Pub Date : 2016-11-11DOI: 10.3934/genet.2016.4.239
N. Masood, Saman Khan, S. Luqman, Shakil Ahmed
Abstract Mad2 deletion strain of Schizosaccharomyces pombe was found to be sensitive to thymoquinone, a signature molecule present in Nigella sativa in a dose-dependent manner. Mad2 protein is an indispensable part of mitotic spindle checkpoint complex and is required for the cell cycle arrest in response to the spindle defects. Although the expression of α tubulin was not affected in thymoquinone treated cells, but the expression of β-tubulin was reduced. Further, the absence of microtubule in thymoquinone treated cells suggests its involvement in tubulin polymerization. Molecular docking studies revealed that thymoquinone specifically binds to β-tubulin near the Taxotere binding site of Tub1 (Tubulin α-β dimer). These studies additionally showed that thymoquinone interacts with the residues present in chain B, which is an inherent part of Mad2 protein of mitotic checkpoint complex (MCC). We concluded that the thymoquinone disrupts the microtubule polymerization that leads to the requirement of spindle checkpoint protein for the cell survival.
{"title":"Thymoquinone disrupts the microtubule dynamics in fission yeast Schizosaccharomyces pombe","authors":"N. Masood, Saman Khan, S. Luqman, Shakil Ahmed","doi":"10.3934/genet.2016.4.239","DOIUrl":"https://doi.org/10.3934/genet.2016.4.239","url":null,"abstract":"Abstract Mad2 deletion strain of Schizosaccharomyces pombe was found to be sensitive to thymoquinone, a signature molecule present in Nigella sativa in a dose-dependent manner. Mad2 protein is an indispensable part of mitotic spindle checkpoint complex and is required for the cell cycle arrest in response to the spindle defects. Although the expression of α tubulin was not affected in thymoquinone treated cells, but the expression of β-tubulin was reduced. Further, the absence of microtubule in thymoquinone treated cells suggests its involvement in tubulin polymerization. Molecular docking studies revealed that thymoquinone specifically binds to β-tubulin near the Taxotere binding site of Tub1 (Tubulin α-β dimer). These studies additionally showed that thymoquinone interacts with the residues present in chain B, which is an inherent part of Mad2 protein of mitotic checkpoint complex (MCC). We concluded that the thymoquinone disrupts the microtubule polymerization that leads to the requirement of spindle checkpoint protein for the cell survival.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248710","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}
Pub Date : 2016-11-08DOI: 10.3934/genet.2016.4.212
M. Hashemi, F. Bizhani, H. Danesh, B. Narouie, M. Sotoudeh, M. Radfar, M. Ramezani, G. Bahari, M. Taheri, S. Ghavami
Abstract MicroRNAs (miRNAs) participate in diverse biological pathways and may act as oncogenes or tumor suppressors. The single nucleotide polymorphisms (SNPs) in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608 rs4919510 C > G variant on bladder cancer risk. This case-control study conducted on 233 bladder cancer patients and 252 healthy subjects. Genotyping of miR-608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings showed that CG as well as CG + GG genotypes significantly increased the risk of bladder cancer (OR = 1.94, 95% CI = 1.28–2.94, p = 0.002, and OR = 1.90, 95% CI = 1.26–2.86, p = 0.002, respectively) compared to CC genotype. The G allele significantly increased the risk of bladder cancer compared to C allele (OR = 1.69, 95% CI = 1.17–2.45, p = 0.005). Our findings proposed that miR-608 polymorphism might be associated with increased risk of bladder cancer in a sample of Iranian population. Further large-scale studies with different ethnicities are needed to verify our findings.
