Hereditary genetics : current research最新文献

{"title":"Epigenomic Indicators of Age in African Americans","authors":"Jennifer A. Smith, Alicia L. Zagel, Yan V. Sun, D. Dolinoy, L. Bielak, P. Peyser, S. Turner, T. Mosley, S. Kardia","doi":"10.4172/2161-1041.1000137","DOIUrl":"https://doi.org/10.4172/2161-1041.1000137","url":null,"abstract":"Age is a well-established risk factor for chronic diseases. However, the cellular and molecular changes associated with aging processes that are related to chronic disease initiation and progression are not well-understood. Thus, there is an increased need to identify new markers of cellular and molecular changes that occur during aging processes. In this study, we use genome-wide DNA methylation from 26,428 CpG sites in 13,877 genes to investigate the relationship between age and epigenetic variation in the peripheral blood cells of 972 African American adults from the Genetic Epidemiology Network of Arteriopathy (GENOA) study (mean age=66.3 years, range=39–95). Age was significantly associated with 7,601 (28.8%) CpG sites after Bonferroni correction for α=0.05 (p<1.89×10−6). Due to the extraordinarily strong associations between age and many of the CpG sites (>7,000 sites with p-values ranging from 10−6 to 10−43), we investigated how well the DNA methylation markers predict age. We found that 2,095 (7.9%) CpG sites were significant predictors of age after Bonferroni correction. The top five principal components of the 2,095 age-associated CpG sites accounted for 69.3% of the variability in these CpG sites, and they explained 26.8% of the variation in age. The associations between methylation markers and adult age are so ubiquitous and strong that we hypothesize that DNA methylation patterns may be an important measure of cellular aging processes. Given the highly correlated nature of the age-associated epigenome (as evidenced by the principal components analysis), whole pathways may be regulated as a consequence of aging.","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79526608","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":"Current status in diagnosis and treatment of hereditary thrombotic thrombocytopenic purpura.","authors":"Hayley A Hanby,&nbsp;X Long Zheng","doi":"10.4172/2161-1041.1000e108","DOIUrl":"https://doi.org/10.4172/2161-1041.1000e108","url":null,"abstract":"","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204482/pdf/nihms607045.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32769816","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":"Antioxidants: The Missing Key to Improved Therapeutic Intervention in Smith-Lemli-Opitz Syndrome?","authors":"Steven J Fliesler","doi":"10.4172/2161-1041.1000119","DOIUrl":"https://doi.org/10.4172/2161-1041.1000119","url":null,"abstract":"<p><p>Smith-Lemli-Opitz Syndrome (SLOS) is a recessive hereditary disease caused by an enzymatic defect in the biosynthesis of cholesterol. To date, the therapeutic standard of care for this disease has been cholesterol supplementation therapy. However, the efficacy of this treatment is extremely variable and, in many if not most cases, is poor. Results of studies using animal models of SLOS have suggested that cholesterol deficiencyand/or the aberrant accumulation of the immediate precursor of cholesterol (7-dehydrocholesterol (7DHC)), per se, may not be the sole culprits in the pathobiology of this disease. Rather, cytotoxic oxysterol by-products derived specifically from 7DHC are thought to be additional, significant, causative players in the disease mechanism. Based in large measure upon such studies, a recent clinical trial, comparing the therapeutic efficacyof cholesterol supplementation alone vs. combined cholesterol-antioxidant supplementation in SLOS patients, has provided extremely encouraging results that tend to both validate the proposed role of oxysterols in the pathobiology of SLOS as well as indicate an improved treatment for this and related diseases.</p>","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"2 2","pages":"119"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32121216","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":"Triple Negative Breast Cancer - An Overview.","authors":"Kartik Aysola,&nbsp;Akshata Desai,&nbsp;Crystal Welch,&nbsp;Jingyao Xu,&nbsp;Yunlong Qin,&nbsp;Vaishali Reddy,&nbsp;Roland Matthews,&nbsp;Charlotte Owens,&nbsp;Joel Okoli,&nbsp;Derrick J Beech,&nbsp;Chandrika J Piyathilake,&nbsp;Shyam P Reddy,&nbsp;Veena N Rao","doi":"10.4172/2161-1041.S2-001","DOIUrl":"https://doi.org/10.4172/2161-1041.S2-001","url":null,"abstract":"<p><p>Triple Negative Breast Cancer (TNBC) is a heterogeneous disease that based on immunohistochemistry (IHC) is estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER2) negative. TNBC is typically observed in young AA women and Hispanic women who carry a mutation in the BRCA1 gene. TNBC is characterized by a distinct molecular profile, aggressive nature and lack of targeted therapies. The purpose of this article is to review the current and future novel signalling pathways as therapeutic approaches to TNBC. Recent Identification of a new BRCA1 trafficking pathway holds promise in the future for the development of targeted therapies for TNBC.