Alderson, P; Aro, A R; Dragonas, T
Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...
Harper, Joyce C
Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.
Kaback, Michael; Lopatequi, Jean; Portuges, Amin Riley; Quindipan, Cathy; Pariani, Mitchel; Salimpour-Davidov, Nilou; Rimoin, David L
Israeli investigators have identified several relatively frequent disorders due to founder point mutations in Persian (Iranian) Jews, who, for nearly three centuries up to the Islamic Revolution of 1979, were completely isolated reproductively. Using a community-based model previously employed with Tay-Sachs disease prevention, we developed a pilot program for the Persian Jewish community of greater Los Angeles. We screened for mutations responsible for four relatively frequent autosomal recessive conditions in Persian Jews in which effective interventions are available for each: Pseudocholinesterase deficiency (butyryl cholinesterase deficiency); Congenital hypoaldosteronism (corticosterone methyl oxidase II); Autoimmune polyendocrinopathy (autoimmune regulatory element); and Hereditary Inclusion Body myopathy. One thousand individuals volunteered. Mutations were assessed in saliva-derived DNA and were positive for 121/1000 butyryl cholinesterase deficiency; 92/1000 Hereditary Inclusion Body myopathy; 38/1000 corticosterone methyl oxidase II; and 37/1000 autoimmune regulatory element. Ten homozygous individuals (9 butyryl cholinesterase deficiency and 1 Hereditary Inclusion Body myopathy) and 10 "at-risk" couples (seven for butyryl cholinesterase deficiency and one each for the other three disorders) were identified. These frequencies are comparable with those in Israel and indicate an extraordinary level of inbreeding, as anticipated. A carefully planned effort can be delivered to an "increased risk" community if detailed attention is given to planning and organization. However, availability of an effective intervention for those found to be "at-risk" or possibly affected, is essential before embarking.
Sharon M Lutz
Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm . Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.
Burton, Sarah K; Withrow, Kara; Arnos, Kathleen S; Kalfoglou, Andrea L; Pandya, Arti
Progress in identifying genes for deafness together with implementation of universal audiologic screening of newborns has provided the opportunity for more widespread use of molecular tests to detect genetic forms of hearing loss. Efforts to assess consumer attitudes toward these advances have lagged behind. Consumer focus groups were held to explore attitudes toward genetic advances and technologies for hearing loss, views about newborn hearing screening, and reactions to the idea of adding molecular screening for hearing loss at birth. Focus group discussions were recorded, transcribed and analyzed. Five focus groups with 44 participants including hearing parents of deaf children, deaf parents and young deaf adults were held. Focus group participants supported the use of genetic tests to identify the etiology of hearing loss but were concerned that genetic information might influence reproductive decisions. Molecular newborn screening was advocated by some; however, others expressed concern about its effectiveness. Documenting the attitudes of parents and other consumers toward genetic technologies establishes the framework for discussions on the appropriateness of molecular newborn screening for hearing loss and informs specialists about potential areas of public education necessary prior to the implementation of such screening.
After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…
Sullivan-Pyke, Chantae; Dokras, Anuja
Preimplantation genetic testing encompasses preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). PGS improves success rates of in vitro fertilization by ensuring the transfer of euploid embryos that have a higher chance of implantation and resulting in a live birth. PGD enables the identification of embryos with specific disease-causing mutations and transfer of unaffected embryos. The development of whole genome amplification and genomic tools, including single nucleotide polymorphism microarrays, comparative genomic hybridization microarrays, and next-generation sequencing, has led to faster, more accurate diagnoses that translate to improved pregnancy and live birth rates. Copyright © 2017 Elsevier Inc. All rights reserved.
Dahdouh, Elias M; Balayla, Jacques; Audibert, François; Wilson, R Douglas; Audibert, François; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Chong, Karen; Gagnon, Alain; Johnson, Jo-Ann; MacDonald, William; Okun, Nanette; Pastuck, Melanie; Vallée-Pouliot, Karine
To update and review the techniques and indications of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Discussion about the genetic and technical aspects of preimplantation reproductive techniques, particularly those using new cytogenetic technologies and embryo-stage biopsy. Clinical outcomes of reproductive techniques following the use of PGD and PGS are included. This update does not discuss in detail the adverse outcomes that have been recorded in association with assisted reproductive technologies. Published literature was retrieved through searches of The Cochrane Library and Medline in April 2014 using appropriate controlled vocabulary (aneuploidy, blastocyst/physiology, genetic diseases, preimplantation diagnosis/methods, fertilization in vitro) and key words (e.g., preimplantation genetic diagnosis, preimplantation genetic screening, comprehensive chromosome screening, aCGH, SNP microarray, qPCR, and embryo selection). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies published from 1990 to April 2014. There were no language restrictions. Searches were updated on a regular basis and incorporated in the update to January 2015. Additional publications were identified from the bibliographies of retrieved articles. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. (Table 1) BENEFITS, HARMS, AND COSTS: This update will educate readers about new preimplantation genetic concepts, directions, and technologies. The major harms and costs identified are those of assisted reproductive
Egan, Crystelle; Marakovitz, Susan; O’Rourke, Julia; Osiecki, Lisa; Illmann, Cornelia; Barton, Lauren; McLaughlin, Elizabeth; Proujansky, Rachel; Royal, Justin; Cowley, Heather; Rangel-Lugo, Martha; Pauls, David; Scharf, Jeremiah M.; Mathews, Carol A.
Genome-wide association studies (GWAS) and other emerging technologies offer great promise for the identification of genetic risk factors for complex psychiatric disorders, yet such studies are constrained by the need for large sample sizes. Web-based collection offers a relatively untapped resource for increasing participant recruitment. Therefore, we developed and implemented a novel web-based screening and phenotyping protocol for genetic studies of Tourette Syndrome (TS), a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. Participants were recruited over a 13 month period through the membership of the Tourette Syndrome Association (TSA) (n=28,878). Of the TSA members contacted, 4.3% (1,242) initiated the questionnaire, and 79.5% (987) of these were enrollment eligible. 63.9% (631) of enrolled participants completed the study by submitting phenotypic data and blood specimens. Age was the only variable that predicted study completion; children and young adults were significantly less likely to be study completers than adults 26 and older. Compared to a clinic-based study conducted over the same time period, the web-based method yielded a 60% larger sample. Web-based participants were older and more often female; otherwise, the sample characteristics did not differ significantly. TS diagnoses based on the web-screen demonstrated 100% accuracy compared to those derived from in-depth clinical interviews. Our results suggest that a web-based approach is effective for increasing the sample size for genetic studies of a relatively rare disorder and that our web-based screen is valid for diagnosing TS. Findings from this study should aid in the development of web-based protocols for other disorders. PMID:23090870
Simopoulos, A P
Screening programs for genetic diseases and characteristics have multiplied in the last 50 years. 'Genetic Screening: Programs, Principles, and Research' is the report of the Committee for the Study of Inborn Errors of Metabolism (SIEM Committee) commissioned by the Division of Medical Sciences of the National Research Council at the National Academy of Sciences in Washington, DC, published in 1975. The report is considered a classic in the field worldwide, therefore it was thought appropriate 30 years later to present the Committee's modus operandi and bring the Committee's recommendations to the attention of those involved in genetics, including organizational, educational, legal, and research aspects of genetic screening. The Committee's report anticipated many of the legal, ethical, economic, social, medical, and policy aspects of genetic screening. The recommendations are current, and future committees should be familiar with them. In 1975 the Committee stated: 'As new screening tests are devised, they should be carefully reviewed. If the experimental rate of discovery of new genetic characteristics means an accelerating rate of appearance of new screening tests, now is the time to develop the medical and social apparatus to accommodate what later on may otherwise turn out to be unmanageable growth.' What a prophetic statement that was. If the Committee's recommendations had been implemented on time, there would be today a federal agency in existence, responsive and responsible to carry out the programs and support research on various aspects of genetic screening, including implementation of a federal law that protects consumers from discrimination by their employers and the insurance industry on the basis of genetic information. Copyright 2008 S. Karger AG, Basel.
Abbing, H R
Screening activities in health care are not always useful and sometimes harmful. The mere offer of a screening test puts the individual's autonomy under constraint. With genetic (predictive and risk assessment) tests, the right to free, informed consent and to protection of privacy and medical confidentiality is even more warranted. Screening evokes many questions from the perspective of the right to health care as well as (in particular with genetic screening) from the perspective of respect for individual human rights. Fear of liability puts pressure on professional restraint not to offer every screening test available. States have to take legislative measures for guaranteeing that only those screening activities become available that can significantly contribute to individual and public health. They also should consider additional rules for protecting individual rights where those that are generally accepted in the "ordinary" medical setting (the individual patient-doctor relationship), offer insufficient protection.
Yan, LiYing; Wei, Yuan; Huang, Jin; Zhu, XiaoHui; Shi, XiaoDan; Xia, Xi; Yan, Jie; Lu, CuiLing; Lian, Ying; Li, Rong; Liu, Ping; Qiao, Jie
Preimplantation genetic diagnosis (PGD) gives couples who have a high risk of transmitting genetic disorders to their baby the chance to have a healthy offspring through embryo genetic analysis and selection. Preimplantation genetic screening (PGS) is an effective method to select euploid embryos that may prevent repeated implantation failure or miscarriage. However, how and to whom PGS should be provided is a controversial topic. The first successful case of PGD of a human being was reported in 1990, and there have been tremendous improvements in this technology since then. Both embryo biopsy and genetic technologies have been improved dramatically, which increase the accuracy and expand the indications of PGD/PGS.
Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.
The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we...... compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing ‘gold standard’ method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum....../3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox....
van El, C.G.; Pieters, T.; Cornel, M.C.
Recent decades have witnessed increasing possibilities for genetic testing and screening. In clinical genetics, the doctor's office defined a secluded space for discussion of sensitive reproductive options in cases of elevated risk for genetic disorders in individuals or their offspring. When
Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel
BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA...... and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA...... elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV...
Mastenbroek, Sebastiaan; Repping, Sjoerd
All agree that in hindsight the rapid adoption of preimplantation genetic screening (PGS) using cleavage stage biopsy and fluorescence in situ hybridization (FISH) in routine clinical practice without proper evaluation of (cost-)effectiveness basically resulted in couples paying more money for a
The aim of this work is to summarize the current knowledge about preimplantation genetic screening and diagnostics. A review article. Department of Gynecology and Obstetrics, District Hospital Šternberk, IVF Clinic, Olomouc. Preimplantation genetic testing is a complex of genetic and molecular cytogenetic examinations, which can help to detect abnormalities in embryos before transfer into the uterus of the mother. These specialized examinations are based on the latest findings in genetics and assisted reproduction. The preimplantation genetic testing is necessarily associated with a method of in vitro fertilization. It is performed on isolated blastomeres on the third day of embryo cultivation. Nowadays, it is preferred trophectoderm examination of cells from the five-day blastocysts. Generally speaking, after preimplantation genetic testing, we can select only embryos without genetic load to transfer into uterus. Preimplantation genetic testing is an important part of treatment of infertility. Complex diagnostics and treatment of infertile couples are increasingly influenced by the development and use of advanced genomic technologies. Further development and application of these modern methods require close cooperation between the field of assisted reproduction and clinical genetics.
Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel; Bancroft, Elizabeth; Vertosick, Emily; Dadaev, Tokhir; Brendler, Charles; Page, Elizabeth; Dias, Alexander; Evans, D Gareth; Rothwell, Jeanette; Maehle, Lovise; Axcrona, Karol; Richardson, Kate; Eccles, Diana; Jensen, Thomas; Osther, Palle J; van Asperen, Christi J; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Hart, Rachel; Glover, Wayne; Lam, Jimmy; Taylor, Louise; Salinas, Monica; Feliubadaló, Lidia; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Cook, Jackie; Rosario, Derek J; Buys, Saundra S; Conner, Tom; Domchek, Susan; Powers, Jacquelyn; Ausems, Margreet Gem; Teixeira, Manuel R; Maia, Sofia; Izatt, Louise; Schmutzler, Rita; Rhiem, Kerstin; Foulkes, William D; Boshari, Talia; Davidson, Rosemarie; Ruijs, Marielle; Helderman-van den Enden, Apollonia Tjm; Andrews, Lesley; Walker, Lisa; Snape, Katie; Henderson, Alex; Jobson, Irene; Lindeman, Geoffrey J; Liljegren, Annelie; Harris, Marion; Adank, Muriel A; Kirk, Judy; Taylor, Amy; Susman, Rachel; Chen-Shtoyerman, Rakefet; Pachter, Nicholas; Spigelman, Allan; Side, Lucy; Zgajnar, Janez; Mora, Josefina; Brewer, Carole; Gadea, Neus; Brady, Angela F; Gallagher, David; van Os, Theo; Donaldson, Alan; Stefansdottir, Vigdis; Barwell, Julian; James, Paul A; Murphy, Declan; Friedman, Eitan; Nicolai, Nicola; Greenhalgh, Lynn; Obeid, Elias; Murthy, Vedang; Copakova, Lucia; McGrath, John; Teo, Soo-Hwang; Strom, Sara; Kast, Karin; Leongamornlert, Daniel A; Chamberlain, Anthony; Pope, Jenny; Newlin, Anna C; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Castro, Elena; Dearnaley, David; Eyfjord, Jorunn; Falconer, Alison; Foster, Christopher S; Gronberg, Henrik; Hamdy, Freddie C; Johannsson, Oskar; Khoo, Vincent; Lubinski, Jan; Grindedal, Eli Marie; McKinley, Joanne; Shackleton, Kylie; Mitra, Anita V; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Tricker, Karen; Moss, Sue; Kote-Jarai, Zsofia; Vickers, Andrew; Lilja, Hans; Helfand, Brian T; Eeles, Rosalind A
Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml -l , PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.
Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel; Bancroft, Elizabeth; Vertosick, Emily; Dadaev, Tokhir; Brendler, Charles; Page, Elizabeth; Dias, Alexander; Evans, D Gareth; Rothwell, Jeanette; Maehle, Lovise; Axcrona, Karol; Richardson, Kate; Eccles, Diana; Jensen, Thomas; Osther, Palle J; van Asperen, Christi J; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Hart, Rachel; Glover, Wayne; Lam, Jimmy; Taylor, Louise; Salinas, Monica; Feliubadaló, Lidia; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Cook, Jackie; Rosario, Derek J; Buys, Saundra S; Conner, Tom; Domchek, Susan; Powers, Jacquelyn; Ausems, Margreet GEM; Teixeira, Manuel R; Maia, Sofia; Izatt, Louise; Schmutzler, Rita; Rhiem, Kerstin; Foulkes, William D; Boshari, Talia; Davidson, Rosemarie; Ruijs, Marielle; Helderman-van den Enden, Apollonia TJM; Andrews, Lesley; Walker, Lisa; Snape, Katie; Henderson, Alex; Jobson, Irene; Lindeman, Geoffrey J; Liljegren, Annelie; Harris, Marion; Adank, Muriel A; Kirk, Judy; Taylor, Amy; Susman, Rachel; Chen-Shtoyerman, Rakefet; Pachter, Nicholas; Spigelman, Allan; Side, Lucy; Zgajnar, Janez; Mora, Josefina; Brewer, Carole; Gadea, Neus; Brady, Angela F; Gallagher, David; van Os, Theo; Donaldson, Alan; Stefansdottir, Vigdis; Barwell, Julian; James, Paul A; Murphy, Declan; Friedman, Eitan; Nicolai, Nicola; Greenhalgh, Lynn; Obeid, Elias; Murthy, Vedang; Copakova, Lucia; McGrath, John; Teo, Soo-Hwang; Strom, Sara; Kast, Karin; Leongamornlert, Daniel A; Chamberlain, Anthony; Pope, Jenny; Newlin, Anna C; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Castro, Elena; Dearnaley, David; Eyfjord, Jorunn; Falconer, Alison; Foster, Christopher S; Gronberg, Henrik; Hamdy, Freddie C; Johannsson, Oskar; Khoo, Vincent; Lubinski, Jan; Grindedal, Eli Marie; McKinley, Joanne; Shackleton, Kylie; Mitra, Anita V; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Tricker, Karen; Moss, Sue; Kote-Jarai, Zsofia; Vickers, Andrew; Lilja, Hans; Helfand, Brian T; Eeles, Rosalind A
Background: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. Methods: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. Results: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml−l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. Conclusions: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone. PMID:29301143
Alvarenga Fernandes Sin, Olga; Michels, Helen; Nollen, Ellen A. A.
Caenorhabditis elegans comprises unique features that make it an attractive model organism in diverse fields of biology. Genetic screens are powerful to identify genes and C. elegans can be customized to forward or reverse genetic screens and to establish gene function. These genetic screens can be
Chen, Chun-Kai; Yu, Hsing-Tse; Soong, Yung-Kuei; Lee, Chyi-Long
Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body) or embryos (blastomeres or trophectoderm cells) in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH) has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows the haplotype of
Full Text Available Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body or embryos (blastomeres or trophectoderm cells in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows
Geraedts, Joep; Collins, John; Gianaroli, Luca; Goossens, Veerle; Handyside, Alan; Harper, Joyce; Montag, Markus; Repping, Sjoerd; Schmutzler, Andreas
Screening of human preimplantation embryos for numerical chromosome abnormalities has been conducted mostly at the preimplantation stage using fluorescence in situ hybridization. However, it is clear that preimplantation genetic screening (PGS) as it is currently practiced does not improve live
We used the Allin 2.0 GMO screening system from Biosmart, Switzerland to screen for the presence of genetically modified food sequences in maize meal samples, fresh fruit and vegetables from some retailers around Gaborone, Botswana. The Allin 2.0 is a multiplex PCR system for the detection of genetically modified ...
Full Text Available Amyloid protein precursor (APP, presenilin-1 (PSEN1, and presenilin-2 (PSEN2 mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD. Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series.We report here a novel update (2012-2016 of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD with an age of onset (AOO ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y. APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%. Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2 identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF biomarkers, 46 (87% had all three CSF biomarkers-total tau protein (Tau, phospho-tau protein (P-Tau, and amyloid β (Aβ42-in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification.Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the
Lanoiselée, Hélène-Marie; Nicolas, Gaël; Wallon, David; Rovelet-Lecrux, Anne; Lacour, Morgane; Rousseau, Stéphane; Richard, Anne-Claire; Pasquier, Florence; Rollin-Sillaire, Adeline; Martinaud, Olivier; Quillard-Muraine, Muriel; de la Sayette, Vincent; Boutoleau-Bretonniere, Claire; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Sarazin, Marie; le Ber, Isabelle; Epelbaum, Stéphane; Jonveaux, Thérèse; Rouaud, Olivier; Ceccaldi, Mathieu; Félician, Olivier; Godefroy, Olivier; Formaglio, Maite; Croisile, Bernard; Auriacombe, Sophie; Chamard, Ludivine; Vincent, Jean-Louis; Sauvée, Mathilde; Marelli-Tosi, Cecilia; Gabelle, Audrey; Ozsancak, Canan; Pariente, Jérémie; Paquet, Claire; Hannequin, Didier; Campion, Dominique
Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. We report here a novel update (2012-2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers-total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42-in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole
McDougall, William M; Perreira, Jill M; Reynolds, Erin C; Brass, Abraham L
Viruses impose an immense burden on human health. With the goal of treating and preventing viral infections, researchers have carried out genetic screens to improve our understanding of viral dependencies and identify potential anti-viral strategies. The emergence of CRISPR genetic screening tools has facilitated this effort by enabling host-virus screens to be undertaken in a more versatile and fidelitous manner than previously possible. Here we review the growing number of CRISPR screens which continue to increase our understanding of host-virus interactions. Copyright © 2018 Elsevier B.V. All rights reserved.
We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.
Feichtinger, Michael; Vaccari, Enrico; Carli, Luca; Wallner, Elisabeth; Mädel, Ulrike; Figl, Katharina; Palini, Simone; Feichtinger, Wilfried
The aim of this pilot study was to assess if array comparative genomic hybridization (aCGH), non-invasive preimplantation genetic screening (PGS) on blastocyst culture media is feasible. Therefore, aCGH analysis was carried out on 22 spent blastocyst culture media samples after polar body PGS because of advanced maternal age. All oocytes were fertilized by intracytoplasmic sperm injection and all embryos underwent assisted hatching. Concordance of polar body analysis and culture media genetic results was assessed. Thirteen out of 18 samples (72.2%) revealed general concordance of ploidy status (euploid or aneuploid). At least one chromosomal aberration was found concordant in 10 out of 15 embryos found to be aneuploid by both polar body and culture media analysis. Overall, 17 out of 35 (48.6%) single chromosomal aneuploidies were concordant between the culture media and polar body analysis. By analysing negative controls (oocytes with fertilization failure), notable maternal contamination was observed. Therefore, non-invasive PGS could serve as a second matrix after polar body or cleavage stage PGS; however, in euploid results, maternal contamination needs to be considered and results interpreted with caution. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Kenen, R H; Schmidt, R M
Possible latent psychological and social consequences ensuing from genetic screening programs need to be investigated during the planning phase of national genetic screening programs. The relatively few studies which have been performed to determine psychological, social, and economic consequences resulting from a genetic screening program are reviewed. Stigmatization of carrier-status, having major psychosocial implications in heterozygote genetic screening programs, is discussed and related to Erving Goffman's work in the area of stigmatization. Questions are raised regarding the relationship between such variables as religiosity and sex of the individual and acceptance of the status of newly identified carrier of a mutant gene. Severity of the deleterious gene and visibility of the carrier status are two important factors to consider in an estimation of potential stigma. Specific implications are discussed for four genetic diseases: Tay-Sachs, Sickle-Cell Anemia, Huntington's disease and Hemophilia. PMID:152585
Epidemiologists and geneticists claim that genetics has an increasing role to play in public health policies and programs in the future. Within this perspective, genetic testing and screening are instrumental in avoiding the birth of children with serious, costly or untreatable disorders. This paper
Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.
