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


Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases.

Annu Rev Genomics Hum Genet 2019 Apr 24. 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

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

Annu Rev Genomics Hum Genet 2019 Apr 24. 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

The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy.

Annu Rev Genomics Hum Genet 2019 Apr 24. 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
April 2019
1 Read

The Status and Impact of Clinical Tumor Genome Sequencing.

Annu Rev Genomics Hum Genet 2019 Apr 17. 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

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

Authors:
Michael W Graner

Annu Rev Genomics Hum Genet 2019 Apr 12. 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
April 2019
1 Read

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

Annu Rev Genomics Hum Genet 2019 Apr 12. 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

Advances in the Genetic Basis and Pathogenesis of Sarcomere Cardiomyopathies.

Annu Rev Genomics Hum Genet 2019 Apr 12. 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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http://dx.doi.org/10.1146/annurev-genom-083118-015306DOI Listing
April 2019
2 Reads

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

Annu Rev Genomics Hum Genet 2019 Mar 27. 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

Genomic Research Through an Indigenous Lens: Understanding the Expectations.

Annu Rev Genomics Hum Genet 2019 Mar 20. 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 genomic research 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
March 2019
2 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 Mar 8. 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 Annual Review of Genomics and Human Genetics. 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

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

Annu Rev Genomics Hum Genet 2019 Mar 8. 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

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

Annu Rev Genomics Hum Genet 2019 Mar 8. 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
March 2019
5 Reads

Early Lessons from the Implementation of Genomic Medicine Programs.

Authors:
Marc S Williams

Annu Rev Genomics Hum Genet 2019 Feb 27. 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
February 2019

International Divergence in Gene Patenting.

Annu Rev Genomics Hum Genet 2019 Feb 20. 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 the patenting of genes and related 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 BRCA 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
February 2019
5 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
20 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
35 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

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
1 Read

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

Genotype Imputation from Large Reference Panels.

Annu Rev Genomics Hum Genet 2018 08 23;19:73-96. Epub 2018 May 23.

Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington 98195-7720, USA; email:

Genotype imputation has become a standard tool in genome-wide association studies because it enables researchers to inexpensively approximate whole-genome sequence data from genome-wide single-nucleotide polymorphism array data. Genotype imputation increases statistical power, facilitates fine mapping of causal variants, and plays a key role in meta-analyses of genome-wide association studies. Only variants that were previously observed in a reference panel of sequenced individuals can be imputed. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021602DOI Listing
August 2018
1 Read

The Genetics of Primary Microcephaly.

Annu Rev Genomics Hum Genet 2018 08 23;19:177-200. Epub 2018 May 23.

Division of Genetics and Genomics, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts 02115, USA.

Primary microcephaly (MCPH, for "microcephaly primary hereditary") is a disorder of brain development that results in a head circumference more than 3 standard deviations below the mean for age and gender. It has a wide variety of causes, including toxic exposures, in utero infections, and metabolic conditions. While the genetic microcephaly syndromes are relatively rare, studying these syndromes can reveal molecular mechanisms that are critical in the regulation of neural progenitor cells, brain size, and human brain evolution. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021441DOI Listing

Small-Molecule Screening for Genetic Diseases.

Annu Rev Genomics Hum Genet 2018 08 23;19:263-288. Epub 2018 May 23.

Small Molecule Discovery Center and Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, USA; email: , , ,

The genetic determinants of many diseases, including monogenic diseases and cancers, have been identified; nevertheless, targeted therapy remains elusive for most. High-throughput screening (HTS) of small molecules, including high-content analysis (HCA), has been an important technology for the discovery of molecular tools and new therapeutics. HTS can be based on modulation of a known disease target (called reverse chemical genetics) or modulation of a disease-associated mechanism or phenotype (forward chemical genetics). Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021452DOI Listing
August 2018
2 Reads

Population Screening for Hemoglobinopathies.

Annu Rev Genomics Hum Genet 2018 08 11;19:355-380. Epub 2018 May 11.

Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka; email: , ,

Hemoglobinopathies are the most common single-gene disorders in the world. Their prevalence is predicted to increase in the future, and low-income hemoglobinopathy-endemic regions need to manage most of the world's affected persons. International organizations, governments, and other stakeholders have initiated national or regional prevention programs in both endemic and nonendemic countries by performing population screening for α- and β-thalassemia, HbE disease, and sickle cell disease in neonates, adolescents, reproductive-age adults (preconceptionally or in the early antenatal period), and family members of diagnosed cases. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035451DOI Listing
August 2018
1 Read

Tales of Human Migration, Admixture, and Selection in Africa.

Annu Rev Genomics Hum Genet 2018 08 4;19:405-428. Epub 2018 May 4.

Human Evolution, Department of Organismal Biology, Uppsala University, SE-752 36 Uppsala, Sweden; email: ,

In the last three decades, genetic studies have played an increasingly important role in exploring human history. They have helped to conclusively establish that anatomically modern humans first appeared in Africa roughly 250,000-350,000 years before present and subsequently migrated to other parts of the world. The history of humans in Africa is complex and includes demographic events that influenced patterns of genetic variation across the continent. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021759DOI Listing
August 2018
1 Read

Single-Cell (Multi)omics Technologies.

Annu Rev Genomics Hum Genet 2018 08 4;19:15-41. Epub 2018 May 4.

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

Single-cell multiomics technologies typically measure multiple types of molecule from the same individual cell, enabling more profound biological insight than can be inferred by analyzing each molecular layer from separate cells. These single-cell multiomics technologies can reveal cellular heterogeneity at multiple molecular layers within a population of cells and reveal how this variation is coupled or uncoupled between the captured omic layers. The data sets generated by these techniques have the potential to enable a deeper understanding of the key biological processes and mechanisms driving cellular heterogeneity and how they are linked with normal development and aging as well as disease etiology. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-genom-0914
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http://dx.doi.org/10.1146/annurev-genom-091416-035324DOI Listing
August 2018
1 Read

Ancient Genomics of Modern Humans: The First Decade.

Annu Rev Genomics Hum Genet 2018 08 25;19:381-404. Epub 2018 Apr 25.

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19103, USA; email:

The first decade of ancient genomics has revolutionized the study of human prehistory and evolution. We review new insights based on prehistoric modern human genomes, including greatly increased resolution of the timing and structure of the out-of-Africa expansion, the diversification of present-day non-African populations, and the earliest expansions of those populations into Eurasia and America. Prehistoric genomes now document population transformations on every inhabited continent-in particular the effect of agricultural expansions in Africa, Europe, and Oceania-and record a history of natural selection that shapes present-day phenotypic diversity. 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-083117-021749DOI Listing
August 2018
25 Reads

Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease.

Annu Rev Genomics Hum Genet 2018 08 25;19:201-222. Epub 2018 Apr 25.

Cystic Fibrosis/Pulmonary Research and Treatment Center, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; email: ,

In many respects, genetic studies in cystic fibrosis (CF) serve as a paradigm for a human Mendelian genetic success story. From recognition of the condition as a heritable pathological entity to implementation of personalized treatments based on genetic findings, this multistep pathway of progress has focused on the genetic underpinnings of CF clinical disease. Along this path was the recognition that not all CFTR gene mutations produce the same disease and the recognition of the complex, multifactorial nature of CF genotype-phenotype relationships. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021329DOI Listing

Inferring Causal Relationships Between Risk Factors and Outcomes from Genome-Wide Association Study Data.

Annu Rev Genomics Hum Genet 2018 08 25;19:303-327. Epub 2018 Apr 25.

MRC Biostatistics Unit, University of Cambridge, Cambridge CB2 0SR, United Kingdom; email:

An observational correlation between a suspected risk factor and an outcome does not necessarily imply that interventions on levels of the risk factor will have a causal impact on the outcome (correlation is not causation). If genetic variants associated with the risk factor are also associated with the outcome, then this increases the plausibility that the risk factor is a causal determinant of the outcome. However, if the genetic variants in the analysis do not have a specific biological link to the risk factor, then causal claims can be spurious. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021731DOI Listing
August 2018
4 Reads

Drug-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Call for Optimum Patient Stratification and Theranostics via Pharmacogenomics.