MicroRNAs (miRNAs)参与多种生物学途径，可能作为致癌基因或肿瘤抑制因子。mirna中的单核苷酸多态性(snp)可能改变靶基因上的mirna结合位点，并影响mirna的表达。本研究旨在评估miR-608 rs4919510 C > G变异对膀胱癌风险的影响。本研究对233例膀胱癌患者和252名健康受试者进行了病例对照研究。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对miR-608 rs4919510进行基因分型。我们的研究结果显示，与CC基因型相比，CG和CG + GG基因型显著增加膀胱癌的风险(OR = 1.94, 95% CI = 1.28-2.94, p = 0.002; OR = 1.90, 95% CI = 1.26-2.86, p = 0.002)。与C等位基因相比，G等位基因显著增加膀胱癌的风险(OR = 1.69, 95% CI = 1.17-2.45, p = 0.005)。我们的研究结果表明，miR-608多态性可能与伊朗人群样本中膀胱癌风险增加有关。需要对不同种族进行进一步的大规模研究来验证我们的发现。
{"title":"MiR-608 rs4919510 C > G polymorphism increased the risk of bladder cancer in an Iranian population","authors":"M. Hashemi, F. Bizhani, H. Danesh, B. Narouie, M. Sotoudeh, M. Radfar, M. Ramezani, G. Bahari, M. Taheri, S. Ghavami","doi":"10.3934/genet.2016.4.212","DOIUrl":"https://doi.org/10.3934/genet.2016.4.212","url":null,"abstract":"Abstract\u0000 MicroRNAs (miRNAs) participate in diverse biological pathways and may act as oncogenes or tumor suppressors. The single nucleotide polymorphisms (SNPs) in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608 rs4919510 C > G variant on bladder cancer risk. This case-control study conducted on 233 bladder cancer patients and 252 healthy subjects. Genotyping of miR-608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings showed that CG as well as CG + GG genotypes significantly increased the risk of bladder cancer (OR = 1.94, 95% CI = 1.28–2.94, p = 0.002, and OR = 1.90, 95% CI = 1.26–2.86, p = 0.002, respectively) compared to CC genotype. The G allele significantly increased the risk of bladder cancer compared to C allele (OR = 1.69, 95% CI = 1.17–2.45, p = 0.005). Our findings proposed that miR-608 polymorphism might be associated with increased risk of bladder cancer in a sample of Iranian population. Further large-scale studies with different ethnicities are needed to verify our findings.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248659","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}
Pub Date : 2016-11-07DOI: 10.3934/genet.2016.4.219
H. Mozdarani, S. Mozdarani
Abstract Male infertility is caused by many factors including genetics. Although part of genetic damages are inherited and could be traced in blood leukocytes, but those de novo alterations induced in spermatogenesis are not part of diagnostic work up. De novo alterations might be the cause of many idiopathic conditions of male infertility. The aim of this study was to evaluate DNA damage, sex chromosomal aneuploidy and DAZ microdeletion in sperms of subfertile males in comparison with normal healthy individuals. Whole blood and semen samples were obtained from 75 subfertile and 45 normal men. Semen samples from karyotypically normal subfertile and normal individuals were used for DNA fragmentation, sex chromosome aneuploidy and DAZ microdeletion analysis. Sperm DNA damage was assessed by alkaline comet assay, chromosome aneuploidy and DAZ microdeletion was assessed using a combined primed in situ labeling and fluorescent in situ hybridization (PRINS-FISH) method. A significantly high percentage of DNA fragmentation was observed in subfertile patients compared to control. Similar observation was observed for sex chromosome aneuploidy and DAZ microdeletion (p < 0.01). A relatively small interindividual difference was seen in all three assays performed. However DAZ microdeletion was observed as mosaic form in Y bearing sperms. Results indicate that subfertile males experience higher genome instability in spermatogenesis expressed as DNA damage and consequently sperm chromosomal 220 AIMS Genetics Volume 3, Issue 4, 219-238. aneuploidy or microdeletions. Occurrence of de novo genetic alterations caused by environmental chemico-physical genotoxic agents during spermatogenesis might be one of the causes of idiopathic male infertility.
