, and high-throughput sequencing. In the past decade, proximity ligation has been used to study structures of individual RNAs, networks of interactions between small RNAs and their targets, and whole RNA-RNA interactomes, in models ranging from bacteria to animal tissues and whole animals. Read More

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http://dx.doi.org/10.1146/annurev-genom-120219-073756DOI Listing

Population Screening for Inherited Predisposition to Breast and Ovarian Cancer.

Annu Rev Genomics Hum Genet 2020 Apr 21. Epub 2020 Apr 21.

Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel; email:

The discovery of genes underlying inherited predisposition to breast and ovarian cancer has revolutionized the ability to identify women at high risk for these diseases before they become affected. Women who are carriers of deleterious variants in these genes can undertake surveillance and prevention measures that have been shown to reduce morbidity and mortality. However, under current strategies, the vast majority of women carriers remain undetected until they become affected. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015253DOI Listing

Pedigrees and Perpetrators: Uses of DNA and Genealogy in Forensic Investigations.

Authors:
Sara H Katsanis

Annu Rev Genomics Hum Genet 2020 Apr 14. Epub 2020 Apr 14.

Mary Ann & J. Milburn Smith Child Health Research, Outreach, and Advocacy Center, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA; email:

In the past few years, cases with DNA evidence that could not be solved with direct matches in DNA databases have benefited from comparing single-nucleotide polymorphism data with private and public genomic databases. Using a combination of genome comparisons and traditional genealogical research, investigators can triangulate distant relatives to the contributor of DNA data from a crime scene, ultimately identifying perpetrators of violent crimes. This approach has also been successful in identifying unknown deceased persons and perpetrators of lesser crimes. Read More

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http://dx.doi.org/10.1146/annurev-genom-111819-084213DOI Listing

How Natural Genetic Variation Shapes Behavior.

Annu Rev Genomics Hum Genet 2020 Apr 13. Epub 2020 Apr 13.

Zuckerman Mind Brain Behavior Institute and Department of Ecology, Evolution, and Environmental Biology, Columbia University, New York, NY 10027, USA; email:

Nervous systems allow animals to acutely respond and behaviorally adapt to changes and recurring patterns in their environment at multiple timescales-from milliseconds to years. Behavior is further shaped at intergenerational timescales by genetic variation, drift, and selection. This sophistication and flexibility of behavior makes it challenging to measure behavior consistently in individual subjects and to compare it across individuals. Read More

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http://dx.doi.org/10.1146/annurev-genom-111219-080427DOI Listing

New Diagnostic Approaches for Undiagnosed Rare Genetic Diseases.

Annu Rev Genomics Hum Genet 2020 Apr 13. Epub 2020 Apr 13.

CHEO Research Institute, University of Ottawa, Ottawa, Ontario K1H 5B2, Canada; email:

Accurate diagnosis is the cornerstone of medicine; it is essential for informed care and promoting patient and family well-being. However, families with a rare genetic disease (RGD) often spend more than five years on a diagnostic odyssey of specialist visits and invasive testing that is lengthy, costly, and often futile, as 50% of patients do not receive a molecular diagnosis. The current diagnostic paradigm is not well designed for RGDs, especially for patients who remain undiagnosed after the initial set of investigations, and thus requires an expansion of approaches in the clinic. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015345DOI Listing

Cultivating DNA Sequencing Technology After the Human Genome Project.

Annu Rev Genomics Hum Genet 2020 Apr 13. Epub 2020 Apr 13.

Boreal Genomics, Vancouver, British Columbia V6T 1Z3, Canada.

When the Human Genome Project was completed in 2003, automated Sanger DNA sequencing with fluorescent dye labels was the dominant technology. Several nascent alternative methods based on older ideas that had not been fully developed were the focus of technical researchers and companies. Funding agencies recognized the dynamic nature of technology development and that, beyond the Human Genome Project, there were growing opportunities to deploy DNA sequencing in biological research. Read More

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http://dx.doi.org/10.1146/annurev-genom-111919-082433DOI Listing
April 2020
8.957 Impact Factor

The Genomics and Genetics of Oxygen Homeostasis.

