Advances in Genetics: Incorporating, Molecular Genetic Medicine: 33

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This article has been cited by other articles in PMC. Abstract Personalized medicine uses traditional, as well as emerging concepts of the genetic and environmental basis of disease to individualize prevention, diagnosis and treatment. Introduction Personalized medicine did not begin in the post-genome era. The relationship of genomics and personalized medicine There has long been interest in personalizing medicine. The scope of scientific challenges facing the use of personalized genomics in medicine The scientific foundation for personalized genomics draws on a range of disciplines including, among others, basic genetics, population genetics, genetic and clinical epidemiology, behavioral science, and emerging regulatory science.

Open in a separate window. Human disease susceptibility is the result of rare genetic variants of high penetrance as well as common genomic variants of low penetrance After more than a decade of debate between the Common Disease, Common Variant CDCV and Common Disease Rare Variant CDRV camps, it is now evident that both sides have won. The genomic model of human disease, like the multifactorial genetic model, will incorporate environmental as well as genetic modifiers The genetics era produced important insights into the interaction of genetic and environmental factors, for example the metabolism of carcinogens mediated by xenobiotic genes Shields and Harris , as well as the first models of pharmacogenetic variants of drug metabolism Katz and Bhathena The individual response to probabilistic genetic information varies and depends on context There is variation both within families and between individuals regarding the processing of probabilistic risk information, and ability to act on it.

Genetic or genomic markers with proven analytic and clinical validity and a strong biological rationale may not meet evidence-based standards of clinical utility Over the past two decades clinical investigators have established an evidence base for the utility of genetic tests in a variety of medical contexts. Concluding comments There is little debate that the extraordinary progress in genome science over the past decade, coupled with the declining cost of sequencing technologies, has brought the promise of personalized medicine closer than ever.

References Agency for Healthcare Research and Quality Testing for cytochrome P polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors SSRIs , structured abstract. January , Rockville, MD. J Clin Oncol Clinical assessment incorporating a personal genome.

Personalized medicine: new genomics, old lessons

Effect of direct-to-consumer genomewide profiling to assess disease risk. N Engl J Med. Discovering genotypes underlying human phenotypes: Cellular functions of the BRCA tumour-suppressor proteins. Psychological impact of genetic counseling for familial cancer: J Natl Cancer Inst. Disclosure of individual genetic data to research participants: Pediatric acute lymphoblastic leukemia.

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Curr Opin Genet Dev 20 3: Has the revolution arrived? Personalized medicine and genomics: Bio IT World Nov 12, Evidence based medicine meets genomic medicine. Sunday Times Sept 7, Orphanet J Rare Dis. Hereditary cancer predisposition syndromes. PLoS Genet 6 Charting a course for genomic medicine from base pairs to bedside. A model process for the evaluating data on emerging genetic tests. Oxford University Press; The path to personalized medicine. A systematic review of perceived risks, psychological and behavioral impacts of genetic testing.

Inheritance of epigenetic aberrations constitutional epimutations in cancer susceptibility. Curr Protoc Hum Genet Chap 9: Genetics and genomics in practice: The continuum of translation research in genomic medicine: Gene-expression-based prognostic assays for breast cancer. Nat Rev Clin Oncol.

Estimation of the warfarin dose with clinical and pharmacogenetic data. Genetic testing in Li-Fraumeni syndrome: Clinical implications of the cancer genome. Genomewide association studies and assessment of the risk of disease. New Engl J Med. Waiting for the revolution. Genomics and the continuum of cancer care.

Personalized medicine: new genomics, old lessons

A policy model to evaluate the benefits, risks and costs of warfarin pharmacogenomic testing. Advances in understanding cancer genomes through second-generation sequencing.

Genetic testing in the long QT syndrome: An agenda for personalized medicine. A summary of the 25th international papillomavirus conference Genomic profiles for disease risk: Breast cancer single-nucleotide polymorphisms: Preimplantation genetic diagnosis for cancer syndromes: Challenges in the clinical application of whole-genome sequencing.

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Common genetic variation and human disease. Chicago Tribune, September 26, Occult hepatitis C virus infection: The 8q24 cancer risk variant rs shows long-range interaction with MYC in colorectal cancer. The origins of theoretical population genetics. The University of Chicago Press; Management of an inherited predisposition to breast cancer.

The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. A network view of disease and compound screening. Nat Rev Drug Discov. Common vs rare allele hypothesis for complex diseases. Curr Opin Genet Dev. Strong association of de novo copy number mutations with autism. Cancer risk and low-penetrance susceptibility genes in gene—environment interactions.

Association of cytochrome P 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Genome-wide association studies of cancer predisposition. Hematol Oncol Clin N Am. Multiplex PCR to diagnose bloodstream infections in patients admitted from the emergency department with sepsis.

