AIMS Genetics最新文献

{"title":"Tissue interactions, cell signaling and transcriptional control in the cranial mesoderm during craniofacial development","authors":"Xiaochen Fan, D. Loebel, Heidi Bildsoe, Emilie E. Wilkie, J. Qin, Junwen Wang, P. Tam","doi":"10.3934/genet.2016.1.74","DOIUrl":"https://doi.org/10.3934/genet.2016.1.74","url":null,"abstract":"Abstract The cranial neural crest and the cranial mesoderm are the source of tissues from which the bone and cartilage of the skull, face and jaws are constructed. The development of the cranial mesoderm is not well studied, which is inconsistent with its importance in craniofacial morphogenesis as a source of precursor tissue of the chondrocranium, muscles, vasculature and connective tissues, mechanical support for tissue morphogenesis, and the signaling activity that mediate interactions with the cranial neural crest. Phenotypic analysis of conditional knockout mouse mutants, complemented by the transcriptome analysis of differentially enriched genes in the cranial mesoderm and cranial neural crest, have identified signaling pathways that may mediate cross-talk between the two tissues. In the cranial mesenchyme, Bmp4 is expressed in the mesoderm cells while its signaling activity could impact on both the mesoderm and the neural crest cells. In contrast, Fgf8 is predominantly expressed in the cranial neural crest cells and it influences skeletal development and myogenesis in the cranial mesoderm. WNT signaling, which emanates from the cranial neural crest cells, interacts with BMP and FGF signaling in monitoring the switch between tissue progenitor expansion and differentiation. The transcription factor Twist1, a critical molecular regulator of many aspects of craniofacial development, coordinates the activity of the above pathways in cranial mesoderm and cranial neural crest tissue compartments.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248857","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":"Congenital tracheal defects: embryonic development and animal models","authors":"Z. Sher, Karen J. Liu","doi":"10.3934/genet.2016.1.60","DOIUrl":"https://doi.org/10.3934/genet.2016.1.60","url":null,"abstract":"Abstract Tracheal anomalies are potentially catastrophic congenital defects. As a newborn begins to breathe, the trachea needs to maintain an appropriate balance of elasticity and rigidity. If the tracheal cartilages are disorganized or structurally weak, the airways can collapse, obstructing breathing. Cartilage rings that are too small or too rigid can also obstruct breathing. These anomalies are frequently associated with craniofacial syndromes, and, despite the importance, are poorly understood. In this review, we summarize the spectrum of pathological phenotypes of the trachea and correlate them with the molecular events uncovered in mouse models.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248823","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":"Aarskog-Scott syndrome: phenotypic and genetic heterogeneity","authors":"M. Jabalameli, I. Briceño, J. Martinez, R. Pengelly, S. Ennis, A. Collins","doi":"10.3934/genet.2016.1.49","DOIUrl":"https://doi.org/10.3934/genet.2016.1.49","url":null,"abstract":"Abstract Aarskog-Scott syndrome (AAS) is a rare developmental disorder which primarily affects males and has a relative prevalence of 1 in 25,000 in the general population. AAS patients usually present with developmental complications including short stature and facial, skeletal and urogenital anomalies. The spectrum of genotype-phenotype correlations in AAS is unclear and mutations of the FGD1 gene on the proximal short arm of chromosome X account for only 20% of the incidence of the disorder. Failure to identify pathogenic variants in patients referred for FGD1 screening suggests heterogeneity underlying pathophysiology of the condition. Furthermore, overlapping features of AAS with several other developmental disorders increase the complexity of diagnosis. Cytoskeletal signaling may be involved in the pathophysiology of AAS. The FGD1 protein family has a role in activation of CDC42 (Cell Division Control protein 42 homolog) which has a core function in remodeling of extracellular matrix and the transcriptional activation of many modulators of development. Therefore, mutations in components in the EGFR1 (Epidermal Growth Factor Receptor 1) signaling pathway, to which CDC42 belongs, may contribute to pathophysiology. Parallel sequencing strategies (so-called next generation sequencing or high throughput sequencing) enables simultaneous production of millions of sequencing reads that enormously facilitate cost-effective identification of cryptic mutations in heterogeneous monogenic disorders. Here we review the source of phenotypic and genetic heterogeneity in the context of AAS and discuss the applicability of next generation sequencing for identification of novel mutations underlying AAS.