{"title":"De novo cytogenetic alterations in spermatozoa of subfertile males might be due to genome instability associated with idiopathic male infertility: Experimental evidences and Review of the literature","authors":"H. Mozdarani, S. Mozdarani","doi":"10.3934/genet.2016.4.219","DOIUrl":"https://doi.org/10.3934/genet.2016.4.219","url":null,"abstract":"Abstract\u0000 Male infertility is caused by many factors including genetics. Although part of genetic damages are inherited and could be traced in blood leukocytes, but those de novo alterations induced in spermatogenesis are not part of diagnostic work up. De novo alterations might be the cause of many idiopathic conditions of male infertility. The aim of this study was to evaluate DNA damage, sex chromosomal aneuploidy and DAZ microdeletion in sperms of subfertile males in comparison with normal healthy individuals. Whole blood and semen samples were obtained from 75 subfertile and 45 normal men. Semen samples from karyotypically normal subfertile and normal individuals were used for DNA fragmentation, sex chromosome aneuploidy and DAZ microdeletion analysis. Sperm DNA damage was assessed by alkaline comet assay, chromosome aneuploidy and DAZ microdeletion was assessed using a combined primed in situ labeling and fluorescent in situ hybridization (PRINS-FISH) method. A significantly high percentage of DNA fragmentation was observed in subfertile patients compared to control. Similar observation was observed for sex chromosome aneuploidy and DAZ microdeletion (p < 0.01). A relatively small interindividual difference was seen in all three assays performed. However DAZ microdeletion was observed as mosaic form in Y bearing sperms. Results indicate that subfertile males experience higher genome instability in spermatogenesis expressed as DNA damage and consequently sperm chromosomal 220 AIMS Genetics Volume 3, Issue 4, 219-238. aneuploidy or microdeletions. Occurrence of de novo genetic alterations caused by environmental chemico-physical genotoxic agents during spermatogenesis might be one of the causes of idiopathic male infertility.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248700","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}
Pub Date : 2016-09-27DOI: 10.3934/genet.2016.4.205
C. Apra, C. Collet, É. Arnaud, F. Rocco
Abstract Mutations in Fibroblast Growth Factor Receptor II (FGFR2) have been identified in patients with Crouzon and Pfeiffer syndrome, among which rare mutations of the intracellular tyrosine kinase domain. Correlating subtle phenotypes with each rare mutation is still in progress. In Necker-Enfants Malades Hospital, we identified three patients harboring three different pathogenic variants of the same amino acid residue Asn-549 located in this domain: in addition to a very typical crouzonoid appearance, they all developed clinically relevant hydrocephalus, which is an inconstant feature of Crouzon and Pfeiffer syndrome. Overall, FGFR2 tyrosine kinase domain mutations account for 5/67 (7.4%) cases in our hospital. We describe a novel mutation, p.Asn549Ser, and new cases of p.Asn549His and p.Asn549Thr mutations, each reported once before. Our three cases of Asn-549 mutations, alongside with rare previously reported cases, show that these patients are at higher risk of hydrocephalus. Clinical and imaging follow-up, with possible early surgery, may help prevent secondary intellectual disability.
{"title":"Changes in FGFR2 amino-acid residue Asn549 lead to Crouzon and Pfeiffer syndrome with hydrocephalus","authors":"C. Apra, C. Collet, É. Arnaud, F. Rocco","doi":"10.3934/genet.2016.4.205","DOIUrl":"https://doi.org/10.3934/genet.2016.4.205","url":null,"abstract":"Abstract Mutations in Fibroblast Growth Factor Receptor II (FGFR2) have been identified in patients with Crouzon and Pfeiffer syndrome, among which rare mutations of the intracellular tyrosine kinase domain. Correlating subtle phenotypes with each rare mutation is still in progress. In Necker-Enfants Malades Hospital, we identified three patients harboring three different pathogenic variants of the same amino acid residue Asn-549 located in this domain: in addition to a very typical crouzonoid appearance, they all developed clinically relevant hydrocephalus, which is an inconstant feature of Crouzon and Pfeiffer syndrome. Overall, FGFR2 tyrosine kinase domain mutations account for 5/67 (7.4%) cases in our hospital. We describe a novel mutation, p.Asn549Ser, and new cases of p.Asn549His and p.Asn549Thr mutations, each reported once before. Our three cases of Asn-549 mutations, alongside with rare previously reported cases, show that these patients are at higher risk of hydrocephalus. Clinical and imaging follow-up, with possible early surgery, may help prevent secondary intellectual disability.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248648","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}
