Current genetic medicine reports最新文献

{"title":"Management and Screening in Neurofibromatosis Types 1 and 2","authors":"A. Shaw","doi":"10.1007/s40142-019-00165-8","DOIUrl":"https://doi.org/10.1007/s40142-019-00165-8","url":null,"abstract":"","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 1","pages":"92-101"},"PeriodicalIF":2.1,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40142-019-00165-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49310302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherited Endocrine Neoplasia— A Comprehensive Review from Gland to Gene","authors":"Alexander T. Deng, L. Izatt","doi":"10.1007/s40142-019-00166-7","DOIUrl":"https://doi.org/10.1007/s40142-019-00166-7","url":null,"abstract":"","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 1","pages":"102-115"},"PeriodicalIF":2.1,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40142-019-00166-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43408773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Cancer Susceptibility—Towards Individualised Risk Prediction","authors":"Inge M M Lakeman, M. Schmidt, C. Asperen, P. Devilee","doi":"10.1007/s40142-019-00168-5","DOIUrl":"https://doi.org/10.1007/s40142-019-00168-5","url":null,"abstract":"","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 1","pages":"124-135"},"PeriodicalIF":2.1,"publicationDate":"2019-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40142-019-00168-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46643943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits and Challenges of Rare Genetic Variation in Alzheimer's Disease.","authors":"Detelina Grozeva, Salha Saad, Georgina E Menzies, Rebecca Sims","doi":"10.1007/s40142-019-0161-5","DOIUrl":"10.1007/s40142-019-0161-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>It is well established that sporadic Alzheimer's disease (AD) is polygenic with common and rare genetic variation alongside environmental factors contributing to disease. Here, we review our current understanding of the genetic architecture of disease, paying specific attention to rare susceptibility variants, and explore some of the limitations in rare variant detection and analysis.</p><p><strong>Recent findings: </strong>Rare variation has been shown to robustly associate with disease. These include potentially damaging and loss of function mutations that are easily modelled in silico, in vitro and in vivo, and represent potentially druggable targets. A number of risk genes, including <i>TREM2</i>, <i>SORL1</i> and <i>ABCA7</i> show multiple independent associations suggesting that they may influence disease via multiple mechanisms. With transcriptional regulation, inflammatory response and modification of protein production suggested to be of primary importance.</p><p><strong>Summary: </strong>We are at the beginning of our journey of rare variant detection in AD. Whole exome sequencing has been the predominant technology of choice. While fruitful, this has introduced a number of challenges with regard to data integration. Ultimately the future of disease-associated rare variant identification lies in whole genome sequencing projects that will allow the testing of the full range of genomic variation.</p>","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 1","pages":"53-62"},"PeriodicalIF":1.4,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44286682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Variants in Alzheimer's Disease.","authors":"Shea J Andrews, Brian Fulton-Howard, Alison Goate","doi":"10.1007/s40142-019-0156-2","DOIUrl":"10.1007/s40142-019-0156-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>Over the last decade over 40 loci have been associated with risk of Alzheimer's disease (AD). However, most studies have either focused on identifying risk loci or performing unbiased screens without a focus on protective variation in AD. Here, we provide a review of known protective variants in AD and their putative mechanisms of action. Additionally, we recommend strategies for finding new protective variants.</p><p><strong>Recent findings: </strong>Recent Genome-Wide Association Studies have identified both common and rare protective variants associated with AD. These include variants in or near <i>APP, APOE, PLCG2, MS4A, MAPT-KANSL1, RAB10, ABCA1, CCL11, SORL1, NOCT, SCL24A4-RIN3</i>, <i>CASS4, EPHA1, SPPL2A</i>, and <i>NFIC</i>.</p><p><strong>Summary: </strong>There are very few protective variants with functional evidence and a derived allele with a frequency below 20%. Additional fine mapping and multi-omic studies are needed to further validate and characterize known variants as well as specialized genome-wide scans to identify novel variants.</p>","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 1","pages":"1-12"},"PeriodicalIF":2.1,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40142-019-0156-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9953358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in the Genetic Architecture of Alzheimer's Disease.","authors":"Logan Dumitrescu, Elizabeth Rose Mayeda, Kavya Sharman, Annah M Moore, Timothy J Hohman","doi":"10.1007/s40142-019-0157-1","DOIUrl":"10.1007/s40142-019-0157-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>Summarize sex-specific contributors to the genetic architecture of Alzheimer's disease (AD).</p><p><strong>Recent findings: </strong>There are sex differences in the effects of Apolipoprotein E (<i>APOE</i>), genes along the <i>APOE</i> pathway, and genes along the neurotrophic signaling pathway in predicting AD. Reported sex differences are largely driven by stronger associations among females. Evidence also suggests that genetic predictors of amyloidosis are largely shared across sexes, while sex-specific genetic effects emerge downstream of amyloidosis and drive the clinical manifestation of AD.