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248813","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":"Towards defining the Mechanisms of Alzheimer's disease based on a contextual analysis of molecular pathways","authors":"J. Richens, J. P. Bramble, H. Spencer, Fiona Cantlay, Molly Butler, P. O'shea","doi":"10.3934/genet.2016.1.25","DOIUrl":"https://doi.org/10.3934/genet.2016.1.25","url":null,"abstract":"Abstract Alzheimer's disease (AD) is posing an increasingly profound problem to society. Our genuine understanding of the pathogenesis of AD is inadequate and as a consequence, diagnostic and therapeutic strategies are currently insufficient. The understandable focus of many studies is the identification of molecules with high diagnostic utility however the opportunity to obtain a further understanding of the mechanistic origins of the disease from such putative biomarkers is often overlooked. This study examines the involvement of biomarkers in AD to shed light on potential mechanisms and pathways through which they are implicated in the pathology of this devastating neurodegenerative disorder. The computational tools required to analyse ever-growing datasets in the context of AD are also discussed.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248780","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":"Telomeres, species differences, and unusual telomeres in vertebrates: presenting challenges and opportunities to understanding telomere dynamics","authors":"Emory D. Ingles, J. Deakin","doi":"10.3934/genet.2016.1.1","DOIUrl":"https://doi.org/10.3934/genet.2016.1.1","url":null,"abstract":"Abstract There has been increasing interest in the use of telomeres as biomarkers of stress, cellular ageing and life-histories. However, the telomere landscape is a diverse feature, with noticeable differences between species, a fact which is highlighted by the unusual telomeres of various vertebrate organisms. We broadly review differences in telomere dynamics among vertebrates, and emphasize the need to understand more about telomere processes and trends across species. As part of these species differences, we review unusual telomeres in vertebrates. This includes mega-telomeres, which are present across a diverse set of organisms, but also focusing on the unusual telomeres traits of marsupials and monotremes, which have seen little to no prior discussion, yet uniquely stand out from other unusual telomere features discovered thus far. Due to the presence of at least two unique telomere features in the marsupial family Dasyuridae, as well as to the presence of physiological strategies semelparity and torpor, which have implications for telomere life-histories in these species, we suggest that this family has a very large potential to uncover novel information on telomere evolution and dynamics.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248770","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":"Genetic and flow anomalies in congenital heart disease.","authors":"Sandra Rugonyi","doi":"10.3934/genet.2016.3.157","DOIUrl":"10.3934/genet.2016.3.157","url":null,"abstract":"<p><p>Congenital heart defects are the most common malformations in humans, affecting approximately 1% of newborn babies. While genetic causes of congenital heart disease have been studied, only less than 20% of human cases are clearly linked to genetic anomalies. The cause for the majority of the cases remains unknown. Heart formation is a finely orchestrated developmental process and slight disruptions of it can lead to severe malformations. Dysregulation of developmental processes leading to heart malformations are caused by genetic anomalies but also environmental factors including blood flow. Intra-cardiac blood flow dynamics plays a significant role regulating heart development and perturbations of blood flow lead to congenital heart defects in animal models. Defects that result from hemodynamic alterations, however, recapitulate those observed in human babies, even those due to genetic anomalies and toxic teratogen exposure. Because important cardiac developmental events, such as valve formation and septation, occur under blood flow conditions while the heart is pumping, blood flow regulation of cardiac formation might be a critical factor determining cardiac phenotype. The contribution of flow to cardiac phenotype, however, is frequently ignored. More research is needed to determine how blood flow influences cardiac development and the extent to which flow may determine cardiac phenotype.