Abstract:
:Following the "finished," euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges.
journal_name
Annu Rev Medjournal_title
Annual review of medicineauthors
Gonzaga-Jauregui C,Lupski JR,Gibbs RAdoi
10.1146/annurev-med-051010-162644subject
Has Abstractpub_date
2012-01-01 00:00:00pages
35-61eissn
0066-4219issn
1545-326Xjournal_volume
63pub_type
杂志文章,评审abstract::Ductal carcinoma in situ of the breast is a heterogeneous group of lesions with diverse malignant potential. It is the most rapidly growing subgroup in the breast cancer family; it is projected that more than 39,000 new cases will be diagnosed in the United States during 1999. Most new cases are nonpalpable and are di...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.51.1.17
更新日期:2000-01-01 00:00:00
abstract::Leukocyte adhesion deficiency (LAD) is a recently recognized autosomal-recessive trait characterized by recurrent bacterial infections, impaired pus formation and wound healing, and abnormalities in a wide spectrum of adherence-dependent functions of granulocytes, monocytes, and lymphoid cells. Features of this diseas...
journal_title:Annual review of medicine
pub_type: 杂志文章
doi:10.1146/annurev.me.38.020187.001135
更新日期:1987-01-01 00:00:00
abstract::Acquired immunodeficiency syndrome indicates opportunistic infection or unusual malignancy associated with a marked deficiency of cell mediated immunity in the absence of any other cause of the immune defect. This review examines epidemiology, virology, and immunology associated with this disorder. The syndrome appear...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.36.020185.002553
更新日期:1985-01-01 00:00:00
abstract::Acute myocardial infarction is caused by coronary thrombosis on an ulcerated atheroma. We now believe that the predominant cause of this intimal disruption is the rupture of the atheroma through the intimal surface, caused by enzymes released by activated macrophages. The subsequent clinical course following atheroma ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.000343
更新日期:1991-01-01 00:00:00
abstract::Cystic diseases of the kidney are common, often progressive disorders. The best of several alternative hypotheses to explain their development cites tubular dilation and compression of adjacent tissue. The initiating event may involve focal proliferation of epithelial cells and a consequent increase in the resistance ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.39.020188.001153
更新日期:1988-01-01 00:00:00
abstract::CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 antibodies of varying formulations have been evaluated in the clinic ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-062518-045435
更新日期:2020-01-27 00:00:00
abstract::Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by fibrofatty replacement of the ventricular myocardium, a high risk of ventricular arrhythmias, and progressive ventricular dysfunction. The clinical course is highly variable, and optimal approaches to management remai...
journal_title:Annual review of medicine
pub_type: 杂志文章,meta分析
doi:10.1146/annurev-med-041217-010932
更新日期:2019-01-27 00:00:00
abstract::Monoclonal antibodies of defined specificity can be produced using hybridoma technology. New attempts are being made to explore the potential of antibody therapy for cancer. Preliminary studies show that problems such as antigenic modulation, circulating free antigen, effector cell shortage, and host anti-mouse immuno...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.34.020183.000543
更新日期:1983-01-01 00:00:00
abstract::The overexpression and aberrant function of members of the erbB family of receptors, particularly erbB1 (also known as epidermal growth factor receptor), and its ligands in many human cancers have provided a rationale for targeting this signaling network with novel approaches. erbB1 is a selective target for inhibitin...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.55.091902.104433
更新日期:2004-01-01 00:00:00
abstract::IgG subclasses represent distinct immunoglobulin types, each defined by unique primary structures of the constant region of the heavy-chain molecule, and each with characteristic biological and functional properties. New methods and reagents to measure serum concentrations have contributed to the study of the ontogeny...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.38.020187.001545
更新日期:1987-01-01 00:00:00
abstract::Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder manifested by immune-mediated thrombocytopenia. The diagnosis remains one of exclusion, after other thrombocytopenic disorders are ruled out based on history, physical examination, and laboratory evaluation. The goal of treatment is to raise th...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.56.082103.104644
更新日期:2005-01-01 00:00:00
abstract::Overdoses of tricyclic antidepressants (TCAs) leave no doubt that TCA drugs at high concentrations have serious cardiac effects. It has been assumed that, to a lesser extent, these effects will occur at usual therapeutic concentration. Recent prospective, plasma-level-controlled studies have improved our understanding...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.35.020184.002443
更新日期:1984-01-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a multistep process involving the interaction of viral envelope proteins with cell surface receptors. Binding to CD4 is followed by engagement of specific chemokine receptors (CCR5 or CXCR4), triggering molecular rearrangements in the envelope tran...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.58.080105.102908
更新日期:2007-01-01 00:00:00
abstract::Cardiac late potentials are observed by using a high-resolution, computer-processed ECG that can detect very low-level signals not seen with standard ECG techniques. Numerous clinical studies have demonstrated that patients with low-level signals after the QRS complexes (late potentials) are at much higher risk of ven...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.43.020192.001105
更新日期:1992-01-01 00:00:00
abstract::The development of an HIV vaccine is proving to be an unprecedented challenge. The difficulty in creating this vaccine arises from the enormous genetic variation of the virus and the unusual importance of cytotoxic T lymphocytes (CTL) in controlling its spread. Whereas traditional vaccine strategies are unlikely to co...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.54.101601.152349