Annu Rev Genomics Hum Genet 2018 08 13;19:329-353. Epub 2018 Apr 13.

South East Asian Pharmacogenomics Research Network (SEAPHARM).

The Global Genomic Medicine Collaborative, a multinational coalition of genomic and policy experts working to implement genomics in clinical care, considers pharmacogenomics to be among the first areas in genomic medicine that can provide guidance in routine clinical practice, by linking genetic variation and drug response. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe life-threatening reactions to medications with a high incidence worldwide. Genomic screening prior to drug administration is a key opportunity and potential paradigm for using genomic medicine to reduce morbidity and mortality and ultimately eliminate one of the most devastating adverse drug reactions. Read More

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http://dx.doi.org/10.1146/annurev-genom-083115-022324DOI Listing
August 2018
2 Reads

Using Full Genomic Information to Predict Disease: Breaking Down the Barriers Between Complex and Mendelian Diseases.

Annu Rev Genomics Hum Genet 2018 08 11;19:289-301. Epub 2018 Apr 11.

Charles Bronfman Institute for Personalized Medicine and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; email:

While sequence-based genetic tests have long been available for specific loci, especially for Mendelian disease, the rapidly falling costs of genome-wide genotyping arrays, whole-exome sequencing, and whole-genome sequencing are moving us toward a future where full genomic information might inform the prognosis and treatment of a variety of diseases, including complex disease. Similarly, the availability of large populations with full genomic information has enabled new insights about the etiology and genetic architecture of complex disease. Insights from the latest generation of genomic studies suggest that our categorization of diseases as complex may conceal a wide spectrum of genetic architectures and causal mechanisms that ranges from Mendelian forms of complex disease to complex regulatory structures underlying Mendelian disease. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021136DOI Listing

Sickle Cell Anemia and Its Phenotypes.

Annu Rev Genomics Hum Genet 2018 08 11;19:113-147. Epub 2018 Apr 11.

Sickle Cell Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1589, USA; email:

In the 100 years since sickle cell anemia (SCA) was first described in the medical literature, studies of its molecular and pathophysiological basis have been at the vanguard of scientific discovery. By contrast, the translation of such knowledge into treatments that improve the lives of those affected has been much too slow. Recent years, however, have seen major advances on several fronts. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021320DOI Listing
August 2018
3 Reads

From a Single Child to Uniform Newborn Screening: My Lucky Life in Pediatric Medical Genetics.

Authors:
R Rodney Howell

Annu Rev Genomics Hum Genet 2018 08 1;19:1-14. Epub 2018 Mar 1.

Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA; email:

Mike, a memorable young patient with untreated phenylketonuria, as well as others affected by genetic disorders that could be treated if diagnosed in infancy, launched my six-decade career. This autobiographical article reflects on my childhood, early research, and professional experiences in pediatric genetics. My laboratory research focused on inborn errors of metabolism, including the glycogen storage diseases. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021611DOI Listing
August 2018
2 Reads

The Genomic Commons.

Annu Rev Genomics Hum Genet 2018 08 25;19:429-453. Epub 2018 Jan 25.

Centre of Genomics and Policy and Department of Medicine, McGill University, Montreal, Quebec H3A 0G1, Canada; email:

Over its 30 or so years of existence, the genomic commons-the worldwide collection of publicly accessible repositories of human and nonhuman genomic data-has enjoyed remarkable, perhaps unprecedented, success. Thanks to the rapid public data release policies initiated by the Human Genome Project, free access to a vast array of scientific data is now the norm, not only in genomics, but in scientific disciplines of all descriptions. And far from being a monolithic creation of bureaucratic fiat, the genomic commons is an exemplar of polycentric, multistakeholder governance. Read More

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http://dx.doi.org/10.1146/annurev-genom-083117-021552DOI Listing
August 2018
1 Read

Cognitive Dysfunctions in Intellectual Disabilities: The Contributions of the Ras-MAPK and PI3K-AKT-mTOR Pathways.