Authors:
Gregg L Semenza

Annu Rev Genomics Hum Genet 2020 Apr 7. Epub 2020 Apr 7.

Departments of Genetic Medicine, Oncology, Pediatrics, Radiation Oncology, Medicine, and Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

Human survival is dependent upon the continuous delivery of O to each cell in the body in sufficient amounts to meet metabolic requirements, primarily for ATP generation by oxidative phosphorylation. Hypoxia-inducible factors (HIFs) regulate the transcription of thousands of genes to balance O supply and demand. The HIFs are negatively regulated by O-dependent hydroxylation and ubiquitination by prolyl hydroxylase domain (PHD) proteins and the von Hippel-Lindau (VHL) protein. Read More

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http://dx.doi.org/10.1146/annurev-genom-111119-073356DOI Listing

Models of Technology Transfer for Genome-Editing Technologies.

Annu Rev Genomics Hum Genet 2020 Mar 9. Epub 2020 Mar 9.

Edmond J. Safra Center for Ethics, Harvard University, Cambridge, Massachusetts 02138, USA; email:

Many of the fundamental inventions of genome editing, including meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR, were first made at universities and patented to encourage commercial development. This gave rise to a diversity of technology transfer models but also conflicts among them. Against a broader historical and policy backdrop of university patenting and special challenges concerning research tools, we review the patent estates of genome editing and the diversity of technology transfer models employed to commercialize them, including deposit in the public domain, open access contracts, material transfer agreements, nonexclusive and exclusive licenses, surrogate licenses, and aggregated licenses. Read More

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http://dx.doi.org/10.1146/annurev-genom-121119-100145DOI Listing

The Long Journey from Diagnosis to Therapy.

Authors:
Kay E Davies

Annu Rev Genomics Hum Genet 2020 Mar 2. Epub 2020 Mar 2.

MDUK Oxford Neuromuscular Centre, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom; email:

I was honored to be asked by the Editorial Committee of the to write an autobiographical account of my life in science and in genetics in particular. The field has moved from mapping Mendelian disorders 40 years ago to the delivery of effective therapies for some monogenic disorders today. My 40-year journey from diagnosis to therapy for Duchenne muscular dystrophy has depended on collaborations among basic scientists, clinicians, medical charities, genetic counselors, biotech companies, and affected families. Read More

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http://dx.doi.org/10.1146/annurev-genom-112019-083518DOI Listing

Twenty-Five Years of Spinal Muscular Atrophy Research: From Phenotype to Genotype to Therapy, and What Comes Next.

Annu Rev Genomics Hum Genet 2020 Jan 31. Epub 2020 Jan 31.

Institute of Human Genetics, Center for Molecular Medicine Cologne and Center for Rare Diseases, University Hospital of Cologne, University of Cologne, 50931 Cologne, Germany; email:

Twenty-five years ago, the underlying genetic cause for one of the most common and devastating inherited diseases in humans, spinal muscular atrophy (SMA), was identified. Homozygous deletions or, rarely, subtle mutations of cause SMA, and the copy number of the nearly identical copy gene inversely correlates with disease severity. SMA has become a paradigm and a prime example of a monogenic neurological disorder that can be efficiently ameliorated or nearly cured by novel therapeutic strategies, such as antisense oligonucleotide or gene replacement therapy. Read More

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http://dx.doi.org/10.1146/annurev-genom-102319-103602DOI Listing
January 2020

Looking Beyond GINA: Policy Approaches to Address Genetic Discrimination.

Annu Rev Genomics Hum Genet 2020 Jan 21. Epub 2020 Jan 21.

Brandeis School of Law and School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.

Genetic discrimination (GD) is consistently associated with research and innovation in genetics. Over recent decades, countries around the world have attempted to address GD using various policy measures. In this article, we survey these approaches and provide a critical commentary on their advantages and disadvantages. Read More

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http://dx.doi.org/10.1146/annurev-genom-111119-011436DOI Listing
January 2020

The Regulation of Mitochondrial Replacement Techniques Around the World.