Xu, Jiawei; Niu, Wenbin; Peng, Zhaofeng; Bao, Xiao; Zhang, Meixiang; Wang, Linlin; Du, Linqing; Zhang, Nan; Sun, Yingpu
Triploidy occurred about 2-3% in human pregnancies and contributed to approximately 15% of chromosomally caused human early miscarriage. It is essential for preimplantation genetic diagnosis and screen to distinct triploidy sensitively. Here, we performed comparative investigations between MALBAC-NGS and MDA-SNP array sensitivity on triploidy detection. Self-correction and reference-correction algorism were used to analyze the NGS data. We identified 5 triploid embryos in 1198 embryos of 218 PGD and PGS cycles using MDA-SNP array, the rate of tripoidy was 4.17‰ in PGS and PGD patients. Our results indicated that the MDA-SNP array was sensitive to digyny and diandry triploidy, MALBAC-NGS combined with self and reference genome correction strategies analyze were not sensitive to detect triploidy. Our study demonstrated that triploidy occurred at 4.17‰ in PGD and PGS, MDA-SNP array could successfully identify triploidy in PGD and PGS and genomic DNA. MALBAC-NGS combined with self and reference genome correction strategies were not sensitive to triploidy.
Fantini, C; Pedinielli, J-L; Manouvrier, S
Introduction. The development of a DNA based diagnostic test has allowed for the genetic screening of many hereditary diseases. In addition to the identification of the deleterious gene, this screening process has led to the recognition of developing illnesses at high risk. In recent years, a number of genes predisposing to an inherited cancer syndrome have been identified. Our purpose in this study was to determine whether subjects at risk who test for inherited colorectal cancer, are likely to develop a higher level of psychological distress than the norm, taking into consideration the particular history of this familial disease. The demographic and psychosocial aspects of our population was described using: 1) the State Trait Anxiety Inventory (STAI), 2) the Center for Epidemiologic Studies Depression (CES-D), 3) a perceived risk for the gene carrier, 4) subjective perception of personal vulnerability and 5) the role of the medical status (affected or not), which places the subject in either predisposition or predictive testing. Results show that our population had a higher predisposition for depressive disorders (chi2=9,3. p=0.002) and a significantly higher state of anxiety (chi2=9,3. p=0.002), prior to genetic counselling, compared with other populations. We found no evidence in the medical status, nor the perceived risk. However, the assessment of one's own personal vulnerability is related to psychological distress. These results highlight the particular vulnerability of subjects undergoing genetic testing as well as showing the pertinence of proposing psychological help throughout the process of these new specific diagnoses.
Singh, Manish Pratap; Rai, Sandhya; Suyal, Shradha; Singh, Sunil Kumar; Singh, Nand Kumar; Agarwal, Akash; Srivastava, Sameer
Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFβ, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.
Besser, Andria G; Mounts, Emily L
The evolution of preimplantation genetic screening (PGS) for aneuploidy to blastocyst biopsy and more sensitive 24-chromosome screening techniques has resulted in a new diagnostic category of PGS results: those classified as mosaic. This diagnosis presents significant challenges for clinicians in developing policies regarding transfer and storage of such embryos, as well as in providing genetic counselling for patients prior to and following PGS. Given the high frequency of mosaic PGS results and the wide range of possible associated outcomes, there is an urgent need to understand how to appropriately counsel patients regarding such embryos. This is the first commentary to thoroughly address pre- and post-test genetic counselling recommendations, as well as considerations regarding prenatal screening and diagnosis. Current data on mosaic PGS results are summarized along with embryo selection considerations and potential outcomes of embryos diagnosed as mosaic. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Huang, Jin; Li, Rong; Lian, Ying; Chen, Lixue; Shi, Xiaodan; Qiao, Jie; Liu, Ping
To investigate the single blastocyst transfer in preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles. 80 PGD/PGS cycles undergoing blastocyst biopsy were studied. There were 88 warming cycles during the study period. Only one warmed blastocyst was transferred per cycle. The outcomes were followed up to the infants were born. The embryo implantation rate was 54.55% (48/88). The clinical pregnancy rate was 54.55% (48/88) per transfer cycle and 60% (48/80) per initial PGD/PGS cycle. There was no multi-pregnant in this study. The live birth rate was 42.05% (37/88) per transfer cycle and 46.25% (37/80) per initial PGD/PGS cycle. In PGD/PGS cycles, single blastocyst transfer reduces the multiple pregnancy rate without affecting the clinical outcomes.
Hamilton, Jada G.; Edwards, Heather M.; Khoury, Muin J.; Taplin, Stephen H.
The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to diseas...
Shao, Yunru; Liu, Shuling; Grinzaid, Karen
Improvements in genetic testing technologies have led to the development of expanded carrier screening panels for the Ashkenazi Jewish population; however, there are major inconsistencies in current screening practices. A 2-year pilot program was launched in Atlanta in 2010 to promote and facilitate screening for 19 Jewish genetic diseases. We analyzed data from this program, including participant demographics and outreach efforts. This retrospective analysis is based on a de-identified dataset of 724 screenees. Data were obtained through medical chart review and questionnaires and included demographic information, screening results, response to outreach efforts, and follow-up behavior and preferences. We applied descriptive analysis, chi-square tests, and logistic regression to analyze the data and compare findings with published literature. The majority of participants indicated that they were not pregnant or did not have a partner who was pregnant were affiliated with Jewish organizations and reported 100 % AJ ancestry. Overall, carrier frequency was 1 in 3.9. Friends, rabbis, and family members were the most common influencers of the decision to receive screening. People who were older, had a history of pregnancy, and had been previously screened were more likely to educate others (all p influencers who then encouraged screening in the target population. Educating influencers and increasing overall awareness were the most effective outreach strategies.
Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.
Chow, J Fc; Yeung, W Sb; Lee, V Cy; Lau, E Yl; Ho, P C; Ng, E Hy
Preimplantation genetic screening has been proposed to improve the in-vitro fertilisation outcome by screening for aneuploid embryos or blastocysts. This study aimed to report the outcome of 133 cycles of preimplantation genetic diagnosis and screening by array comparative genomic hybridisation. This study of case series was conducted in a tertiary assisted reproductive centre in Hong Kong. Patients who underwent preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening between 1 April 2012 and 30 June 2015 were included. They underwent in-vitro fertilisation and intracytoplasmic sperm injection. An embryo biopsy was performed on day-3 embryos and the blastomere was subject to array comparative genomic hybridisation. Embryos with normal copy numbers were replaced. The ongoing pregnancy rate, implantation rate, and miscarriage rate were studied. During the study period, 133 cycles of preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening were initiated in 94 patients. Overall, 112 cycles proceeded to embryo biopsy and 65 cycles had embryo transfer. The ongoing pregnancy rate per transfer cycle after preimplantation genetic screening was 50.0% and that after preimplantation genetic diagnosis was 34.9%. The implantation rates after preimplantation genetic screening and diagnosis were 45.7% and 41.1%, respectively and the miscarriage rates were 8.3% and 28.6%, respectively. There were 26 frozen-thawed embryo transfer cycles, in which vitrified and biopsied genetically transferrable embryos were replaced, resulting in an ongoing pregnancy rate of 36.4% in the screening group and 60.0% in the diagnosis group. The clinical outcomes of preimplantation genetic diagnosis and screening using comparative genomic hybridisation in our unit were comparable to those reported internationally. Genetically transferrable embryos replaced in a natural cycle may improve the ongoing pregnancy rate
Arjunan, Aishwarya; Litwack, Karen; Collins, Nick; Charrow, Joel
The Center for Jewish Genetics provides genetic education and carrier screening to individuals of Jewish descent. Carrier screening has traditionally been performed by targeted mutation analysis for founder mutations with an enzyme assay for Tay-Sachs carrier detection. The development of next-generation sequencing (NGS) allows for higher detection rates regardless of ethnicity. Here, we explore differences in carrier detection rates between genotyping and NGS in a primarily Jewish population. Peripheral blood samples or saliva samples were obtained from 506 individuals. All samples were analyzed by sequencing, targeted genotyping, triplet-repeat detection, and copy-number analysis; the analyses were carried out at Counsyl. Of 506 individuals screened, 288 were identified as carriers of at least 1 condition and 8 couples were carriers for the same disorder. A total of 434 pathogenic variants were identified. Three hundred twelve variants would have been detected via genotyping alone. Although no additional mutations were detected by NGS in diseases routinely screened for in the Ashkenazi Jewish population, 26.5% of carrier results and 2 carrier couples would have been missed without NGS in the larger panel. In a primarily Jewish population, NGS reveals a larger number of pathogenic variants and provides individuals with valuable information for family planning.Genet Med 18 12, 1214-1217.
Toiviainen, Hanna; Jallinoja, Piia; Aro, Arja R
The purpose of this study was to compare physicians', midwives' and lay people's attitudes towards genetic screening and testing to find out whether medical education and experience influence attitudes of genetic screening and testing. The study was based on comparison of answers to joint questions...... in three different cross-sectional postal surveys between October 1996 and April 1998 in Finland. Target groups were physicians (study base n=772, response rate 74%, including gynaecologists, paediatricians, general practitioners and clinical geneticists), midwives and public health nurses (collectively...
Full Text Available Abstract Background Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens. Results Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens. Conclusion Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray based deconvolution methods.
Primary amenorrhea should be investigated by karyotype analysis and selected mutation screening according to the patient's clinical features. Karyotype analyses and FMR1 gene screening is recommended in cases of POF. At present the infertility of patients with POF cannot be restored if the diagnosis is made after complete follicular depletion, but in some cases, early diagnosis by genetic investigation may instead lead to the advice of early conception or oocyte harvesting and preservation. In addition, the accumulation and annotation of array comparative genomic hybridization data might, in the near future, lead to the identification of pathogenetic copy number variations and genes involved in POF. Karyotype analysis of both partners is recommended in all couples with recurrent pregnancy loss. No routine genetic test can be recommended so far in patients with PCOS.