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34974586","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":"Pros and cons of HaloPlex enrichment in cancer predisposition genetic diagnosis","authors":"Agnès Collet, J. Tarabeux, E. Girard, C. D. d’Enghien, L. Golmard, Vivien Deshaies, Alban Lermine, A. Laugé, V. Moncoutier, C. Lefol, F. Copigny, C. Dehainault, Henrique Tenreiro, C. Guy, Khadija Abidallah, C. Barbaroux, E. Rouleau, N. Servant, A. Pauw, D. Stoppa-Lyonnet, C. Houdayer","doi":"10.3934/genet.2015.4.263","DOIUrl":"https://doi.org/10.3934/genet.2015.4.263","url":null,"abstract":"Abstract Panel sequencing is a practical option in genetic diagnosis. Enrichment and library preparation steps are critical in the diagnostic setting. In order to test the value of HaloPlex technology in diagnosis, we designed a custom oncogenetic panel including 62 genes. The procedure was tested on a training set of 71 controls and then blindly validated on 48 consecutive hereditary breast/ovarian cancer (HBOC) patients tested negative for BRCA1/2 mutation. Libraries were sequenced on HiSeq2500 and data were analysed with our academic bioinformatics pipeline. Point mutations were detected using Varscan2, median size indels were detected using Pindel and large genomic rearrangements (LGR) were detected by DESeq. Proper coverage was obtained. However, highly variable read depth was observed within genes. Excluding pseudogene analysis, all point mutations were detected on the training set. All indels were also detected using Pindel. On the other hand, DESeq allowed LGR detection but with poor specificity, preventing its use in diagnostics. Mutations were detected in 8% of BRCA1/2-negative HBOC cases. HaloPlex technology appears to be an efficient and promising solution for gene panel diagnostics. Data analysis remains a major challenge and geneticists should enhance their bioinformatics knowledge in order to ensure good quality diagnostic results.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248695","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":"Rare genetic variants: making the connection with breast cancer susceptibility","authors":"T. Nguyen-Dumont, J. Stewart, I. Winship, M. Southey","doi":"10.3934/genet.2015.4.281","DOIUrl":"https://doi.org/10.3934/genet.2015.4.281","url":null,"abstract":"Abstract The practice of clinical genetics in the context of breast cancer predisposition has reached another critical point in its evolution. For the past two decades, genetic testing offered to women attending clinics has been limited to BRCA1 and BRCA2 unless other syndromic indicators have been evident (e.g. PTEN and TP53 for Cowden and Li-Fraumeni syndrome, respectively). Women (and their families) who are concerned about their personal and/or family history of breast and ovarian cancer have enthusiastically engaged with clinical genetics services, anticipating a genetic cause for their cancer predisposition will be identified and to receive clinical guidance for their risk management and treatment options. Genetic testing laboratories have demonstrated similar enthusiasm for transitioning from single gene to gene panel testing that now provide opportunities for the large number of women found not to carry mutations in BRCA1 and BRCA2, enabling them to undergo additional genetic testing. However, these panel tests have limited clinical utility until more is understood about the cancer risks (if any) associated with the genetic variation observed in the genes included on these panels. New data is urgently needed to improve the interpretation of the genetic variation data that is already reported from these panels and to inform the selection of genes included in gene panel tests in the future. To address this issue, large internationally coordinated research studies are required to provide the evidence-base from which clinical genetics for breast cancer susceptibility can be practiced in the era of gene panel testing and oncogenetic practice. Two significant steps associated with this process include i) validating the genes on these panels (and those likely to be added in the future) as bona fide1 breast cancer predisposition genes and ii) interpreting the variation, on a variant-by-variant basis in terms of their likely “pathogenicity”—a process commonly referred to as “variant classification” that will enable this new genetic information