Pub Date : 2016-09-25DOI: 10.3934/genet.2016.4.196
Cecilia Rodríguez, M. Cassini, G. Delgado, M. Ramírez, D. Centrón
Abstract Class 1 and 2 integrons are considered the paradigm of multidrug resistant (MDR) integrons. Although class 1 integrons have been found statistically associated to Enterobacteriaceae MDR isolates, this type of study has not been conducted for class 2 integrons. Escherichia coli and 3 species that were found that harbored more than 20% of class 2 integrons in clinical isolates, were selected to determine the role of intI2 as MDR marker. A total of 234 MDR/191 susceptible non-epidemiologically related isolates were analyzed. Seventy-four intI2 genes were found by PCR and sequencing. An intI2 relationship with MDR phenotypes in Acinetobacter baumannii and Enterobacter cloacae was found. No statistical association was identified with MDR E. coli and Helicobacter pylori isolates. In other words, the likelihood of finding intI2 is the same in susceptible and in MDR E. coli and H. pylori strains, suggesting a particular affinity between the mobile element Tn7 and some species. The use of intI2 as MDR marker was species-dependent, with fluctuating epidemiology at geographical and temporal gradients. The use of intI2 as MDR marker is advisable in A. baumannii, a species that can reach high frequencies of this genetic element.
{"title":"Analysis of class 2 integrons as a marker for multidrug resistance among Gram negative bacilli","authors":"Cecilia Rodríguez, M. Cassini, G. Delgado, M. Ramírez, D. Centrón","doi":"10.3934/genet.2016.4.196","DOIUrl":"https://doi.org/10.3934/genet.2016.4.196","url":null,"abstract":"Abstract Class 1 and 2 integrons are considered the paradigm of multidrug resistant (MDR) integrons. Although class 1 integrons have been found statistically associated to Enterobacteriaceae MDR isolates, this type of study has not been conducted for class 2 integrons. Escherichia coli and 3 species that were found that harbored more than 20% of class 2 integrons in clinical isolates, were selected to determine the role of intI2 as MDR marker. A total of 234 MDR/191 susceptible non-epidemiologically related isolates were analyzed. Seventy-four intI2 genes were found by PCR and sequencing. An intI2 relationship with MDR phenotypes in Acinetobacter baumannii and Enterobacter cloacae was found. No statistical association was identified with MDR E. coli and Helicobacter pylori isolates. In other words, the likelihood of finding intI2 is the same in susceptible and in MDR E. coli and H. pylori strains, suggesting a particular affinity between the mobile element Tn7 and some species. The use of intI2 as MDR marker was species-dependent, with fluctuating epidemiology at geographical and temporal gradients. The use of intI2 as MDR marker is advisable in A. baumannii, a species that can reach high frequencies of this genetic element.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70249097","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}
Pub Date : 2016-08-31DOI: 10.3934/genet.2016.3.167
K. Khalid
Abstract Type 1 diabetes mellitus (T1DM) is a T cell mediated autoimmune disease. Vitamin D was found to suppress the incidence of diabetes when bind to its receptor (VDR), probably by suppressing T cell activations. Thus the VDR gene polymorphism may have an impact on pathophysiology of this disease. Since there was no consistent association between VDR polymorphisms and the risk of T1DM, this study aimed to investigate a VDR gene polymorphism in Sudanese children with T1DM. We examined the VDR gene Bsm1 (rs1544410), Apa1 (rs7975232), and Taq1 (rs731236) single nucleotide polymorphisms in 174 children with T1DM, and 56 children as control, and the association of these polymorphisms with the diabetic control. Among study patients, the majority (85.63%) of diabetic patients reported metabolically poor controlled (HbA1c > 8%). As compared with the control, patients with T1DM presented more commonly with Bsm1 B allele (p = 0.001; OR 0.283; 95% CI 0.131–0.609) and Taq1 T allele (p = 0.05; OR 2.429; 95% CI 1.073–5.496). Apa1 A allele was less common in patients with T1DM without statistical difference (p = 0.862; OR 1.085; 95% CI 0.546–2.156). Our study suggests that, Bsm1 and Taq1 polymorphisms of the VDR gene associated with the prevalence of T1DM.