Annu Rev Genomics Hum Genet 2020 Jan 21. Epub 2020 Jan 21.

Bioethics Programs, Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Quebec H3C 3J7, Canada; email:

Mitochondrial replacement techniques (MRTs, also referred to as mitochondrial replacement therapies) have given hope to many women who wish to have genetically related children but have mitochondrial DNA mutations in their eggs. MRTs have also spurred deep ethical disagreemensts and led to different regulatory approaches worldwide. In this review, we discuss the current regulation of MRTs across several countries. Read More

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http://dx.doi.org/10.1146/annurev-genom-111119-101815DOI Listing
January 2020

An Accidental Genetic Epidemiologist.

Authors:
Robert C Elston

Annu Rev Genomics Hum Genet 2020 Jan 14. Epub 2020 Jan 14.

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA; email:

I briefly describe my early life and how, through a series of serendipitous events, I became a genetic epidemiologist. I discuss how the Elston-Stewart algorithm was discovered and its contribution to segregation, linkage, and association analysis. New linkage findings and paternity testing resulted from having a genotyping lab. Read More

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http://dx.doi.org/10.1146/annurev-genom-103119-125052DOI Listing
January 2020

Thinking About the Evolution of Complex Traits in the Era of Genome-Wide Association Studies.

Annu Rev Genomics Hum Genet 2019 08 5;20:461-493. Epub 2019 Jul 5.

Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria; email:

Many traits of interest are highly heritable and genetically complex, meaning that much of the variation they exhibit arises from differences at numerous loci in the genome. Complex traits and their evolution have been studied for more than a century, but only in the last decade have genome-wide association studies (GWASs) in humans begun to reveal their genetic basis. Here, we bring these threads of research together to ask how findings from GWASs can further our understanding of the processes that give rise to heritable variation in complex traits and of the genetic basis of complex trait evolution in response to changing selection pressures (i. Read More

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http://dx.doi.org/10.1146/annurev-genom-083115-022316DOI Listing

The Genetics of Human Skin and Hair Pigmentation.

Annu Rev Genomics Hum Genet 2019 08 17;20:41-72. Epub 2019 May 17.

Dermatology Research Centre, The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Queensland 4102, Australia; email:

Human skin and hair color are visible traits that can vary dramatically within and across ethnic populations. The genetic makeup of these traits-including polymorphisms in the enzymes and signaling proteins involved in melanogenesis, and the vital role of ion transport mechanisms operating during the maturation and distribution of the melanosome-has provided new insights into the regulation of pigmentation. A large number of novel loci involved in the process have been recently discovered through four large-scale genome-wide association studies in Europeans, two large genetic studies of skin color in Africans, one study in Latin Americans, and functional testing in animal models. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015230DOI Listing
August 2019
1 Read

Massively Parallel Assays and Quantitative Sequence-Function Relationships.

Annu Rev Genomics Hum Genet 2019 08 15;20:99-127. Epub 2019 May 15.

Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA; email:

Over the last decade, a rich variety of massively parallel assays have revolutionized our understanding of how biological sequences encode quantitative molecular phenotypes. These assays include deep mutational scanning, high-throughput SELEX, and massively parallel reporter assays. Here, we review these experimental methods and how the data they produce can be used to quantitatively model sequence-function relationships. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-014845DOI Listing
August 2019
1 Read

tRNA Metabolism and Neurodevelopmental Disorders.

Annu Rev Genomics Hum Genet 2019 08 13;20:359-387. Epub 2019 May 13.

Department of Genetics and Genome Sciences and Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, Ohio 44106, USA; email:

tRNAs are short noncoding RNAs required for protein translation. The human genome includes more than 600 putative tRNA genes, many of which are considered redundant. tRNA transcripts are subject to tightly controlled, multistep maturation processes that lead to the removal of flanking sequences and the addition of nontemplated nucleotides. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716996PMC
August 2019
1 Read

Genetic Predisposition to Childhood Cancer in the Genomic Era.