to be used at an individual level in clinical genetics services. Neither of these fundamental steps have been achieved for the majority of genes included on the panels. We are thus at a critical point for translational research in breast cancer clinical genetics—how can rare genetic variants be interpreted such that they can be used in clinical genetics services and oncogenetic practice to identify and to inform the management of families that carry these variants?","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248738","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":"Associations of CYP1A1 gene polymorphisms and risk of breast cancer in Indian women: a meta-analysis","authors":"N. Pabalan, Neetu Singh, E. Singian, C. Barbosa, B. Bianco, H. Jarjanazi","doi":"10.3934/genet.2015.4.250","DOIUrl":"https://doi.org/10.3934/genet.2015.4.250","url":null,"abstract":"Abstract Reported associations of CYP1A1 polymorphisms with breast cancer have been inconsistent. In this meta-analysis examining breast cancer associations of three CYP1A1 polymorphisms (M1, M2 and M4) among Indian women may yield information that may be of clinical and epidemiological use for this particular demography. We searched MEDLINE using PubMed and Embase for association studies. From seven published case-control studies, we estimated overall associations and applied subgroup analysis to explore differential effects. All three polymorphisms exhibited overall increased risk, significant in M1 (OR 1.61–1.65, p = 0.04) and M4 (OR 2.02–3.92, p = 0.02–0.04). Differential effects were observed only in the M1 polymorphism where M1 effects were significant in South Indians (OR 2.20–4.34, p < 0.0001) but not the North population, who were at reduced risk (OR 0.64–0.77, p = 0.03–0.55). These populations were not materially different in regard to M2 and M4 as did the women stratified by menopausal status. In this meta-analysis, M1 and M4 effects may render Indian women susceptible, but may be limited by heterogeneity of the studies. Differential effects of the M1 polymorphism in breast cancer render South Indians susceptible compared to those in the North.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248686","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":"The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer’s disease","authors":"S. Yoon, Yong-Ku Kim","doi":"10.3934/genet.2015.3.230","DOIUrl":"https://doi.org/10.3934/genet.2015.3.230","url":null,"abstract":"Abstract Alzheimer's disease is an important public concern with rising prevalence across the globe. While many therapeutic approaches for Alzheimer's disease have been developed, there are currently no validated disease-modifying treatments. Thus, in order to develop novel treatment strategies, there is a significant need to progress our understanding of the pathogenesis of Alzheimer's disease. Several large genome-wide association studies and whole genome and exome sequencing studies have identified novel genes associated with late-onset Alzheimer's disease. Interestingly, many of the genes are associated with inflammation and the immune system, including complement receptor 1, clusterin, CD33, EPH receptor A1, membrane-spanning 4-domains subfamily A, ATP-binding cassette sub-family A member 7, major histocompatibility complex class II, inositol polyphosphate-5-phosphatase, myocyte enhancer factor 2C, and triggering receptor expressed on myeloid cells 2. The pathogenetic contributions of immune reaction and neuroinflammation in Alzheimer's disease have been regarded largely as part of amyloid cascade hypothesis. The neurotoxic amyloid-β (Aβ) induces activation of immune cells, such as microglia, astrocytes, perivascular macrophages and lymphocytes and decreased capability of clearing Aβ by immune system and chronic inflammation caused by activated immune cells aggravate neuronal damage and eventually Alzheimer's disease. But the precise mechanism and hereditary impact on such process is largely unknown. The current findings in genetic studies suggest that the immunological mechanisms of Alzheimer's disease may extend beyond passive reaction of Aβ, including the development of Alzheimer's disease such as time of onset and rate of progression. In this article, we aimed to review the mechanisms of immune reaction and neuroinflammation in Alzheimer's disease, with an emphasis on the function of genes known to be associated with a risk of Alzheimer's disease in terms of neuroinflammation and immune function.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248675","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}