The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.
Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S
Hereditary hemochromatosis is considered one of the most common hereditary diseases in population of Caucasian origin. In recent years, a candidate gene for HLA-linked hemochromatosis, HFE, has been cloned, and a single G-to-A mutation resulting in a cysteine-to-tyrosine substitution (C282Y) has been identified in up to 80% of study patients with type 1 hereditary hemochromatosis. The purpose of the paper was to confirm the importance of genetic testing for HFE mutations in making the diagnosis of hemochromatosis and find out a suitable diagnostic algorithm for the indication of this form of diagnostics in patients suspected of hereditary hemochromatosis. The examination of C282Y mutation was conducted in 500 subjects. The most frequent indications for DNA analysis were hepatopathy of unknown ethiology, liver cirrhosis, diabetes mellitus, bronze skin pigmentation in connection with high serum iron concentration, elevated transferrin saturation and elevated serum ferritin levels. In our group of patients, 29 homozygotes and 75 heterozygotes for C282Y mutation were identified, 10 patients carried both C282Y and H63D mutations of HFE gene (compound heterozygotes), whereas in 386 subjects the mutation was not found. The genotype-phenotype correlation showed that 22 homozygotes had liver affection proved by imaging and/or histologic methods. Except the liver disorders, the most common symptoms of these patients were type 2 diabetes mellitus or glucose tolerance disorder (10 patients), arthritis or joint pain (9 patients) and cardiovascular disorders, such as cardiomyopathy (2 patients). Bronze skin pigmentation was present in 9 homozygotes. Transferin saturation values were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p diagnostics of this severe, but in early recognition curable disease. Early detection and phlebotomy treatment prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily
Vendrell, Xavier; Bautista-Llácer, Rosa
The genetic diagnosis and screening of preimplantation embryos generated by assisted reproduction technology has been consolidated in the prenatal care framework. The rapid evolution of DNA technologies is tending to molecular approaches. Our intention is to present a detailed methodological view, showing different diagnostic strategies based on molecular techniques that are currently applied in preimplantation genetic diagnosis. The amount of DNA from one single, or a few cells, obtained by embryo biopsy is a limiting factor for the molecular analysis. In this sense, genetic laboratories have developed molecular protocols considering this restrictive condition. Nevertheless, the development of whole-genome amplification methods has allowed preimplantation genetic diagnosis for two or more indications simultaneously, like the selection of histocompatible embryos plus detection of monogenic diseases or aneuploidies. Moreover, molecular techniques have permitted preimplantation genetic screening to progress, by implementing microarray-based comparative genome hybridization. Finally, a future view of the embryo-genetics field based on molecular advances is proposed. The normalization, cost-effectiveness analysis, and new technological tools are the next topics for preimplantation genetic diagnosis and screening. Concomitantly, these additions to assisted reproduction technologies could have a positive effect on the schedules of preimplantation studies.
Gerlai, Robert; Poshusta, Tanya L; Rampersad, Mindy; Fernandes, Yohaan; Greenwood, Tammy M; Cousin, Margot A; Klee, Eric W; Clark, Karl J
The zebrafish enjoys several advantages over other model organisms. It is small, easy to maintain, prolific, and numerous genetic tools are available for it. For example, forward genetic screens have allowed investigators to identify important genes potentially involved in a variety of functions from embryogenesis to cancer. However, despite its sophisticated behavioral repertoire, behavioral methods have rarely been utilized in forward genetic screens. Here, we employ a two-tiered strategy, a proof of concept study, to explore the feasibility of behavioral screens. We generated mutant lines using transposon-based insertional mutagenesis, allowing us to bias mutant selection with target genes expressed within the brain. Furthermore, we employed an efficient and fast behavioral pre-selection in which we investigated the locomotory response of 5-day post-fertilization old larval fish to hyperosmotic shock. Based on this assay, we selected five lines for our lower throughput secondary adult behavioral screen. The latter screen utilized tests in which computer animated image presentation and video-tracking-based automated quantification of behavior allowed us to compare heterozygous zebrafish with their wild-type siblings on their responses to a variety of stimuli. We found significant mutation induced adult behavioral alterations in 4 out of the 5 lines analyzed, including changes in response to social or fear inducing stimuli, to handling and novelty, or in habituation to novelty. We discuss the pros and cons of behavioral phenotyping and of the use of different forward genetic methods in biomedical research with zebrafish.
Lu, Lina; Lv, Bo; Huang, Kevin; Xue, Zhigang; Zhu, Xianmin; Fan, Guoping
Preimplantation genetic diagnosis/screening (PGD/PGS) aims to help couples lower the risks of transmitting genetic defects to their offspring, implantation failure, and/or miscarriage during in vitro fertilization (IVF) cycles. However, it is still being debated with regard to the practicality and diagnostic accuracy of PGD/PGS due to the concern of invasive biopsy and the potential mosaicism of embryos. Recently, several non-invasive and high-throughput assays have been developed to help overcome the challenges encountered in the conventional invasive biopsy and low-throughput analysis in PGD/PGS. In this mini-review, we will summarize the recent progresses of these new methods for PGD/PGS and discuss their potential applications in IVF clinics.
Baptista, Miguel Viana; Ferreira, Susana; Pinho-E-Melo, Teresa; Carvalho, Marta; Cruz, Vítor T; Carmona, Cátia; Silva, Fernando A; Tuna, Assunção; Rodrigues, Miguel; Ferreira, Carla; Pinto, Ana A N; Leitão, André; Gabriel, João Paulo; Calado, Sofia; Oliveira, João Paulo; Ferro, José M
Fabry disease is an X-linked monogenic disorder caused by mutations in the GLA gene. Recent data suggest that stroke in young adults may be associated with Fabry disease. We aimed to ascertain the prevalence of this disorder among young adult patients with stroke in Portugal by GLA genotyping. During 1 year, all patients aged 18 to 55 years with first-ever stroke, who were admitted into any of 12 neurology hospital departments in Portugal, were prospectively enrolled (n=625). Ischemic stroke was classified according to Trial of Org 10172 in Acute Stroke Treatment criteria. Alpha-galactosidase activity was further assayed in all patients with GLA mutations. Four hundred ninety-three patients (mean age, 45.4 years; 61% male) underwent genetic analyses: 364 with ischemic stroke, 89 with intracerebral hemorrhage, 26 with subarachnoid hemorrhage, and 14 with cerebral venous thrombosis. Twelve patients had missense GLA mutations: 9 with ischemic stroke (p.R118C: n=4; p.D313Y: n=5), including 5 patients with an identified cause of stroke (cardiac embolism: n=2; small vessel disease: n=2; other cause: n=1), 2 with intracerebral hemorrhage (p.R118C: n=1; p.D313Y: n=1), and one with cerebral venous thrombosis (p.R118C: n=1). Leukocyte alpha-galactosidase activity was subnormal in the hemizygous males and subnormal or low-normal in the heterozygous females. Estimated prevalence of missense GLA mutations was 2.4% (95% CI, 1.3% to 4.1%). Despite a low diagnostic yield, screening for GLA mutations should probably be considered in different types of stroke. Restricting investigation to patients with cryptogenic stroke may underestimate the true prevalence of Fabry disease in young patients with stroke.
Barad, David H; Darmon, Sarah K; Kushnir, Vitaly A; Albertini, David F; Gleicher, Norbert
Our objective was to estimate the contribution of preimplantation genetic screening to in vitro fertilization pregnancy outcomes in donor oocyte-recipient cycles. This was a retrospective cross-sectional study of US national data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2005 and 2013. Society for Assisted Reproductive Technology Clinic Outcome Reporting relies on voluntarily annual reports by more than 90% of US in vitro fertilization centers. We evaluated pregnancy and live birth rates in donor oocyte-recipient cycles after the first embryo transfer with day 5/6 embryos. Statistical models, adjusted for patient and donor ages, number of embryos transferred, race, infertility diagnosis, and cycle year were created to compare live birth rates in 392 preimplantation genetic screening and 20,616 control cycles. Overall, pregnancy and live birth rates were significantly lower in preimplantation genetic screening cycles than in control cycles. Adjusted odds of live birth for preimplantation genetic screening cycles were reduced by 35% (odds ratio, 0.65, 95% confidence interval, 0.53-0.80; P cycles over the past 9 years, has not been associated with improved odds of live birth or reduction in miscarriage rates. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available Preimplantation genetic diagnosis (PGD is a clinically feasible technology to prevent the transmission of monogenic inherited disorders in families afflicted the diseases to the future offsprings. The major technical hurdle is it does not have a general formula for all mutations, thus different gene locus needs individualized, customized design to make the diagnosis accurate enough to be applied on PGD, in which the quantity of DNA is scarce, whereas timely result is sometimes requested if fresh embryo transfer is desired. On the other hand, preimplantation genetic screening (PGS screens embryo with aneuploidy and was also known as PGD-A (A denotes aneuploidy in order to enhance the implantation rates as well as livebirth rates. In contrasts to PGD, PGS is still under ferocious debate, especially recent reports found that euploid babies were born after transferring the aneuploid embryos diagnosed by PGS back to the womb and only very few randomized trials of PGS are available in the literature. We have been doing PGD and/or PGS for more than 10 years as one of the core PGD/PGS laboratories in Taiwan. Here we provide a concise review of PGD/PGS regarding its current status, both domestically and globally, as well as its future challenges.
Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C; Weile, Jochen; Jacob, Yves; Verby, Marta; Ozturk, Sedide B; Li, Siyang; Cote, Atina G; Mosca, Roberto; Knapp, Jennifer J; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Sahni, Nidhi; Yi, Song; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F; Wong, Cassandra; Musa, Louai; Snider, Jamie; Liu, Yi-Chun; Yu, Haiyuan; Braun, Pascal; Stagljar, Igor; Hao, Tong; Calderwood, Michael A; Pelletier, Laurence; Aloy, Patrick; Hill, David E; Vidal, Marc; Roth, Frederick P
High-throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome-scale interaction mapping. Here, we report Barcode Fusion Genetics-Yeast Two-Hybrid (BFG-Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG-Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein-pair barcodes that can be quantified via next-generation sequencing. We applied BFG-Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG-Y2H increases the efficiency of protein matrix screening, with quality that is on par with state-of-the-art Y2H methods. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.
van der Tol, L.; Smid, B. E.; Poorthuis, B. J. H. M.; Biegstraaten, M.; Deprez, R. H. Lekanne; Linthorst, G. E.; Hollak, C. E. M.