Annu Rev Genomics Hum Genet 2017 08;18:115-142

Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.

The Ras-MAPK and PI3K-AKT-mTOR signaling cascades were originally identified as cancer regulatory pathways but have now been demonstrated to be critical for synaptic plasticity and behavior. Neurodevelopmental disorders arising from mutations in these pathways exhibit related neurological phenotypes, including cognitive dysfunction, autism, and intellectual disability. The downstream targets of these pathways include regulation of transcription and protein synthesis. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035332DOI Listing
August 2017
33 Reads

Recent Advancements in DNA Damage-Transcription Crosstalk and High-Resolution Mapping of DNA Breaks.

Annu Rev Genomics Hum Genet 2017 08;18:87-113

FIRC Institute of Molecular Oncology (IFOM), Milan 20139, Italy; email:

Until recently, DNA damage arising from physiological DNA metabolism was considered a detrimental by-product for cells. However, an increasing amount of evidence has shown that DNA damage could have a positive role in transcription activation. In particular, DNA damage has been detected in transcriptional elements following different stimuli. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035314DOI Listing
August 2017
3 Reads

The Genetic Diversity of the Americas.

Annu Rev Genomics Hum Genet 2017 08;18:277-296

Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, United Kingdom.

The history of the Americas involved the encounter of millions of Native Americans, Europeans, and Africans. A variable admixture of these three continental groups has taken place throughout the continent, influenced by demography and a range of social factors. This variable admixture has had a major influence on the genetic makeup of populations across the continent. Read More

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http://www.annualreviews.org/doi/10.1146/annurev-genom-08311
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http://dx.doi.org/10.1146/annurev-genom-083115-022331DOI Listing
August 2017
9 Reads

Application of Panel-Based Tests for Inherited Risk of Cancer.

Annu Rev Genomics Hum Genet 2017 08 15;18:201-227. Epub 2017 May 15.

Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; email:

Next-generation or massively parallel sequencing has transformed the landscape of genetic testing for cancer susceptibility. Panel-based genetic tests evaluate multiple genes simultaneously and rapidly. Because these tests are frequently offered in clinical settings, understanding their clinical validity and utility is critical. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035305DOI Listing
August 2017
5 Reads

Advances in Preimplantation Genetic Testing for Monogenic Disease and Aneuploidy.

Annu Rev Genomics Hum Genet 2017 08 12;18:189-200. Epub 2017 May 12.

Foundation for Embryonic Competence, Basking Ridge, New Jersey 07920.

Genetic testing of preimplantation embryos promises to prevent monogenic disease in children born to at-risk couples, the transfer of unbalanced embryos to patients carrying a balanced translocation, and the use of aneuploid embryos created during in vitro fertilization. Technologies have evolved from fluorescence in situ hybridization to next-generation-sequencing-based aneuploidy screening and allow for simultaneous testing of multiple genetic abnormalities in a single biopsy. The field has also shifted away from polar body or blastomere biopsy and toward trophectoderm biopsy as the new standard. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035508DOI Listing
August 2017
8 Reads

Tailoring Medulloblastoma Treatment Through Genomics: Making a Change, One Subgroup at a Time.

Annu Rev Genomics Hum Genet 2017 08 5;18:143-166. Epub 2017 May 5.

Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; email:

After more than a decade of genomic studies in medulloblastoma, the time has come to capitalize on the knowledge gained and use it to directly improve patient care. Although metastatic and relapsed disease remain poorly understood, much has changed in how we define medulloblastoma, and it has become evident that with conventional therapies, specific groups of patients are currently under- or overtreated. In this review, we summarize the latest insights into medulloblastoma biology, focusing on how genomics is affecting patient stratification, informing preclinical studies of targeted therapies, and shaping the new generation of clinical trials. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035434DOI Listing
August 2017
28 Reads

A Robust Framework for Microbial Archaeology.