</p><p><strong>Summary: </strong>There is a lack of comprehensive assessments of sex differences in genome-wide analyses of AD and a need for more systematic reporting a sex-stratified genetic effects. The emerging emphasis on sex as a biological variable provides an opportunity for transdisciplinary collaborations aimed at addressing major analytical challenges that have hampered advancements in the field. Ultimately, sex-specific genetic association studies represent a logical first step towards precision medicine.</p>","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 1","pages":"13-21"},"PeriodicalIF":1.4,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662731/pdf/nihms-1519266.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41221831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Genetics of Frontotemporal Dementia","authors":"Daniel W. Sirkis, Ethan G. Geier, L. Bonham, C. Karch, J. Yokoyama","doi":"10.1007/s40142-019-0160-6","DOIUrl":"https://doi.org/10.1007/s40142-019-0160-6","url":null,"abstract":"","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 1","pages":"41-52"},"PeriodicalIF":2.1,"publicationDate":"2019-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40142-019-0160-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44404821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic Risk Scores in Neurodegenerative Diseases: a Review","authors":"L. Ibañez, F. Farias, U. Dube, K. Mihindukulasuriya, O. Harari","doi":"10.1007/s40142-019-0158-0","DOIUrl":"https://doi.org/10.1007/s40142-019-0158-0","url":null,"abstract":"","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 1","pages":"22-29"},"PeriodicalIF":2.1,"publicationDate":"2019-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40142-019-0158-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48689577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Integration of Genomics into Cancer Screening Programmes: Challenges and Opportunities.","authors":"Sarah Briggs, Ingrid Slade","doi":"10.1007/s40142-019-00162-x","DOIUrl":"10.1007/s40142-019-00162-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>As the costs of genomic testing have fallen, and our understanding of genetic susceptibility to cancers has grown, there has been increasing interest in incorporating testing for cancer susceptibility genes, and polygenic risk estimates, into population cancer screening. A growing body of evidence suggests that this would be both clinically and cost-effective. In this article, we aim to explore the frameworks used to evaluate screening programmes, evaluate whether population screening for cancer susceptibility can be assessed using these standards, and consider additional issues and outcomes of importance in this context.</p><p><strong>Recent findings: </strong>There are tensions between traditional approaches of genetic testing (utilising tests with high sensitivity and specificity) and the principles of population screening (in which the screening test typically has low specificity), as well as the frameworks used to evaluate the two. Despite the existence of many screening guidelines, including consensus papers, these often do not align fully with broader considerations of genetic test evaluation. Population screening for genetic risk in cancer shifts the focus from diagnostics to prognostication and has wider implications for personal and familial health than existing screening programmes. In addition, understanding of the prevalence and penetrance of cancer susceptibility genes, required by many screening guidelines, may only be obtainable through population-level testing; prospective multi-disciplinary research alongside implementation will be essential.</p><p><strong>Summary: </strong>Appropriate evaluation of genetic screening for cancer risk will require modification of existing screening frameworks to incorporate additional complexity of outcomes and population values. As evidence supporting population screening for cancer susceptibility mounts, development of an appropriate evaluative framework, and expansion of public dialogue will be key to informing policy.</p>","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 2","pages":"63-74"},"PeriodicalIF":2.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37694570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consent and Autonomy in the Genomics Era.","authors":"Rachel Horton,&nbsp;Anneke Lucassen","doi":"10.1007/s40142-019-00164-9","DOIUrl":"10.1007/s40142-019-00164-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>Genomic tests offer increased opportunity for diagnosis, but their outputs are often uncertain and complex; results may need to be revised and/or may not be relevant until some future time. We discuss the challenges that this presents for consent and autonomy.</p><p><strong>Recent findings: </strong>Popular discourse around genomic testing tends to be strongly deterministic and optimistic, yet many findings from genomic tests are uncertain or unclear. Clinical conversations need to anticipate and potentially challenge unrealistic expectations of what a genomic test can deliver in order to enhance autonomy and ensure that consent to genomic testing is valid.</p><p><strong>Summary: </strong>We conclude that 'fully informed' consent is often not possible in the context of genomic testing, but that an open-ended approach is appropriate. We consider that such broad consent can only work if located within systems or organisations that are trustworthy and that have measures in place to ensure that such open-ended agreements are not abused. We suggest that a relational concept of autonomy has benefits in encouraging focus on the networks and relationships that allow decision making to flourish.</p>","PeriodicalId":72731,"journal":{"name":"Current genetic medicine reports","volume":"7 2","pages":"85-91"},"PeriodicalIF":2.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40142-019-00164-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37397368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}