更新日期:2005-01-01 00:00:00
abstract::The International HapMap Project produced a genome-wide database of human genetic variation for use in genetic association studies of common diseases. The initial output of these studies has been overwhelming, with over 150 risk loci identified in studies of more than 60 common diseases and traits. These associations ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.60.061907.093117
更新日期:2009-01-01 00:00:00
abstract::Atrial flutter is a macroreentrant tachyarrhythmia most often contained within the right atrium. Typical atrial flutter is defined on an electrocardiogram by the classic "sawtooth" pattern of flutter waves with negative polarity in leads II, III, and aVF. In contrast to atrial fibrillation, which is sustained by multi...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.49.1.77
更新日期:1998-01-01 00:00:00
abstract::New discoveries are expanding our knowledge of mechanisms involved in amyotrophic lateral sclerosis (ALS) pathogenesis. Some recent advances in our understanding of motoneuron death in familial ALS (fALS) and sporadic ALS (sALS) are reviewed, with emphasis on molecular similarities that may further unite these phenoty...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.46.1.133
更新日期:1995-01-01 00:00:00
abstract::Syncope is a common clinical problem comprising the sudden loss of both consciousness and postural tone, with a subsequent spontaneous and relatively prompt recovery. Often it is difficult to differentiate a true syncopal spell from other conditions, such as seizure disorders, or from some simple accidents. Even more ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.43.020192.001435
更新日期:1992-01-01 00:00:00
abstract::Caffeine is the most widely consumed stimulant drug in the world. This chapter reviews the human pharmacology of caffeine; the evidence for its role in causing human disease, including addiction; and its potential usefulness as a therapeutic agent. ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.41.020190.001425
更新日期:1990-01-01 00:00:00
abstract::Physiologic thrombolysis is efficient, while pathologic aberrations in the fibrinolytic system may result in either thrombotic or hemorrhagic disease. This review considers the molecular interactions involved in fibrinolysis, discusses the normal control mechanisms that provide for localized activation without systemi...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.37.020186.001155
更新日期:1986-01-01 00:00:00
abstract::Cardiac resynchronization therapy (CRT) is well established as a treatment for patients with moderate to severe heart failure on optimal medical therapy. Early studies demonstrated improved functional capacity and evidence of reverse remodeling; more recently, CRT has been associated with a survival benefit in advance...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.57.051804.122251
更新日期:2007-01-01 00:00:00
abstract::Both genetic and environmental factors contribute to the etiology of non-insulin-dependent diabetes. The genetic component is heterogeneous and in some patients is probably complex, involving multiple genes. Specific genetic defects have been identified for rate monogenic forms of NIDDM: maturity-onset diabetes of the...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.47.1.509
更新日期:1996-01-01 00:00:00
abstract::Our understanding of the role of the immune system in modulating glomerular injury continues to evolve. The participation of antibody, complement, and neutrophils alone cannot completely explain many aspects of the pathways of experimental and human glomerulonephritis. The elements of the immune system that mediate ce...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.000325
更新日期:1991-01-01 00:00:00
abstract::The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. In addition, the endothelium is a source of growth inhibitors and promoters of vascular smooth muscle...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.44.020193.002143
更新日期:1993-01-01 00:00:00
abstract::Infantile autism probably has many etiologies. Several specific genetic disorders appear to be associated with the syndrome much more often than would be expected by chance, but these account for only a minority of cases. In the majority of cases, where etiology is still unknown, genetic factors probably also play a r...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.36.020185.002215
更新日期:1985-01-01 00:00:00
abstract::Epidermolysis bullosa is a group of genetically determined diseases characterized by abnormal fragility of the skin and mucosa. In this chapter, we review current thinking about classification, pathogenesis, and molecular genetics, and we discuss management guidelines. ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.44.020193.001201
更新日期:1993-01-01 00:00:00
abstract::Eccrine sweat is produced by millions of miniscule glands buried in the skin. Eccrine sweating from the general body surface is an extremely important function in human thermoregulation; disturbances either in the control of sweating activity or in the glands themselves can result in problems ranging from minor social...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.34.020183.002241
更新日期:1983-01-01 00:00:00
abstract::Invasive electrophysiologic studies are used to guide drug and non-pharmacologic therapy, including surgery, in patients with ventricular tachycardia. We discuss the indications, methods, and results of electrophysiologic studies in these patients. Both catheter and intraoperative studies are described. This approach ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.37.020186.000245
更新日期:1986-01-01 00:00:00
abstract::It is now well recognized that the atherosclerotic plaques responsible for thrombus formation are not necessarily those that impinge most on the lumen of the vessel. Nevertheless, clinical investigations for atherosclerosis still focus on quantifying the degree of stenosis caused by plaques. Many of the features assoc...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-041709-133809
更新日期:2011-01-01 00:00:00