1型糖尿病(T1DM)是一种T细胞介导的自身免疫性疾病。研究发现，当维生素D与其受体(VDR)结合时，可能通过抑制T细胞激活来抑制糖尿病的发病率。因此，VDR基因多态性可能对本病的病理生理有影响。由于VDR多态性与T1DM风险之间没有一致的关联，本研究旨在调查苏丹T1DM儿童的VDR基因多态性。我们检测了174例T1DM患儿和56例对照患儿的VDR基因Bsm1 (rs1544410)、Apa1 (rs7975232)和Taq1 (rs731236)单核苷酸多态性，以及这些多态性与糖尿病对照的关系。在研究患者中，大多数(85.63%)糖尿病患者报告代谢控制不良(HbA1c bb0 8%)。与对照组相比，T1DM患者更常见的是bsm1b等位基因(p = 0.001;或0.283;95% CI 0.131-0.609)和Taq1 T等位基因(p = 0.05;或2.429;95% ci 1.073-5.496)。Apa1 A等位基因在T1DM患者中较少见，差异无统计学意义(p = 0.862;或1.085;95% ci 0.546-2.156)。我们的研究表明，VDR基因的Bsm1和Taq1多态性与T1DM的患病率有关。
{"title":"Vitamin D receptor gene polymorphisms in Sudanese children with type 1 diabetes","authors":"K. Khalid","doi":"10.3934/genet.2016.3.167","DOIUrl":"https://doi.org/10.3934/genet.2016.3.167","url":null,"abstract":"Abstract Type 1 diabetes mellitus (T1DM) is a T cell mediated autoimmune disease. Vitamin D was found to suppress the incidence of diabetes when bind to its receptor (VDR), probably by suppressing T cell activations. Thus the VDR gene polymorphism may have an impact on pathophysiology of this disease. Since there was no consistent association between VDR polymorphisms and the risk of T1DM, this study aimed to investigate a VDR gene polymorphism in Sudanese children with T1DM. We examined the VDR gene Bsm1 (rs1544410), Apa1 (rs7975232), and Taq1 (rs731236) single nucleotide polymorphisms in 174 children with T1DM, and 56 children as control, and the association of these polymorphisms with the diabetic control. Among study patients, the majority (85.63%) of diabetic patients reported metabolically poor controlled (HbA1c > 8%). As compared with the control, patients with T1DM presented more commonly with Bsm1 B allele (p = 0.001; OR 0.283; 95% CI 0.131–0.609) and Taq1 T allele (p = 0.05; OR 2.429; 95% CI 1.073–5.496). Apa1 A allele was less common in patients with T1DM without statistical difference (p = 0.862; OR 1.085; 95% CI 0.546–2.156). Our study suggests that, Bsm1 and Taq1 polymorphisms of the VDR gene associated with the prevalence of T1DM.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70249024","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}
Pub Date : 2016-08-23DOI: 10.3934/genet.2016.3.177
P. Scriven
Abstract A decision model was constructed to compare genetic testing and not testing, for the transfer of all suitable embryos, one at a time, from a cycle with up to ten embryos, until a first live birth was achieved or there were no more embryos available (a full cycle). Two strategies were investigated: (i) a fresh transfer with subsequent serial warmed cryopreserved embryo replacement, and (ii) freeze-all prior to serial embryo replacement. Sensitivity analyses were performed to assess the effect of embryo warming survival and diagnostic accuracy on cumulative rates. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio for a live birth event, and a clinical miscarriage avoided. Reproductive outcome probabilities were obtained from published prospective non-selection studies, and costs from websites and publications. Given 100% embryo warming survival and no false abnormal genetic test results, the live birth rate for a full cycle was the same with and without testing for both transfer strategies. Compared to not testing, it was theoretically possible for testing to be favoured for live birth only for the fresh and frozen transfer strategy, where more than one embryo was available, and dependent on the efficiency of warming survival and the positive predictive value of the test; however, this was unlikely to be cost-effective from a society perspective without a substantial reduction in genetic testing costs. For both transfer strategies, when more than one embryo was available, testing was more likely to achieve a live birth event following the first attempt with fewer attempts required overall. Testing was likely to be effective to avoid a clinical miscarriage but also to be expensive from a society perspective compared to the cost of dilation and curettage.