Screening for Fabry disease (FD) reveals a high prevalence of individuals with α-galactosidase A (GLA) genetic variants of unknown significance (GVUS). These individuals often do not express characteristic features of FD. A systematic review on FD screening studies was performed to interpret the
Full Text Available Background: Selection of the best embryo for transfer is very important in assisted reproductive technology (ART. Using morphological assessment for this selection demonstrated that the correlation between embryo morphology and implantation potential is relatively weak. On the other hand, aneuploidy is a key genetic factor that can influence human reproductive success in ART. Objective: The aim of this lab trial study was to evaluate the incidence of aneuploidies in five chromosomes in the morphologically high-quality embryos from young patients undergoing ART for sex selection. Materials and Methods: A total of 97 high quality embryos from 23 women at the age of 37or younger years that had previously undergone preimplantation genetic screening for sex selection were included in this study. After washing, the slides of blastomeres from embryos of patients were reanalyzed by fluorescence in-situ hybridization for chromosomes 13, 18 and 21. Results: There was a significant rate of aneuploidy determination in the embryos using preimplantation genetic screening for both sex and three evaluated autosomal chromosomes compared to preimplantation genetic screening for only sex chromosomes (62.9% vs. 24.7%, p=0.000. The most frequent detected chromosomal aneuploidy was trisomy or monosomy of chromosome 13. Conclusion: There is considerable numbers of chromosomal abnormalities in embryos generated in vitro which cause in vitro fertilization failure and it seems that morphological characterization of embryos is not a suitable method for choosing the embryos without these abnormalities
Mallia, Pierre; ten Have, Henk
Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic screening and testing. It is important therefore to analyse the philosophical implications of this approach onto the bioethical world, where much disagreement occurs on fundamental issues. It is Catholic basic teaching to recognize and see God's hand in plurality, not merely as a cliche and then doing what we feel is right, but to recognize how to live in a pluralistic world. We recognize, in agreement with these theologians, that in order for a Trinitarian mode of understanding to be used by those doing bioethical debate, there is a need to depart from fundamentalism.
Niimi, Hideki; Ogawa, Tomomi; Note, Rhougou; Hayashi, Shirou; Ueno, Tomohiro; Harada, Kenu; Uji, Yoshinori; Kitajima, Isao
In recent years, genetic diagnostics of pathogenic splicing abnormalities are increasingly recognized as critically important in the clinical genetic diagnostics. It is reported that approximately 10% of pathogenic mutations causing human inherited diseases are splicing mutations. Nonetheless, it is still difficult to identify splicing abnormalities in routine genetic diagnostic settings. Here, we studied two different kinds of cases with splicing abnormalities. The first case is a protein S deficiency. Nucleotide analyses revealed that the proband had a previously reported G to C substitution in the invariant AG dinucleotide at the splicing acceptor site of intronl/exon2, which produces multiple splicing abnormalities resulting in protein S deficiency. The second case is an antithrombin (AT) deficiency. This proband had a previously reported G to A substitution, at nucleotide position 9788 in intron 4, 14 bp in front of exon 5, which created a de novo exon 5 splice site and resulted in AT deficiency. From a practical standpoint, we discussed the pitfalls, attentions, and screening approaches in genetic diagnostics of pathogenic splicing abnormalities. Due to the difficulty with full-length sequence analysis of introns, and the lack of RNA samples, splicing mutations may escape identification. Although current genetic testing remains to be improved, to screen for splicing abnormalities more efficiently, it is significant to use an appropriate combination of various approaches such as DNA and/or RNA samples, splicing mutation databases, bioinformatic tools to detect splice sites and cis-regulatory elements, and in vitro and/or in vivo experimentally methods as needed.
Prins, J.C.P.; Smant, G.; Jansen, R.C.
Genetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome
Graffigna, Guendalina; Leone, Daniela; Vegni, Elena
How do patients with thrombophilia experience a physician's request to undergo a genetic test? How do they experience the test outcome? To answer these questions, we conducted an interpretative phenomenological analysis study, based on 10 in-depth interviews with patients who underwent genetic testing for thrombophilia in Italy, half with positive and half with negative results. The experience of undergoing genetic screening for thrombophilia plays an important role in reconfiguring patients' signification of their illness experience. A positive outcome becomes a cue to reorganize in a more adaptive way the illness meaning at the cognitive and emotive levels, whereas a negative outcome appears more distressing and confusing. As a clinical implication of the study, clinicians should consider communicating carefully with the patients regardless from the positive/negative test results and they should explore the patient's specific reaction and understanding of test result.
Burton-Chase, Allison M.; Hovick, Shelly R.; Peterson, Susan K.; Marani, Salma K.; Vernon, Sally W.; Amos, Christopher I.; Frazier, Marsha L.; Lynch, Patrick M.; Gritz, Ellen R.
Purpose This study examined colonoscopy adherence and attitudes towards colorectal cancer (CRC) screening in individuals who underwent Lynch syndrome genetic counseling and testing. Methods We evaluated changes in colonoscopy adherence and CRC screening attitudes in 78 cancer-unaffected relatives of Lynch syndrome mutation carriers before pre-test genetic counseling (baseline) and at 6 and 12 months post-disclosure of test results (52 mutation-negative, 26 mutation-positive). Results While both groups were similar at baseline, at 12 months post-disclosure, a greater number of mutation-positive individuals had had a colonoscopy compared with mutation-negative individuals. From baseline to 12 months post-disclosure, the mutation-positive group demonstrated an increase in mean scores on measures of colonoscopy commitment, self-efficacy, and perceived benefits of CRC screening, and a decrease in mean scores for perceived barriers to CRC screening. Mean scores on colonoscopy commitment decreased from baseline to 6 months in the mutation-negative group. Conclusion Adherence to risk-appropriate guidelines for CRC surveillance improved after genetic counseling and testing for Lynch syndrome. Mutation-positive individuals reported increasingly positive attitudes toward CRC screening after receiving genetic test results, potentially reinforcing longer term colonoscopy adherence. PMID:23414081
This study aimed at providing a means for probing the molecular genetic organization of B.fragilis, particularly those strains where the DNA repair mechanisms had been described. The following routes of investigation were followed: the bacteriocin of B.fragilis BF-1; the investigation of any plasmids which might be discovered, with the aim of constructing a hybrid plasmid which might replicate in both E.coli and B.fragilis; and the preparation of a genetic library which could be screened for Bacteroides genes which might function in E.coli. Should any genes be isolated by screening the library they were to be studied with regard to their expression and regulation in E.coli. The above assays make use of radioactive markers such as 14 C, 35 S, 32 P, and 3 H in the labelling of RNA, plasmids and probes
This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).
Jyothi Kiran Kohli
Full Text Available BACKGROUND Genetic diseases are one of the major causes of hospital admissions due to disability and mortality particularly among children (1:5 children of hospital admission either partially/completely as distribution of genetic diseases is not related to socioeconomic background, which implies that developing world has a large number of genetic diseases largely left uncared for, i.e. overall incidence of foetal/neonatal loss due to genetic/genetic environmental causes are as follows: 1:50 newborns have major congenital abnormality, 1:100 have a unifactorial disorder, 1:200 have a major chromosomal abnormality before birth. Diagnosis of chromosomal anomalies in foetus is one of the most important challenges in modern perinatology as invasive or noninvasive methods. The aim of the study is to review on cytogenetic evaluation of CVS obtained (transcervically during first trimester of pregnancy by direct karyotyping of tissue. MATERIALS AND METHODS This study was conducted in 2001 in Department of Anatomy along with Obstetrics and Gynaecology Department, LNJP Hospital. 37 healthy cases with 6-12 weeks of gestational age coming for medical termination of pregnancy were included in the study. After written informed consent for procedure, ultrasound-guided transcervical chorionic villus sampling was done (Brambati’s method. Tissue procured was then processed for direct karyotyping and studied. Metaphase spreads were photographed and karyotypes prepared and studied. RESULTS Out of 37 pregnant females, 30 samples were successfully prepared and processed by Direct method out of which 23 were normal female (46, XX and 7 were normal male (46, XY. No normal anomaly was detected. Best biopsies were obtained with 8-12 weeks gestation. G Banding could not be performed as chromosome obtained were found to be resistant to banding. CONCLUSIONS To summarise chromosome preparations obtained from CVS by Direct method has advantage of providing sufficient number
Holton, Avery E; Canary, Heather E; Wong, Bob
A growing body of research has given attention to issues surrounding genetic testing, including expanded carrier screening (ECS), an elective medical test that allows planning or expecting parents to consider the potential occurrence of genetic diseases and disorders in their children. These studies have noted the role of the mass media in driving public perceptions about such testing, giving particular attention to ways in which coverage of genetics and genetic testing broadly may drive public attitudes and choices concerning the morality, legality, ethics, and parental well-being involved in genetic technologies. However, few studies have explored how mass media are covering the newer test, ECS. Drawing on health-related framing studies that have shown in varying degrees the impact particular frames such as gain/loss and thematic/episodic can have on the public, this study examines the frame selection employed by online media in its coverage of ECS. This analysis-combined with an analysis of the sources and topics used in such coverage and how they relate to selected frames-helps to clarify how mass media are covering an increasingly important medical test and offers considerations of how such coverage may inform mass media scholarship as well as health-related practices.
Panayiotakis, G.; Nomikos, C.; Bakas, A.; Proimos, B.
We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors)
Panayiotakis, G; Nomikos, C; Bakas, A; Proimos, B [Medical Physics Department, University of Patras, 265 00 Patras, Greece (Greece)
We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors). 12 refs, 3 figs.
Jonas, Susanna; Wild, Claudia; Schamberger, Chantal
mastectomy (PM) reduces the relative breast cancer risk by approximately 90%. The question is if PM has an impact on mortality. The acceptance of PM is culture-dependent. Colectomy can be used as a prophylactic (FAP) and therapeutic method. After surgery, the cancer risk remains high and so early detection examinations are still necessary. EVIDENCE-BASED STATEMENTS: The evidence is often fragmentary and of limited quality. For objective test result presentation information about sensitivity, specificity, positive predictive value, and number needed to screen and treat, respectively, are necessary. New identification of mutations and demand will lead to an increase of predictive genetic counselling and testing. There is a gap between predictive genetic diagnosis and prediction, prevention, early detection and surgical interventions. These circumstances require a basic strategy. Since predictive genetic diagnosis is a very sensitive issue it is important to deal with it carefully in order to avoid inappropriate hopes. Thus, media, experts and politicians need to consider opportunities and limitations in their daily decision-making processes.