Annu Rev Genomics Hum Genet 2017 08 26;18:321-356. Epub 2017 Apr 26.

Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Jena 07745, Germany; email:

Microbial archaeology is flourishing in the era of high-throughput sequencing, revealing the agents behind devastating historical plagues, identifying the cryptic movements of pathogens in prehistory, and reconstructing the ancestral microbiota of humans. Here, we introduce the fundamental concepts and theoretical framework of the discipline, then discuss applied methodologies for pathogen identification and microbiome characterization from archaeological samples. We give special attention to the process of identifying, validating, and authenticating ancient microbes using high-throughput DNA sequencing data. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581243PMC
August 2017
24 Reads

Precisely Where Are We Going? Charting the New Terrain of Precision Prevention.

Annu Rev Genomics Hum Genet 2017 08 24;18:369-387. Epub 2017 Apr 24.

Center for Bioethics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; email:

In addition to genetic data, precision medicine research gathers information about three factors that modulate gene expression: lifestyles, environments, and communities. The relevant research tools-epidemiology, environmental assessment, and socioeconomic analysis-are those of public health sciences rather than molecular biology. Because these methods are designed to support inferences and interventions addressing population health, the aspirations of this research are expanding from individualized treatment toward precision prevention in public health. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203331PMC
August 2017
14 Reads

On the Evolution of Lactase Persistence in Humans.

Annu Rev Genomics Hum Genet 2017 08 19;18:297-319. Epub 2017 Apr 19.

Laboratoire Éco-Anthropologie et Ethnobiologie, UMR 7206 CNRS - Muséum national d'Histoire naturelle - Univ Paris Diderot, Sorbonne Paris Cité, F-75016 Paris, France; email: ,

Lactase persistence-the ability of adults to digest the lactose in milk-varies widely in frequency across human populations. This trait represents an adaptation to the domestication of dairying animals and the subsequent consumption of their milk. Five variants are currently known to underlie this phenotype, which is monogenic in Eurasia but mostly polygenic in Africa. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035340DOI Listing
August 2017
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The Yin and Yang of Autism Genetics: How Rare De Novo and Common Variations Affect Liability.

Annu Rev Genomics Hum Genet 2017 08 19;18:167-187. Epub 2017 Apr 19.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; email:

The etiology of autism spectrum disorder (ASD) is complex, involving both genetic and environmental contributions to individual and population-level liability. Early researchers hypothesized that ASD arises from polygenic inheritance, but later results, such as the identification of mutations in certain genes that are responsible for syndromes associated with ASD, led others to propose that de novo mutations of major effect would account for most cases. This yin and yang of monogenic causes and polygenic inheritance continues to this day. Read More

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http://dx.doi.org/10.1146/annurev-genom-083115-022647DOI Listing
August 2017
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Participatory Genomic Research: Ethical Issues from the Bottom Up to the Top Down.

Annu Rev Genomics Hum Genet 2017 08 19;18:357-367. Epub 2017 Apr 19.

Ethics Center, Division of General and Community Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; email:

Participatory approaches to genomic research manifest along a continuum from bottom-up citizen-science initiatives designed to liberate scientific inquiry from the constraints of traditional research institutional contexts and professional practices to top-down investigator-initiated studies designed to expose the public to scientific research processes and build its support and enthusiasm for genomic research. With foundations as varied as open science, crowdsourcing, patient advocacy, social media, the digitization of health, and the neoliberalization of academic research, a range of ethical frameworks inform the modes of participatory genomic research. Using illustrations from citizen genomic science, patient advocacy, and investigator-led and government-initiated genomic research efforts, we argue that as participatory genomic research pushes the conventional research boundaries toward a more democratizing ethos, it challenges scientific practices and the ethical conduct of genomic research both within and outside of the traditional sites of biomedical innovation. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035230DOI Listing
August 2017
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Recent Advances in Mitochondrial Disease.