{"title":"Towards a better understanding of preimplantation genetic screening and cumulative reproductive outcome: transfer strategy, diagnostic accuracy and cost-effectiveness","authors":"P. Scriven","doi":"10.3934/genet.2016.3.177","DOIUrl":"https://doi.org/10.3934/genet.2016.3.177","url":null,"abstract":"Abstract A decision model was constructed to compare genetic testing and not testing, for the transfer of all suitable embryos, one at a time, from a cycle with up to ten embryos, until a first live birth was achieved or there were no more embryos available (a full cycle). Two strategies were investigated: (i) a fresh transfer with subsequent serial warmed cryopreserved embryo replacement, and (ii) freeze-all prior to serial embryo replacement. Sensitivity analyses were performed to assess the effect of embryo warming survival and diagnostic accuracy on cumulative rates. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio for a live birth event, and a clinical miscarriage avoided. Reproductive outcome probabilities were obtained from published prospective non-selection studies, and costs from websites and publications. Given 100% embryo warming survival and no false abnormal genetic test results, the live birth rate for a full cycle was the same with and without testing for both transfer strategies. Compared to not testing, it was theoretically possible for testing to be favoured for live birth only for the fresh and frozen transfer strategy, where more than one embryo was available, and dependent on the efficiency of warming survival and the positive predictive value of the test; however, this was unlikely to be cost-effective from a society perspective without a substantial reduction in genetic testing costs. For both transfer strategies, when more than one embryo was available, testing was more likely to achieve a live birth event following the first attempt with fewer attempts required overall. Testing was likely to be effective to avoid a clinical miscarriage but also to be expensive from a society perspective compared to the cost of dilation and curettage.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70249084","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}
Pub Date : 2016-07-11DOI: 10.3934/genet.2016.2.146
Jada Benn Torres
Abstract Within genetic anthropology, mitochondrial DNA (mtDNA) has garnered a prominent if not enduring place within the anthropological toolkit. MtDNA has provided new and innovative perspectives on the emergence and dispersal of our species, interactions with extinct human species, and illuminated relationships between human groups. In this paper, I provide a brief overview of the major findings ascertained from mtDNA about human origins, human dispersal across the globe, interactions with other hominin species, and the more recent uses of mtDNA in direct to consumer ancestry tests. Relative to nuclear DNA, mtDNA is a small section of the genome and due to its inheritance pattern provides a limited resolution of population history and an individual's genetic ancestry. Consequently, some scholars dismiss mtDNA as insignificant due to the limited inferences that may be made using the locus. Regardless, mtDNA provides some useful insights to understanding how social, cultural, and environmental factors have shaped patterns of genetic variability. Furthermore, with regard to the experiences of historically marginalized groups, in particular those of African descent throughout the Americas, mtDNA has the potential to fill gaps in knowledge that would otherwise remain unknown. Within anthropological sciences, the value of this locus for understanding human experience is maximized when contextualized with complementary lines of evidence.