Annu Rev Genomics Hum Genet 2019 08 13;20:241-263. Epub 2019 May 13.

Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA; email:

Developments over the past five years have significantly advanced our ability to use genome-scale analyses-including high-density genotyping, transcriptome sequencing, exome sequencing, and genome sequencing-to identify the genetic basis of childhood cancer. This article reviews several key results from an expanding number of genomic studies of pediatric cancer: () Histopathologic subtypes of cancers can be associated with a high incidence of germline predisposition, () neurodevelopmental disorders or highly penetrant cancer predisposition syndromes can result from specific patterns of variation in genes encoding the SMARC family of chromatin remodelers, () genome-wide association studies with relatively small pediatric cancer cohorts have successfully identified single-nucleotide polymorphisms with large effect sizes and provided insight into population differences in cancer risk, and () multiple exome or genome analyses of unselected childhood cancer cohorts have yielded a 7-10% incidence of pathogenic variants in cancer predisposition genes. This work supports the increasing use of genomic sequencing in the care of pediatric cancer patients and at-risk family members. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015415DOI Listing
August 2019
5 Reads

The Causes and Consequences of Genetic Interactions (Epistasis).

Annu Rev Genomics Hum Genet 2019 08 13;20:433-460. Epub 2019 May 13.

Systems Biology Program, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; email:

The same mutation can have different effects in different individuals. One important reason for this is that the outcome of a mutation can depend on the genetic context in which it occurs. This dependency is known as epistasis. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-014857DOI Listing
August 2019
2 Reads

Measuring Clonal Evolution in Cancer with Genomics.

Annu Rev Genomics Hum Genet 2019 08 5;20:309-329. Epub 2019 May 5.

Evolution and Cancer Laboratory, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom; email:

Cancers originate from somatic cells in the human body that have accumulated genetic alterations. These mutations modify the phenotype of the cells, allowing them to escape the homeostatic regulation that maintains normal cell number. Viewed through the lens of evolutionary biology, the transformation of normal cells into malignant cells is evolution in action. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021712DOI Listing
August 2019
3 Reads

Consanguinity and Inbreeding in Health and Disease in North African Populations.

Annu Rev Genomics Hum Genet 2019 08 30;20:155-179. Epub 2019 Apr 30.

Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, 1002 Tunis Belvédère, Tunisia; email:

North Africa is defined as the geographical region separated from the rest of the continent by the Sahara and from Europe by the Mediterranean Sea. The main demographic features of North African populations are their familial structure and high rates of familial and geographic endogamy, which have a proven impact on health, particularly the occurrence of genetic diseases, with a greater effect on the frequency and spectrum of the rarest forms of autosomal recessive genetic diseases. More than 500 different genetic diseases have been reported in this region, most of which are autosomal recessive. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-014954DOI Listing
August 2019
1 Read

Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases.

Annu Rev Genomics Hum Genet 2019 08 24;20:201-216. Epub 2019 Apr 24.

Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, RIKEN, Kobe, Hyogo 650-0047, Japan; email:

Given the importance of visual information to many daily activities, retinal degenerative diseases-which include both inherited conditions (such as retinitis pigmentosa) and acquired conditions (such as age-related macular degeneration)-can have a dramatic impact on human lives. The therapeutic options for these diseases remain limited. Since the discovery of the first causal gene for retinitis pigmentosa almost three decades ago, more than 250 genes have been identified, and gene therapies have been rapidly developed. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015043DOI Listing
August 2019
1 Read

Genetic Etiologies, Diagnosis, and Treatment of Tuberous Sclerosis Complex.

Annu Rev Genomics Hum Genet 2019 08 24;20:217-240. Epub 2019 Apr 24.

F.M. Kirby Neurobiology Center, Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; email:

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects multiple organ systems due to an inactivating variant in either or , resulting in the hyperactivation of the mechanistic target of rapamycin (mTOR) pathway. Dysregulated mTOR signaling results in increased cell growth and proliferation. Clinically, TSC patients exhibit great phenotypic variability, but the neurologic and neuropsychiatric manifestations of the disease have the greatest morbidity and mortality. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015354DOI Listing
August 2019
3 Reads

The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy.