</p>","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"2013 Suppl 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1041.S2-001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32722310","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":"ADAMTS13, TTP and Beyond.","authors":"X Long Zheng","doi":"10.4172/2161-1041.1000e104","DOIUrl":"https://doi.org/10.4172/2161-1041.1000e104","url":null,"abstract":"Copyright: © 2012 Zheng XL. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"2 1","pages":"e104"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32309815","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":"Implication of the Strand-Specific Imprinting and Segregation Model: Integrating <i>in utero</i> Hormone Exposure, Stem Cell and Lateral Asymmetry Hypotheses in Breast Cancer Aetiology.","authors":"Singh Harbinder,&nbsp;Carol A Lazzara,&nbsp;Amar Js Klar","doi":"10.4172/2161-1041.s2-005","DOIUrl":"https://doi.org/10.4172/2161-1041.s2-005","url":null,"abstract":"<p><p>Known genetic mutations and familial hereditary factors account for less than 20-25% of breast cancer cases in women, therefore, most instances have been classified as sporadic cases of unknown aetiologies. Single nucleotide polymorphisms (SNPs) were considered as breast cancer risk factors, but numerous studies have failed to support this assertion. Recent evidence correlates aberrant epigenetic mechanisms in the development and metastatic progression of breast cancer, yet there has been limited progress made to identify the primary aetiology underlying sporadic cases of breast cancer. This has led some researchers to consider alternative hypotheses including <i>in utero</i> exposure to deleterious chemical agents during early development, the immortal strand and the strand-specific imprinting and selective chromatid segregation hypotheses. Here, we integrate prominent alternate models to help guide future research on this very important topic concerning human health.</p>","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"2013 Suppl 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39471218","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":"Metformin- A Promising Agent for Chemoprevention in <i>BRCA1</i> Carriers.","authors":"Nagi B Kumar,&nbsp;Susan T Vadaparampil,&nbsp;Nupam Mahajan,&nbsp;Howard S Lilienfeld,&nbsp;Ji-Hyun Lee,&nbsp;Christine Laronga,&nbsp;Ardeshir Hakam,&nbsp;John J Hein,&nbsp;Kathleen M Egan,&nbsp;Banu Arun,&nbsp;Tuya Pal","doi":"10.4172/2161-1041.1000104","DOIUrl":"https://doi.org/10.4172/2161-1041.1000104","url":null,"abstract":"Women who carry germline mutations in the BRCA1 gene (BRCA1 carriers) have the highest individual lifetime risk for breast cancer (BCa) known [1-3], with 50% of carriers developing breast cancer by age 50. BRCA2 carriers also have a higher risk but relatively lower than BRCA1 carriers. Currently available options for both BRCA1 and BRCA2 carriers include high-risk surveillance, risk reducing mastectomy or chemoprevention with the ant-estrogens Tamoxifen (TAM) and Raloxifene. Chemoprevention has been controversial in that BRCA1 carriers tend to make estrogen receptor negative tumors. Selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene reduce the risk of estrogen receptor positive breast cancers. For example, results from the National Surgical Adjuvant Breast and Bowel Project (NSABP1) Tamoxifen chemoprevention study suggested that TAM is not effective in carriers of a BRCA1 mutation [4]. Regardless, there is conflicting evidence on this point and both TAM and Raloxifene are offered to BRCA1 carriers as well as BRCA2 carriers [5]. As a chemoprotective agent in the general population, Raloxifene shows a similar reduction in risk for invasive breast cancer to TAM, but not for in situ cancers, which comprise >20% of newly diagnosed cases; the incidence of noninvasive breast cancer is approximately 40% lower for women on TAM compared with Raloxifene [6,7]. Both TAM and Raloxifene are effective only against estrogen receptor-positive tumors [8], and Raloxifene is typically only prescribed in women who are postmenopausal and have decreased bone density [9]. Both drugs increase risk for serious side effects, including venous thrombosis and pulmonary embolism [10,11]. TAM is