{"title":"A history of you, me, and humanity: mitochondrial DNA in anthropological research","authors":"Jada Benn Torres","doi":"10.3934/genet.2016.2.146","DOIUrl":"https://doi.org/10.3934/genet.2016.2.146","url":null,"abstract":"Abstract Within genetic anthropology, mitochondrial DNA (mtDNA) has garnered a prominent if not enduring place within the anthropological toolkit. MtDNA has provided new and innovative perspectives on the emergence and dispersal of our species, interactions with extinct human species, and illuminated relationships between human groups. In this paper, I provide a brief overview of the major findings ascertained from mtDNA about human origins, human dispersal across the globe, interactions with other hominin species, and the more recent uses of mtDNA in direct to consumer ancestry tests. Relative to nuclear DNA, mtDNA is a small section of the genome and due to its inheritance pattern provides a limited resolution of population history and an individual's genetic ancestry. Consequently, some scholars dismiss mtDNA as insignificant due to the limited inferences that may be made using the locus. Regardless, mtDNA provides some useful insights to understanding how social, cultural, and environmental factors have shaped patterns of genetic variability. Furthermore, with regard to the experiences of historically marginalized groups, in particular those of African descent throughout the Americas, mtDNA has the potential to fill gaps in knowledge that would otherwise remain unknown. Within anthropological sciences, the value of this locus for understanding human experience is maximized when contextualized with complementary lines of evidence.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248956","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}
Pub Date : 2016-07-07DOI: 10.3934/genet.2016.2.130
Liliana Osório, F. Long, Zhongjun Zhou
Abstract The mammary gland is the distinct feature that gives the name to the class of mammals and distinguishes them from other animals. Functionally, the mammary gland is a secretory organ which main role is to produce milk to nourish the offspring. Organogenesis of the mammary gland starts during embryogenesis but occurs mainly after birth at puberty under the influence of hormonal cues. Throughout the adult life as well as during pregnancy, the mammary gland shows a remarkable regenerative ability, thus constituting an excellent model for studying stem cell biology. Although the mammary gland consists of a relatively simple epithelial structure with a luminal and a basal cell layers, these are indeed composed by distinct subsets of mammary epithelial cells. Flow cytometry and transplantation assay have identified several subpopulations of stem and/or progenitor cells in the mammary gland. Yet, physiological and developmental relevant information can only be obtained when investigating the stem cell hierarchy in the intact mammary gland. Genetic lineage tracing studies have offered unprecedented levels of information regarding the organization of the stem cell compartment and possible role of resident stem and/or progenitor cells at different stages of the mammary gland organogenesis. These studies, although creating a passionate debate, highlight the existence of heterogeneous stem cell compartment, where bipotent as well as unipotent mammary stem cells seems to co-exist. Genetic lineage tracing experiments provide relevant information on stem cells that are key for understanding both normal development as well as associated pathologies in human. It holds the promise of providing new insights into the cell-of-origin and heterogeneity of breast tumorigenesis.
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C. S. Fonteles, R. Finnell, T. George, R. Harshbarger
Abstract Cranial bones articulate in areas called sutures that must remain patent until skull growth is complete. Craniosynostosis is the condition that results from premature closure of one or more of the cranial vault sutures, generating facial deformities and more importantly, skull growth restrictions with the ability to severely affect brain growth. Typically, craniosynostosis can be expressed as an isolated event, or as part of syndromic phenotypes. Multiple signaling mechanisms interact during developmental stages to ensure proper and timely suture fusion. Clinical outcome is often a product of craniosynostosis subtypes, number of affected sutures and timing of premature suture fusion. The present work aimed to review the different aspects involved in the establishment of craniosynostosis, providing a close view of the cellular, molecular and genetic background of these malformations.
{"title":"Craniosynostosis: current conceptions and misconceptions","authors":"C. S. Fonteles, R. Finnell, T. George, R. Harshbarger","doi":"10.3934/genet.2016.1.99","DOIUrl":"https://doi.org/10.3934/genet.2016.1.99","url":null,"abstract":"Abstract Cranial bones articulate in areas called sutures that must remain patent until skull growth is complete. Craniosynostosis is the condition that results from premature closure of one or more of the cranial vault sutures, generating facial deformities and more importantly, skull growth restrictions with the ability to severely affect brain growth. Typically, craniosynostosis can be expressed as an isolated event, or as part of syndromic phenotypes. Multiple signaling mechanisms interact during developmental stages to ensure proper and timely suture fusion. Clinical outcome is often a product of craniosynostosis subtypes, number of affected sutures and timing of premature suture fusion. The present work aimed to review the different aspects involved in the establishment of craniosynostosis, providing a close view of the cellular, molecular and genetic background of these malformations.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248934","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}
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