Food and Drug Administration Table of pharmacogenomic biomarkers in drug labels. A de novo paradigm for mental retardation. Genomic Law Report Website. Accessed 27 Jan Wade N A decade later, genetic map yields few new cures. Advances in ADHD pharmacogenetics can potentially identify novel, targeted treatments for different subgroups of patients; the use of such patientspecific treatments could substantially improve the efficacy and safety of ADHD treatment.

Overall, the findings have been inconsistent and disappointing. Clearly there needs to be a re-focusing of effort to move this field forward. The old methods are not generating much useful information so we should be actively trying new methods. Studies that integrate genetic findings with imaging assessments of brain structure and function [] are needed to identify the changes in the brain that link genetic to behavioral changes.

Longitudinal studies are needed to identify the genetic and environment factors that predict spontaneous recovery prior to adulthood versus a lifetime course of illness. Finally, the research culture and funding mechanisms that promote the conduct of large numbers of small-sample, underpowered studies — a problem that is particularly evident in China — needs to change.

Large collaborative studies between centers that rigorously ensure standardization of procedures are essential to achieving the sample sizes needed to identify uncommon, but etiologically important, genetic variants. She is interested in research related to the genetics of ADHD. The authors declare no conflict of interest. National Center for Biotechnology Information , U. Journal List Shanghai Arch Psychiatry v. Received Jun 16; Accepted Jul To view a copy of this license, visit http: This article has been cited by other articles in PMC.

Candidate gene studies 2. Dopaminergic system DA system The dopaminergic theory, proposed by Levy, [11] suggests that DA deficits in specific brain regions, such as cortical areas and the striatum, results in ADHD symptoms. Noradrenergic system NE system Although stimulant medications appear to act primarily by regulating dopamine levels in the brain, noradrenergic and serotonergic functions may also be affected by ADHD medications. Serotonergic system 5-HT system Serotonin has been shown to influence a variety of behaviors relevant to ADHD, including impulsivity, aggression, dis-inhibition, and attention, thus it is thought to play a causal role in ADHD.

Enzyme system Molecular studies have provided compelling evidence for the association of ADHD with genes that encode enzymes involved in the metabolism of catecholamine and serotonin. Dopamine beta-hydroxylase DBH DBH catalyzes the primary enzyme responsible for conversion of DA to NE, and is found in sympathetic terminals, adrenal glands, and in the prefrontal cortex.

Dopamine decarboxylase DDC Dopa decarboxylase catalyses the formation of functional dopamine through decarboxylation of a precursor tyrosine derivative and it participates in the synthesis of trace amine compounds that are believed to act as modulators of central neurotransmission. Genes of synaptic vesicle proteins Psychiatric and neurological diseases are often characterized by the occurrence of aberrant synaptic formation, function, and plasticity, or by malformed dendritic spines.

Endophenotype Endophenotype is a heritable trait associated with a disease that is measurable and, thus, it serves as an intermediate marker between genotype and phenotype. Pharmacogenomic studies Genetics has the potential to provide an invaluable contribution to the pharmacological management of ADHD.

Open in a separate window. Footnotes Conflict of interest: Biederman J, Faraone SV. The worldwide prevalence of ADHD: An epidemiological investigation of minimal brain dysfunction in six elementary schools in Beijing. J Child Psychol Psychiatry. What have we learnt about the causes of ADHD? Candidate gene studies of ADHD: Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet. The dopamine transporter gene is associated with attention deficit hyperactivity disorder in a Taiwanese sample.

Family-based and case-control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder. Kobe J Med Sci. No association between VNTR polymorphisms of dopamine transporter gene and attention deficit hyperactivity disorder in Chinese children. Association study of promoter polymorphisms at the dopamine transporter gene in Attention Deficit Hyperactivity Disorder. Association between the dopamine transporter gene and the inattentive subtype of attention deficit hyperactivity disorder in Taiwan.

Prog Neuropsychopharmacol Biol Psychiatry. Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder.

What is a gene?

Faraone SV, Mick E. Molecular genetics of attention deficit hyperactivity disorder. Psychiatr Clin North Am. Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder ADHD Hum Mol Genet. Association of dopamine D4 receptor DRD4 polymorphisms with attention deficit hyperactivity disorder in Indian population.

Cheuk DK, Wong V. Meta-analysis of association between a catechol-O-methyltransferase gene polymorphism and attention deficit hyperactivity disorder. A casecontrol association study of the polymorphism at the promoter region of the DRD4 gene in Korean boys with attention deficithyperactivity disorder: Exon 3 polymorphisms of dopamine D4 receptor DRD4 gene and attention deficit hyperactivity disorder in Chinese children. Buy and read on Free Kindle Apps. Kindle Edition File Size: Academic Press; 1 edition 14 November Sold by: Customer reviews There are no customer reviews yet.

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