also associated with an increased risk for endometrial cancer and stroke [12-14]. Other side effects of both drugs include dyspareunia, cataracts, musculoskeletal complaints including leg cramps, weight gain, hot flashes, vaginal discharge, bone loss in premenopausal women and bladder control problems [15]. More recently, long-term administration of TAM was observed to cause hepatic tumors in rats, induced via a genotoxic mechanism [16]. Compounding the unfavorable side affect profile studies have determined that approximately 5 – 10% of the population carries a homozygous variant of the CYP2D6 gene that imparts low activity to convert TAM from its less active form to its active metabolite [17]. This research led the FDA to require a change in the labeling of Tamoxifen to include this information [18]. Concerns about the risk: benefit ratio have thus limited the use of TAM for prevention. Recent evidence suggests that only approximately 8.4% of BRCA carriers who have not undergone prophylactic mastectomy and are eligible to take Tamoxifen or Raloxifene [19], for risk reduction do so [20]. Certainly, there is an urgent need to identify other agents for breast cancer prevention in this high-risk group. In fact, data from our own Inherited Cancer Registry (ICAR","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33407553","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":"Epistatic Control of Mammary Cancer Susceptibility in Mice may Depend on the Dietary Environment.","authors":"Larry J Leamy, Ryan R Gordon, Daniel Pomp","doi":"10.4172/2161-1041.1000108","DOIUrl":"10.4172/2161-1041.1000108","url":null,"abstract":"<p><p>Recent studies have linked a high fat diet to the development of breast cancer, but any genetic basis for this association is poorly understood. We investigated this association with an epistatic analysis of seven cancer traits in a segregating population of mice with metastatic mammary cancer that were fed either a control or a high-fat diet. We used an interval mapping approach with single nucleotide polymorphisms to scan all 19 autosomes, and discovered a number of diet-independent epistatic interactions of quantitative trait loci (QTLs) affecting these traits. More importantly, we also discovered significant epistatic by diet interactions affecting some of the traits that suggested these epistatic effects varied depending on the dietary environment. An analysis of these interactions showed some were due to epistasis that occurred in mice fed only the control diet or only the high-fat diet whereas other interactions were generated by differential effects of epistasis in the two dietary environments. Some of the epistatic QTLs appeared to colocalize with cancer QTLs mapped in other mouse populations and with candidate genes identified from eQTLs previously mapped in this population, but others represented novel modifying loci affecting these cancer traits. It was concluded that these diet-dependent epistatic QTLs contribute to a genetic susceptibility of dietary effects on breast cancer, and their identification may eventually lead to a better understanding that will be needed for the design of more effective treatments for this disease.</p>","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"1 2","pages":"108"},"PeriodicalIF":0.0,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32146063","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":"Initiation of DNA Replication in the Human Genome.","authors":"Manuel S Valenzuela","doi":"10.4172/2161-1041.S1-003","DOIUrl":"10.4172/2161-1041.S1-003","url":null,"abstract":"<p><p>Replication of the human genome relies on the presence of thousands of origins distributed along each of the chromosomes. The activation of these origins occurs in a highly regulated manner to ensure that chromosomes are faithfully duplicated only once during each cell cycle. Failure in this regulation can lead to abnormal cell proliferation, or/and genomic instability, the hallmarks of cancer cells. The mechanisms determining how, when, and where origins are activated remains still a mystery. However recent technological advances have facilitated the study of DNA replication in a genome-wide scale, and have provided a wealth of information on several features of this process. Here we present an overview of the current progress on our understanding of the initiation step of DNA replication in human cells, and its relationship to abnormal cell proliferation.</p>","PeriodicalId":90176,"journal":{"name":"Hereditary genetics : current research","volume":"Suppl 1 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915928/pdf/nihms453194.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32101985","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}