Kerruish, Nicola J; Healey, Dione M; Gray, Andrew R
Little is known about the psychosocial consequences of testing newborns for genetic susceptibility to multifactorial diseases. This study reports quantitative psychosocial evaluations of parents and children 12 years after screening for type 1 diabetes (T1D). Two parent-child cohorts participated: children at increased genetic risk of T1D and children at low genetic risk. T1D risk status was determined at birth as part of a prospective study investigating potential environmental triggers of autoimmunity. Parent measures included ratings of children's emotional, behavioural and social functioning (Child Behaviour Checklist) and parenting style (Alabama Parenting Questionnaire). Child self-concept was assessed using the self-description questionnaire (SDQ1). Statistical analyses were conducted to test for differences between the groups. Twelve years after testing there was no evidence that knowledge of a child's increased genetic risk of T1D adversely affected parental ratings of their child's emotional, behavioural or social functioning, or impacted upon parenting style. There was no adverse effect upon the child's assessment of their self-concept. This study provides important preliminary data concerning longer-term psychosocial effects of incorporating tests for genetic risk of complex disorders into NBS panels. While it is reassuring that no significant adverse effects have been detected, more data will be required to adequately inform policy. PMID:28120838
Canter, E F
The emergence of genetic screening techniques will permit employers to exclude hypersusceptible individuals from potentially hazardous workplace environments. The denial of employment opportunities to these individuals, however, may constitute discrimination. This Note analyzes genetic screening cases with respect to currently available remedies contained in Title VII of the Civil Rights Act of 1964 and the Rehabilitation Act of 1973. The Note concludes that Title VII claims may succeed but only in limited circumstances and that Rehabilitation Act claims will encounter numerous obstacles to relief. Additionally, the Note discusses some of the implications of the use of genetic screening in the workplace.
Kauffman, Tia L.; Wilfond, Benjamin S.; Jarvik, Gail P.; Leo, Michael C.; Lynch, Frances L.; Reiss, Jacob A.; Richards, C. Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O.; Goddard, Katrina A.B.
Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results...
Koppelman, GH; Postma, DS; Meijer, G.
Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define
Malogajski, Jelena; Jansen, Marleen E; Ouburg, Sander; Ambrosino, Elena; Terwee, Caroline B; Morré, Servaas A
This study aims to identify elements perceived by Dutch fertility specialists as barriers and facilitators for the introduction of genetic testing, and their attitudes towards the use of genetic information. The genetic test would be implemented in routine screening for tubal pathology and identifies SNPs relevant for the immune response causing tubal pathology. Experienced reproductive specialists working in Dutch Academic Hospitals were interviewed. Based on the results of four interviews a questionnaire was developed and used to survey medical doctors in six out of eight Dutch Academic hospitals. 60.4% (n=91) stated that the addition of genetic markers to the Chlamydia trachomatis antibody test (CAT) in screening for tubal pathology would increase screening accuracy. 68.2% (n=90) agreed they would require additional training on clinical genetics. Clinical utility (91.2%, n=91) and cost-effectiveness (95.6%, n=91) were recognized by the respondents as important factors in gaining support for the new screening strategy. In summary, respondents showed a positive attitude towards the implementation of a genetic test combined with CAT for tubal factor infertility (TFI) screening. To gain their support the majority of respondents agreed that clinical utility, specifically cost-effectiveness, is an important factor. Comprehensive research about economic implications and utility regarding the introduction of genomic markers should be the next step in the implementation strategy. Furthermore, education and training would need to be developed and offered to fertility care professionals about genetic markers, their interpretation, and implications for clinical decision-making. Copyright © 2017 Elsevier B.V. All rights reserved.
Khoury Muin J
Full Text Available Abstract Background Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM, a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. Results The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. Conclusion GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.
Eijzenga, W.; Bleiker, E.M.A.; Hahn, D.E.E.; Kluijt, I.; Sidharta, G.N.; Gundy, C.; Aaronson, N.K.
Background: Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific
Chambliss, Allison B; Resnick, Molly; Petrides, Athena K; Clarke, William A; Marzinke, Mark A
Current methods for the detection of single nucleotide polymorphisms (SNPs) associated with aberrant drug-metabolizing enzyme function are hindered by long turnaround times and specialized techniques and instrumentation. In this study, we describe the development and validation of a high-resolution melting (HRM) curve assay for the rapid screening of variant genotypes for targeted genetic polymorphisms in the cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A5. Sequence-specific primers were custom-designed to flank nine SNPs within the genetic regions of aforementioned drug metabolizing enzymes. PCR amplification was performed followed by amplicon denaturation by precise temperature ramping in order to distinguish genotypes by melting temperature (Tm). A standardized software algorithm was used to assign amplicons as 'reference' or 'variant' as compared to duplicate reference sequence DNA controls for each SNP. Intra-assay (n=5) precision of Tms for all SNPs was ≤0.19%, while inter-assay (n=20) precision ranged from 0.04% to 0.21%. When compared to a reference method of Sanger sequencing, the HRM assay produced no false negative results, and overcall frequency ranged from 0% to 26%, depending on the SNP. Furthermore, HRM genotyping displayed accuracy over input DNA concentrations ranging from 10 to 200 ng/μL. The presented assay provides a rapid method for the screening for genetic variants in targeted CYP450 regions with a result of 'reference' or 'variant' available within 2 h from receipt of extracted DNA. The method can serve as a screening approach to rapidly identify individuals with variant sequences who should be further investigated by reflexed confirmatory testing for aberrant cytochrome P450 enzymatic activity. Rapid knowledge of variant status may aid in the avoidance of adverse clinical events by allowing for dosing of normal metabolizer patients immediately while identifying the need to wait for confirmatory testing in those patients who are
Research during the past year has moved ahead on several fronts. A major compilation of all the genetic mapping data for the yeast Saccharomyces cerevisiae has been completed. The map describes the location of over 300 genes on 17 chromosomes. A report on this work will appear in Microbiological Reviews in December 1980. Recombinant DNA procedures have been introduced into the experiments and RAD52 (one of the genes involved in recombination and repair damage), has been successfully cloned. This clone will be used to determine the gene product. Diploid cells homozygous for RAD52 have exceptionally high frequencies of mitotic loss of chromosomes. This loss is stimulated by ionizing radiation. This effect is a very significant finding. The effect has also been seen with certain other RAD mutants
Seggers, Jorien; Haadsma, Maaike L.; Bastide-van Gemert, Sacha la; Heineman, Maas Jan; Kok, Joke H.; Middelburg, Karin J.; Roseboom, Tessa J.; Schendelaar, Pamela; van den Heuvel, Edwin R.; Hadders-Algra, Mijna
Recent studies suggest that in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with suboptimal cardiometabolic outcome in offspring. It is unknown whether preimplantation genetic screening (PGS), which involves embryo biopsy, affects blood pressure (BP),
Seggers, Jorien; Haadsma, Maaike L.; la Bastide-van Gemert, Sacha; Heineman, Maas Jan; Kok, Joke H.; Middelburg, Karin J.; Roseboom, Tessa J.; Schendelaar, Pamela; Van den Heuvel, Edwin R.; Hadders-Algra, Mijna
BACKGROUND: Recent studies suggest that in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with suboptimal cardiometabolic outcome in offspring. It is unknown whether preimplantation genetic screening (PGS), which involves embryo biopsy, affects blood pressure
Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based
Dondorp, W; De Wert, G; Pennings, G; Shenfield, F; Devroey, P; Tarlatzis, B; Barri, P; Diedrich, K; Eichenlaub-Ritter, U; Tüttelmann, F; Provoost, V
This Task Force document explores the ethical issues involved in the debate about the scope of genetic screening of gamete donors. Calls for expanded donor screening arise against the background of both occasional findings of serious but rare genetic conditions in donors or donor offspring that were not detected through present screening procedures and the advent of new genomic technologies promising affordable testing of donors for a wide range of conditions. Ethical principles require that all stakeholders' interests are taken into account, including those of candidate donors. The message of the profession should be that avoiding all risks is impossible and that testing should remain proportional.
Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.
Sapiro, Anne L.; Ihry, Robert J.; Buhr, Derek L.; Konieczko, Kevin M.; Ives, Sarah M.; Engstrom, Anna K.; Wleklinski, Nicholas P.; Kopish, Kristin J.; Bashirullah, Arash
Mutagenesis screens are a staple of classical genetics. Chemical-induced mutations, however, are often difficult and time-consuming to identify. Here, we report that recombination analysis with pairs of dominant visible markers provides a rapid and reliable strategy to map mutations in Drosophila melanogaster. This method requires only two generations and a total of six crosses in vials to estimate the genetic map position of the responsible lesion with high accuracy. This genetic map positio...
Cappa, Claudia; Giulivi, Sara; Schilirò, Antonino; Bastiani, Luca; Muzio, Carlo; Meloni, Fabrizio
The aim of the present research is to investigate the prevalence of Specific Learning Disorders (SLD) in Ogliastra, an area of the island of Sardinia, Italy. Having experienced centuries of isolation, Ogliastra has become a high genetic homogeneity area, and is considered particularly interesting for studies on different kinds of pathologies. Here we are going to describe the results of a screening carried out throughout 2 consecutive years in 49 second grade classes (24 considered in the first year and 25 in the second year of the study) of the Ogliastra region. A total of 610 pupils (average age 7.54 years; 293 female, 317 male) corresponding to 68.69% of all pupils who were attending second grade in the area, took part in the study. The tool used for the screening was "RSR-DSA. Questionnaire for the detection of learning difficulties and disorders", which allowed the identification of 83 subjects at risk (13.61% of the whole sample involved in the study). These subjects took part in an enhancement training program of about 6 months. After the program, pupils underwent assessment for reading, writing and calculation abilities, as well as cognitive assessment. According to the results of the assessment, the prevalence of SLDs is 6.06%. For what concerns dyslexia, 4.75% of the total sample manifested this disorder either in isolation or in comorbidity with other disorders. According to the first national epidemiological investigation carried out in Italy, the prevalence of dyslexia is 3.1-3.2%, which is lower than the prevalence obtained in the present study. Given the genetic basis of SLDs, this result, together with the presence of several cases of SLD in isolation (17.14%) and with a 3:1 ratio of males to females diagnosed with a SLD, was to be expected in a sample coming from a high genetic homogeneity area. Copyright © 2015 Elsevier Ltd. All rights reserved.
Mallia, P.; Have, H.A.M.J. ten
Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic
Dixon, M.L.; Mortimer, R.K.
Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. The authors describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant increases in the frequencies of each genetic change, increases in the absolute numbers of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints. (Auth.)