Annu Rev Genomics Hum Genet 2019 08 24;20:265-291. Epub 2019 Apr 24.

Department of Pharmacology, School of Medicine, University of Nevada, Reno, Nevada 89557, USA; email:

Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, provides a powerful model of the complex interplay between genetic and epigenetic mechanisms of chromatin regulation. FSHD is caused by dysregulation of a macrosatellite repeat, either by contraction of the repeat or by mutations in silencing proteins. Both cases lead to chromatin relaxation and, in the context of a permissive allele, aberrant expression of the gene in skeletal muscle. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-genom-0831
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http://dx.doi.org/10.1146/annurev-genom-083118-014933DOI Listing
August 2019
16 Reads

The Status and Impact of Clinical Tumor Genome Sequencing.

Annu Rev Genomics Hum Genet 2019 08 17;20:413-432. Epub 2019 Apr 17.

Khalifa Bin Zayed Institute for Personalized Cancer Therapy and Sheikh Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; email:

Since the discovery that DNA alterations initiate tumorigenesis, scientists and clinicians have been exploring ways to counter these changes with targeted therapeutics. The sequencing of tumor DNA was initially limited to highly actionable hot spots-areas of the genome that are frequently altered and have an approved matched therapy in a specific tumor type. Large-scale genome sequencing programs quickly developed technological improvements that enabled the deployment of whole-exome and whole-genome sequencing technologies at scale for pristine sample materials in research environments. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015034DOI Listing
August 2019
2 Reads

Roles of Extracellular Vesicles in High-Grade Gliomas: Tiny Particles with Outsized Influence.

Authors:
Michael W Graner

Annu Rev Genomics Hum Genet 2019 08 12;20:331-357. Epub 2019 Apr 12.

Department of Neurosurgery, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado 80045, USA; email:

High-grade gliomas, particularly glioblastomas (grade IV), are devastating diseases with dismal prognoses; afflicted patients seldom live longer than 15 months, and their quality of life suffers immensely. Our current standard-of-care therapy has remained essentially unchanged for almost 15 years, with little new therapeutic progress. We desperately need a better biologic understanding of these complicated tumors in a complicated organ. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717010PMC
August 2019
8 Reads

The Future of Genomic Studies Must Be Globally Representative: Perspectives from PAGE.

Annu Rev Genomics Hum Genet 2019 08 12;20:181-200. Epub 2019 Apr 12.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; email:

The past decade has seen a technological revolution in human genetics that has empowered population-level investigations into genetic associations with phenotypes. Although these discoveries rely on genetic variation across individuals, association studies have overwhelmingly been performed in populations of European descent. In this review, we describe limitations faced by single-population studies and provide an overview of strategies to improve global representation in existing data sets and future human genomics research via diversity-focused, multiethnic studies. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012212PMC
August 2019
4 Reads

Advances in the Genetic Basis and Pathogenesis of Sarcomere Cardiomyopathies.

Annu Rev Genomics Hum Genet 2019 08 12;20:129-153. Epub 2019 Apr 12.

Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; email:

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are common heart muscle disorders that are caused by pathogenic variants in sarcomere protein genes. HCM is characterized by unexplained cardiac hypertrophy (increased chamber wall thickness) that is accompanied by enhanced cardiac contractility and impaired relaxation. DCM is defined as increased ventricular chamber volume with contractile impairment. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-genom-0831
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http://dx.doi.org/10.1146/annurev-genom-083118-015306DOI Listing
August 2019
17 Reads

Epigenetic Regulation and Risk Factors During the Development of Human Gametes and Early Embryos.

Annu Rev Genomics Hum Genet 2019 08 27;20:21-40. Epub 2019 Mar 27.