Annu Rev Genomics Hum Genet 2017 08 17;18:257-275. Epub 2017 Apr 17.

Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom; email:

Mitochondrial disease is a challenging area of genetics because two distinct genomes can contribute to disease pathogenesis. It is also challenging clinically because of the myriad of different symptoms and, until recently, a lack of a genetic diagnosis in many patients. The last five years has brought remarkable progress in this area. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035426DOI Listing
August 2017
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Sharing Data to Build a Medical Information Commons: From Bermuda to the Global Alliance.

Annu Rev Genomics Hum Genet 2017 08 17;18:389-415. Epub 2017 Apr 17.

Program in History of Science, Department of History, Princeton University, Princeton, New Jersey 08544.

The Human Genome Project modeled its open science ethos on nematode biology, most famously through daily release of DNA sequence data based on the 1996 Bermuda Principles. That open science philosophy persists, but daily, unfettered release of data has had to adapt to constraints occasioned by the use of data from individual people, broader use of data not only by scientists but also by clinicians and individuals, the global reach of genomic applications and diverse national privacy and research ethics laws, and the rising prominence of a diverse commercial genomics sector. The Global Alliance for Genomics and Health was established to enable the data sharing that is essential for making meaning of genomic variation. Read More

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http://dx.doi.org/10.1146/annurev-genom-083115-022515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634517PMC
August 2017
1 Read

Gene and Variant Annotation for Mendelian Disorders in the Era of Advanced Sequencing Technologies.

Annu Rev Genomics Hum Genet 2017 08 17;18:229-256. Epub 2017 Apr 17.

Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322; email:

Comprehensive annotations of genetic and noncoding regions and corresponding accurate variant classification for Mendelian diseases are the next big challenge in the new genomic era of personalized medicine. Progress in the development of faster and more accurate pipelines for genome annotation and variant classification will lead to the discovery of more novel disease associations and candidate therapeutic targets. This ultimately will facilitate better patient recruitment in clinical trials. Read More

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http://www.annualreviews.org/doi/10.1146/annurev-genom-08311
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http://dx.doi.org/10.1146/annurev-genom-083115-022545DOI Listing
August 2017
2 Reads

Gene Regulatory Elements, Major Drivers of Human Disease.

Annu Rev Genomics Hum Genet 2017 08 7;18:45-63. Epub 2017 Apr 7.

Department of Bioengineering and Therapeutic Sciences and Institute for Human Genetics, University of California, San Francisco, California 94158; email:

Gene expression changes, the driving forces for cellular diversity in multicellular organisms, are regulated by a diverse set of gene regulatory elements that direct transcription in specific cells. Mutations in these elements, ranging from chromosomal aberrations to single-nucleotide polymorphisms, are a major cause of human disease. However, we currently have a very limited understanding of how regulatory element genotypes lead to specific phenotypes. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035537DOI Listing
August 2017
9 Reads

The Microbiome and Human Biology.

Annu Rev Genomics Hum Genet 2017 08 20;18:65-86. Epub 2017 Mar 20.

Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, Massachusetts 02543.

Over the past few years, microbiome research has dramatically reshaped our understanding of human biology. New insights range from an enhanced understanding of how microbes mediate digestion and disease processes (e.g. Read More

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http://dx.doi.org/10.1146/annurev-genom-083115-022438DOI Listing
August 2017
15 Reads

The Clinic Is My Laboratory: Life as a Clinical Geneticist.

Authors:
Judith G Hall

Annu Rev Genomics Hum Genet 2017 08 6;18:1-29. Epub 2017 Mar 6.

Department of Medical Genetics and Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver V6H 3N1, Canada; email:

Clinical genetics is the application of advances in genetics and medicine to real human families. It involves diagnosis, care, and counseling concerning options available to affected individuals and their family members. Advances in medicine and genetics have led to dramatic changes in the scope and responsibilities of clinical genetics. Read More

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http://dx.doi.org/10.1146/annurev-genom-091416-035213DOI Listing
August 2017
1 Read