Quarterman, Josh; Kim, Soo Rin; Kim, Pan-Jun; Jin, Yong-Su
In order to determine beneficial gene deletions for ethanol production by the yeast Saccharomyces cerevisiae, we performed an in silico gene deletion experiment based on a genome-scale metabolic model. Genes coding for two oxidative phosphorylation reactions (cytochrome c oxidase and ubiquinol cytochrome c reductase) were identified by the model-based simulation as potential deletion targets for enhancing ethanol production and maintaining acceptable overall growth rate in oxygen-limited conditions. Since the two target enzymes are composed of multiple subunits, we conducted a genetic screening study to evaluate the in silico results and compare the effect of deleting various portions of the respiratory enzyme complexes. Over two-thirds of the knockout mutants identified by the in silico study did exhibit experimental behavior in qualitative agreement with model predictions, but the exceptions illustrate the limitation of using a purely stoichiometric model-based approach. Furthermore, there was a substantial quantitative variation in phenotype among the various respiration-deficient mutants that were screened in this study, and three genes encoding respiratory enzyme subunits were identified as the best knockout targets for improving hexose fermentation in microaerobic conditions. Specifically, deletion of either COX9 or QCR9 resulted in higher ethanol production rates than the parental strain by 37% and 27%, respectively, with slight growth disadvantages. Also, deletion of QCR6 led to improved ethanol production rate by 24% with no growth disadvantage. The beneficial effects of these gene deletions were consistently demonstrated in different strain backgrounds and with four common hexoses. The combination of stoichiometric modeling and genetic screening using a systematic knockout collection was useful for narrowing a large set of gene targets and identifying targets of interest. Copyright © 2014 Elsevier B.V. All rights reserved.
Full Text Available To select cytogenetically normal embryos, preimplantation genetic diagnosis (PGD aneuploidy screening (AS is used in numerous centers around the world. Chromosomal abnormalities lead to developmental problems, implantation failure, and early abortion of embryos. The usefulness of PGD in identifying single-gene diseases, human leukocyte antigen typing, X-linked diseases, and specific genetic diseases is well-known. In this review, preimplantation embryo genetics, PGD research studies, and the European Society of Human Reproduction and Embryology PGD Consortium studies and reports are examined. In addition, criteria for embryo selection, technical aspects of PGD-AS, and potential noninvasive embryo selection methods are described. Indications for PGD and possible causes of discordant PGD results between the centers are discussed. The limitations of fluorescence in situ hybridization, and the advantages of the array comparative genomic hybridization are included in this review. Although PGD-AS for patients of advanced maternal age has been shown to improve in vitro fertilization outcomes in some studies, to our knowledge, there is not sufficient evidence to use advanced maternal age as the sole indication for PGD-AS. PGD-AS might be harmful and may not increase the success rates of in vitro fertilization. At the same time PGD, is not recommended for recurrent implantation failure and unexplained recurrent pregnancy loss.
Song, Zhang-yue; Tian, Jing-luan; Fu, Wei-zhe; Li, Lin; Lu, Ling-hong; Zhou, Lian; Shan, Zhi-hui; Tang, Gui-xiang; Shou, Hui-xia
The Agrobacterium-mediated transformation system is the most commonly used method in soybean transformation. Screening of soybean genotypes favorable for Agrobacterium-infection and tissue regeneration is the most important step to establish an efficient genetic transformation system. In this study, twenty soybean genotypes that originated from different soybean production regions in China were screened for transient infection, regeneration capacity, and stable transgenic efficiency. Three genotypes, Yuechun 04-5, Yuechun 03-3, and Tianlong 1, showed comparable stable transgenic efficiencies with that of the previously reported American genotypes Williams 82 and Jack in our experimental system. For the Tianlong 1, the average stable transformation efficiency is 4.59%, higher than that of control genotypes (Jack and Williams 82), which is enough for further genomic research and genetic engineering. While polymerase chain reaction (PCR), LibertyLink strips, and β-glucuronidase (GUS) staining assays were used to detect the insertion and expression of the transgene, leaves painted with 135 mg/L Basta could efficiently identify the transformants. PMID:23549846
Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric
In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia. PMID:24860163
Kim, Hyun-Joong; Ryu, Ji-Oh; Song, Ji-Yeon; Kim, Hae-Yeong
In the detection of Shigella species using molecular biological methods, previously known genetic markers for Shigella species were not sufficient to discriminate between Shigella species and diarrheagenic Escherichia coli. The purposes of this study were to screen for genetic markers of the Shigella genus and four Shigella species through comparative genomics and develop a multiplex polymerase chain reaction (PCR) for the detection of shigellae and Shigella species. A total of seven genomic DNA sequences from Shigella species were subjected to comparative genomics for the screening of genetic markers of shigellae and each Shigella species. The primer sets were designed from the screened genetic markers and evaluated using PCR with genomic DNAs from Shigella and other bacterial strains in Enterobacteriaceae. A novel Shigella quintuplex PCR, designed for the detection of Shigella genus, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, was developed from the evaluated primer sets, and its performance was demonstrated with specifically amplified results from each Shigella species. This Shigella multiplex PCR is the first to be reported with novel genetic markers developed through comparative genomics and may be a useful tool for the accurate detection of the Shigella genus and species from closely related bacteria in clinical microbiology and food safety.
Cagnon, Caroline; Mirabella, Boris; Nguyen, Hoa Mai; Beyly-Adriano, Audrey; Bouvet, Séverine; Cuiné, Stéphan; Beisson, Fred; Peltier, Gilles; Li-Beisson, Yonghua
Oils produced by microalgae are precursors to biodiesel. To achieve a profitable production of biodiesel from microalgae, identification of factors governing oil synthesis and turnover is desirable. The green microalga Chlamydomonas reinhardtii is amenable to genetic analyses and has recently emerged as a model to study oil metabolism. However, a detailed method to isolate various types of oil mutants that is adapted to Chlamydomonas has not been reported. We describe here a forward genetic approach to isolate mutants altered in oil synthesis and turnover from C. reinhardtii. It consists of a three-step screening procedure: a primary screen by flow cytometry of Nile red stained transformants grown in 96-deep-well plates under three sequential conditions (presence of nitrogen, then absence of nitrogen, followed by oil remobilization); a confirmation step using Nile red stained biological triplicates; and a validation step consisting of the quantification by thin layer chromatography of oil content of selected strains. Thirty-one mutants were isolated by screening 1,800 transformants generated by random insertional mutagenesis (1.7%). Five showed increased oil accumulation under the nitrogen-replete condition and 13 had altered oil content under nitrogen-depletion. All mutants were affected in oil remobilization. This study demonstrates that various types of oil mutants can be isolated in Chlamydomonas based on the method set-up here, including mutants accumulating oil under optimal biomass growth. The strategy conceived and the protocol set-up should be applicable to other microalgal species such as Nannochloropsis and Chlorella, thus serving as a useful tool in Chlamydomonas oil research and algal biotechnology.
Granberg, Candace F; Harrison, Steven M; Dajusta, Daniel; Zhang, Shaohua; Hajarnis, Sachin; Igarashi, Peter; Baker, Linda A
Although the cause of prune belly syndrome is unknown, familial evidence suggests a genetic component. Recently 2 nonfamilial cases of prune belly syndrome with chromosome 17q12 deletions encompassing the HNF1β gene have made this a candidate gene for prune belly syndrome. To date, there has been no large-scale screening of patients with prune belly syndrome for HNF1β mutations. We assessed the role of HNF1β in prune belly syndrome by screening for genomic mutations with functional characterization of any detected mutations. We studied patients with prune belly syndrome who were prospectively enrolled in our Pediatric Genitourinary DNA Repository since 2001. DNA from patient samples was amplified by polymerase chain reaction, sequenced for coding and splice regions of the HNF1β gene, and compared to control databases. We performed functional assay testing of the ability of mutant HNF1β to activate a luciferase construct with an HNF1β DNA binding site. From 32 prune belly syndrome probands (30 males, 2 females) HNF1β sequencing detected a missense mutation (V61G) in 1 child with prune belly syndrome. Absent in control databases, V61G was previously reported in 2 patients without prune belly syndrome who had congenital genitourinary anomalies. Functional testing showed similar luciferase activity compared to wild-type HNF1β, suggesting the V61G substitution does not disturb HNF1β function. One genomic HNF1β mutation was detected in 3% of patients with prune belly syndrome but found to be functionally normal. Thus, functionally significant HNF1β mutations are uncommon in prune belly syndrome, despite case reports of HNF1β deletions. Further genetic study is necessary, as identification of the genetic basis of prune belly syndrome may ultimately lead to prevention and improved treatments for this rare but severe syndrome. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Full Text Available We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs. New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.
Datukishvili, Nelly; Kutateladze, Tamara; Gabriadze, Inga; Bitskinashvili, Kakha; Vishnepolsky, Boris
We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.
Wu, L.; Luo, P.; Di, D.W.; Wang, L.; Wang, M.; Lu, C.K.; Wei, S.D.; Zhang, L.; Zhang, T.Z.; Amakorová, Petra; Strnad, Miroslav; Novák, Ondřej; Guo, G.Q.
Roč. 5, JUL 6 (2015) ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : ETHYLENE-INSENSITIVE MUTANTS * YUCCA FLAVIN MONOOXYGENASES * ARABIDOPSIS-THALIANA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.228, year: 2015
An exploration via an anonymous questionnaire of Australian public attitudes towards medical genetics and sample banking revealed the overwhelming majority views these developments with thoughtful confidence. Continued public education and awareness of these issues will allow the public to make informed decisions and enhance vigilance towards the sometimes misleading coverage in the press and media.
... discriminant power between the castor bean accesses, being the multivariate analysis efficient in this process. The castor bean accesses ACS-001 CRSP and ACS-001-MASP are promising for introduction in genetic improvement programs of this culture. Keywords: Ricinus communis L., genotype, multivariate statistics, ...