Beijing Advanced Innovation Center for Genomics, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; email:

Drastic epigenetic reprogramming occurs during human gametogenesis and early embryo development. Advances in low-input and single-cell epigenetic techniques have provided powerful tools to dissect the genome-wide dynamics of different epigenetic molecular layers in these processes. In this review, we focus mainly on the most recent progress in understanding the dynamics of DNA methylation, chromatin accessibility, and histone modifications in human gametogenesis and early embryo development. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015143DOI Listing
August 2019
3 Reads

Genomic Research Through an Indigenous Lens: Understanding the Expectations.

Annu Rev Genomics Hum Genet 2019 08 20;20:495-517. Epub 2019 Mar 20.

Native Nations Institute, Udall Center for Studies in Public Policy, University of Arizona, Tucson, Arizona 85719, USA; email:

Indigenous scholars are leading initiatives to improve access to genetic and genomic research and health care based on their unique cultural contexts and within sovereign-based governance models created and accepted by their peoples. In the past, Indigenous peoples' engagement with genomicresearch was hampered by a lack of standardized guidelines and institutional partnerships, resulting in group harms. This article provides a comparative analysis of research guidelines from Canada, New Zealand, Australia, and the United States that pertain to Indigenous peoples. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015434DOI Listing
August 2019
20 Reads

The Development of Human Genetics at the National Research Centre, Cairo, Egypt: A Story of 50 Years.

Authors:
Samia A Temtamy

Annu Rev Genomics Hum Genet 2019 08 8;20:1-19. Epub 2019 Mar 8.

Center of Excellence for Human Genetics, National Research Centre, Cairo 12622, Egypt; email:

This article describes my experiences over more than 50 years in initiating and maintaining research on human genetics and genomics at the National Research Centre in Cairo, Egypt, from its beginnings in a small unit of human genetics to the creation of the Center of Excellence for Human Genetics. This was also the subject of a lecture I gave at the 10th Conference of the African Society of Human Genetics, held in Cairo in November 2017, after which Professor Michèle Ramsay, president of the society, suggested that I write an autobiographical article for the . I hope that I succeeded in the difficult assignment of summarizing the efforts of a researcher from a developing country to initiate and maintain the rapidly advancing science of human genetics and genomics in my own country and make contributions to the worldwide scientific community. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-015201DOI Listing
August 2019
1 Read

Pregnancy Immunogenetics and Genomics: Implications for Pregnancy-Related Complications and Autoimmune Disease.

Annu Rev Genomics Hum Genet 2019 08 8;20:73-97. Epub 2019 Mar 8.

Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; email:

Pregnancy presents a singular physiological scenario during which the maternal immune system must accommodate the semiallogeneic fetus. Fluctuations between pro- and anti-inflammatory states are required throughout gestation to facilitate uterine tissue remodeling, fetal growth and development, and finally birth. Tolerance for the fetus must be established and maintained without fundamentally compromising the maternal immune system function, so that both the mother and fetus are protected from foreign insults. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-014943DOI Listing
August 2019
1 Read

Lynch Syndrome: From Screening to Diagnosis to Treatment in the Era of Modern Molecular Oncology.

Annu Rev Genomics Hum Genet 2019 08 8;20:293-307. Epub 2019 Mar 8.

Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.

Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in the mismatch repair genes and is the most common etiology of hereditary colorectal cancer. While Lynch syndrome was initially defined by the clinical Amsterdam criteria, these criteria lack the sensitivity needed for clinical utility. This review covers the evolution of screening for Lynch syndrome from the use of tumor microsatellite instability and/or somatic alterations in mismatch repair protein expression by immunohistochemistry to the newest methods using next-generation sequencing. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-genom-0831
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http://dx.doi.org/10.1146/annurev-genom-083118-015406DOI Listing
August 2019
24 Reads

Early Lessons from the Implementation of Genomic Medicine Programs.

Authors:
Marc S Williams

Annu Rev Genomics Hum Genet 2019 08 27;20:389-411. Epub 2019 Feb 27.

Genomic Medicine Institute, Geisinger, Danville, Pennsylvania 17822-2620, USA; email:

Massively parallel sequencing is emerging from research settings into clinical practice, helping the vision of precision medicine to become a reality. The most successful applications are using the tools of implementation science within the framework of the learning health-care system. This article examines the application of massively parallel sequencing to four clinical scenarios: pharmacogenomics, diagnostic testing, somatic testing for molecular tumor characterization, and population screening. Read More

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http://dx.doi.org/10.1146/annurev-genom-083118-014924DOI Listing
August 2019
1 Read

International Divergence in Gene Patenting.

Annu Rev Genomics Hum Genet 2019 08 20;20:519-541. Epub 2019 Feb 20.

Centre for IT and IP Law, KU Leuven, 3000 Leuven, Belgium.

This review explores the recent divergence in international patent law relating to genes and associated subject matter. This divergence stems primarily from decisions of the highest courts in the United States and Australia on the eligibility of patent claims relating to the gene sequences. Patent offices, courts, and policy makers have struggled for many years to clearly articulate the bounds of patent claims on isolated and synthetic DNA and related products and processes, including methods for their use in genetic diagnostics. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-genom-0831
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http://dx.doi.org/10.1146/annurev-genom-083118-015112DOI Listing
August 2019
6 Reads
8.957 Impact Factor

Common and Founder Mutations for Monogenic Traits in Sub-Saharan African Populations.

Annu Rev Genomics Hum Genet 2018 08;19:149-175

Division of Human Genetics, National Health Laboratory Service, and Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

This review highlights molecular genetic studies of monogenic traits where common pathogenic mutations occur in black families from sub-Saharan Africa. Examples of founder mutations have been identified for oculocutaneous albinism, cystic fibrosis, Fanconi anemia, and Gaucher disease. Although there are few studies from Africa, some of the mutations traverse populations across the continent, and they are almost all different from the common mutations observed in non-African populations. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021256DOI Listing
August 2018
35 Reads

The Genetics and Genomics of Asthma.

Annu Rev Genomics Hum Genet 2018 08;19:223-246

National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom; email: , ,

Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis-assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale-have substantially altered this landscape. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-genom-0831
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http://dx.doi.org/10.1146/annurev-genom-083117-021651DOI Listing
August 2018
66 Reads

Does Malnutrition Have a Genetic Component?

Annu Rev Genomics Hum Genet 2018 08 6;19:247-262. Epub 2018 Jun 6.

Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA; email:

Malnutrition is a complex disorder, defined by an imbalance, excess, or deficiency of nutrient intake. The visible signs of malnutrition are stunted growth and wasting, but malnourished children are also more likely to have delays in neurocognitive development, vaccine failure, and susceptibility to infection. Despite malnutrition being a major global health problem, we do not yet understand the pathogenesis of this complex disorder. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021340DOI Listing
August 2018
1 Read

Editing the Epigenome: Reshaping the Genomic Landscape.

Annu Rev Genomics Hum Genet 2018 08 31;19:43-71. Epub 2018 May 31.

Department of Biomedical Engineering and Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708, USA; email: ,

The eukaryotic epigenome has an instrumental role in determining and maintaining cell identity and function. Epigenetic components such as DNA methylation, histone tail modifications, chromatin accessibility, and DNA architecture are tightly correlated with central cellular processes, while their dysregulation manifests in aberrant gene expression and disease. The ability to specifically edit the epigenome holds the promise of enhancing understanding of how epigenetic modifications function and enabling manipulation of cell phenotype for research or therapeutic purposes. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021632DOI Listing
August 2018
3 Reads

Rare-Variant Studies to Complement Genome-Wide Association Studies.

Annu Rev Genomics Hum Genet 2018 08 25;19:97-112. Epub 2018 May 25.

Wellcome Sanger Institute, Cambridge CB10 1HH, United Kingdom; email:

Genome-wide association studies (GWASs) have revolutionized human disease genetics by discovering tens of thousands of associations between common variants and complex diseases. In parallel, huge technological advances in DNA sequencing have made it possible to measure and analyze rare variation in populations. This review considers these two stories and how they have come together. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021641DOI Listing
August 2018
1 Read