Anasagasti, Ander; Barandika, Olatz; Irigoyen, Cristina; Benitez, Bruno A; Cooper, Breanna; Cruchaga, Carlos; López de Munain, Adolfo; Ruiz-Ederra, Javier
Retinitis Pigmentosa (RP) involves a group of genetically determined retinal diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cone cells. Most cases of RP are monogenic, with more than 80 associated genes identified so far. The high number of genes and variants involved in RP, among other factors, is making the molecular characterization of RP a real challenge for many patients. Although HRM has been used for the analysis of isolated variants or single RP genes, as far as we are concerned, this is the first study that uses HRM analysis for a high-throughput screening of several RP genes. Our main goal was to test the suitability of HRM analysis as a genetic screening technique in RP, and to compare its performance with two of the most widely used NGS platforms, Illumina and PGM-Ion Torrent technologies. RP patients (n = 96) were clinically diagnosed at the Ophthalmology Department of Donostia University Hospital, Spain. We analyzed a total of 16 RP genes that meet the following inclusion criteria: 1) size: genes with transcripts of less than 4 kb; 2) number of exons: genes with up to 22 exons; and 3) prevalence: genes reported to account for, at least, 0.4% of total RP cases worldwide. For comparison purposes, RHO gene was also sequenced with Illumina (GAII; Illumina), Ion semiconductor technologies (PGM; Life Technologies) and Sanger sequencing (ABI 3130xl platform; Applied Biosystems). Detected variants were confirmed in all cases by Sanger sequencing and tested for co-segregation in the family of affected probands. We identified a total of 65 genetic variants, 15 of which (23%) were novel, in 49 out of 96 patients. Among them, 14 (4 novel) are probable disease-causing genetic variants in 7 RP genes, affecting 15 patients. Our HRM analysis-based study, proved to be a cost-effective and rapid method that provides an accurate identification of genetic RP variants. This approach is effective for
This paper describes two studies about the determinants of attitudes to pre-implantation genetic screening in a multicultural sample of medical students from the United States. Sample sizes were 292 in study 1 and 1464 in study 2. Attitudes were of an undifferentiated nature, but respondents did make a major distinction between use for disease prevention and use for enhancement. No strong distinctions were made between embryo selection and germ line gene manipulations, and between somatic gene therapy and germ line gene manipulations. Religiosity was negatively associated with acceptance of "designer baby" technology for Christians and Muslims but not Hindus. However, the strongest and most consistent influence was an apparently moralistic stance against active and aggressive interference with natural processes in general. Trust in individuals and institutions was unrelated to acceptance of the technology, indicating that fear of abuse by irresponsible individuals and corporations is not an important determinant of opposition.
Kauffman, Tia L; Wilfond, Benjamin S; Jarvik, Gail P; Leo, Michael C; Lynch, Frances L; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O; Goddard, Katrina A B
Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results are placed into the medical record for use by healthcare providers. Through quantitative and qualitative measures, including baseline and post result disclosure surveys, post result disclosure interviews, 1-2year follow-up interviews, and team journaling, we are obtaining data about the clinical and personal utility of genomic carrier screening in this population. Key outcomes include the number of reportable carrier and additional findings, and the comparative cost, utilization, and psychosocial impacts of usual care vs. genomic carrier screening. As the study progresses, we will compare the costs of genome sequencing and usual care as well as the cost of screening, pattern of use of genetic or mental health counseling services, number of outpatient visits, and total healthcare costs. This project includes novel investigation into human reactions and responses from would-be parents who are learning information that could both affect a future pregnancy and their own health. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.) [de
Shraga, Roman; Yarnall, Sarah; Elango, Sonya; Manoharan, Arun; Rodriguez, Sally Ann; Bristow, Sara L; Kumar, Neha; Niknazar, Mohammad; Hoffman, David; Ghadir, Shahin; Vassena, Rita; Chen, Serena H; Hershlag, Avner; Grifo, Jamie; Puig, Oscar
Current professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance. We identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity. Our analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.
Full Text Available Abstract Background Multiple endocrine neoplasia type 2 is an autosomal dominant disorder. MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism; MEN 2B by medullary thyroid carcinoma, pheochromocytoma and characteristic stigmata. Activating germline mutations of the RET proto oncogene are responsible for this hereditary syndrome. Codon 634 mutations are the most common mutations occurring in MEN 2A families whereas a specific mutation at codon 918 is observed in the great majority of MEN 2B families. Analysis of these codons will provide a final diagnosis in the great majority of affected families making unnecessary further studies. To specifically study the codons 634 and 918 we used a minisequencing method as an alternative method to complete sequencing. Results Using this mutation detection method we were able to reproduce in all cases, representative of 7 families, the information previously obtained by direct sequencing of PCR products. Depending on the number of primers used in the minisequencing reaction, we were able to interrogate either only one nucleotide of the target codon or the three nucleotides simultaneously. Conclusions This technique appears as a simple, rapid and efficient method for genetic screening of MEN 2 families. It can be utilized to seek for unknown mutations at specific codons or to screen for previously identified mutations and is therefore of interest to study index cases or individuals at risk. Results suggest that complete sequencing is unnecessary.
Full Text Available Genetic tests frequently produce more information than is initially expected. Several documents have addressed this issue and offer suggestions regarding how this information should be managed and, in particular, concerning the expedience of revealing (or not revealing it to the persons concerned. While the approaches to the management of these incidental findings (IFs vary, it is usually recommended that the information be disclosed if there is confirmed clinical utility and the possibility of treatment or prevention. However, this leaves unsolved some fundamental issues such as the different ways of interpreting "clinical utility", countless sources of uncertainty and varying ways of defining the notion of "incidental". Guidelines and other reference documents can offer indications to those responsible for managing IFs but should not be allowed to relieve researchers and healthcare professionals of their responsibilities.
RESEARCH NOTE. Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary .... on samples from the HMO patient's parents in an attempt to establish .... Intragenic deletions involving single or multiple EXT1 or. EXT2 exons are ...
Molecular genetic studies on obligate anaerobic bacteria have lagged behind similar studies in aerobes. However, the current interest in biotechnology, the involvement of anaerobes in disease and the emergence of antibioticresistant strains have focused attention on the genetics of anaerobes. This article reviews molecular genetic studies in Bacteroides spp., Clostridium spp. and methanogens. Certain genetic systems in some anaerobes differ from those in aerobes and illustrate the genetic diversity among bacteria
Hubbard, R; Henifin, M S
Genetic screening programs are based on assumptions and values that reflect the history of racial and social eugenics in the United States and Europe. They stigmatize individuals by shifting the focus from social, economic, and political decisions that affect the health of prospective parents, newborns, and workers to "bad genes," that is, intrapersonal factors that are given the status of "causes" of disease. Prenatal screening, at best, can help the relatively few individuals who know that their future children are at risk for a particular inherited disease or disability; it has little positive value for the average person. Workplace genetic screening has not been shown to reduce occupational disease, but it has led to employment discrimination and has drawn attention away from controlling exposures to toxic chemicals in the workplace.
Genetic association studies explore the association between genetic polymorphisms and a certain trait, disease or predisposition to disease. It has long been acknowledged that many genetic association studies fail to replicate their initial positive findings. This raises concern about the methodological quality of these reports. Case-control genetic association studies often suffer from various methodological flaws in study design and data analysis, and are often reported poorly. Flawed methodology and poor reporting leads to distorted results and incorrect conclusions. Many journals have adopted guidelines for reporting genetic association studies. In this review, some major methodological determinants of genetic association studies will be discussed.
Full Text Available Somatic cell genetics is a powerful approach for unraveling the regulatory mechanism of cholesterol metabolism. However, it is difficult to identify the mutant gene(s due to cells are usually mutagenized chemically or physically. To identify important genes controlling cholesterol biosynthesis, an unbiased forward genetics approach named validation-based insertional mutagenesis (VBIM system was used to isolate and characterize the 25-hydroxycholesterol (25-HC-resistant and SR-12813-resistant mutants. Here we report that five mutant cell lines were isolated. Among which, four sterol-resistant mutants either contain a truncated NH2-terminal domain of sterol regulatory element-binding protein (SREBP-2 terminating at amino acids (aa 400, or harbor an overexpressed SREBP cleavage-activating protein (SCAP. Besides, one SR-12813 resistant mutant was identified to contain a truncated COOH-terminal catalytic domain of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase. This study demonstrates that the VBIM system can be a powerful tool to screen novel regulatory genes in cholesterol biosynthesis.
Koutsis, G; Karadima, G; Pandraud, A; Sweeney, M G; Paudel, R; Houlden, H; Wood, N W; Panas, M
Huntington’s disease (HD) is an autosomal dominant disorder characterized by a triad of chorea, psychiatric disturbance and cognitive decline. Around 1% of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies. Genetic diseases that can present as HD phenocopies include HD-like syndromes such as HDL1, HDL2 and HDL4 (SCA17), some spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes formutations causing HDL2, SCA17, SCA1, SCA2, SCA3,SCA8, SCA12 and DRPLA. Fifteen patients (71%) had a positive family history. We identified one patient (4.8% of the total cohort) with an expansion of 81 combined CTA/CTG repeats at the SCA8 locus. This falls within what is believed to be the high-penetrance allele range. In addition to the classic HD triad, the patient had features of dystonia and oculomotor apraxia. There were no cases of HDL2, SCA17, SCA1, SCA2, SCA3, SCA12 or DRPLA. Given the controversy surrounding the SCA8 expansion, the present finding may be incidental. However, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions. The absence of any other mutations in our cohort is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients.
Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn
Pressman, Sigal; Reinke, Catherine A; Wang, Xiaohong; Carthew, Richard W
A central goal of microRNA biology is to elucidate the genetic program of miRNA function and regulation. However, relatively few of the effectors that execute miRNA repression have been identified. Because such genes may function in many developmental processes, mutations in them are expected to be pleiotropic and thus are discarded in most standard genetic screens. Here, we describe a systematic screen designed to identify all Drosophila genes in ∼40% of the genome that function in the miRNA pathway. To identify potentially pleiotropic genes, the screen analyzed clones of homozygous mutant cells in heterozygous animals. We identified 45 mutations representing 24 genes, and we molecularly characterized 9 genes. These include 4 previously known genes that encode core components of the miRNA pathway, including Drosha, Pasha, Dicer-1, and Ago1. The rest are new genes that function through chromatin remodeling, signaling, and mRNA decapping. The results suggest genetic screens that use clonal analysis can elucidate the miRNA program and that ∼100 genes are required to execute the miRNA program.
Choi, Su-Lim; Rha, Eugene; Lee, Sang Jun; Kim, Haseong; Kwon, Kilkoang; Jeong, Young-Su; Rhee, Young Ha; Song, Jae Jun; Kim, Hak-Sung; Lee, Seung-Goo
Large-scale screening of enzyme libraries is essential for the development of cost-effective biological processes, which will be indispensable for the production of sustainable biobased chemicals. Here, we introduce a genetic circuit termed the Genetic Enzyme Screening System that is highly useful for high-throughput enzyme screening from diverse microbial metagenomes. The circuit consists of two AND logics. The first AND logic, the two inputs of which are the target enzyme and its substrate, is responsible for the accumulation of a phenol compound in cell. Then, the phenol compound and its inducible transcription factor, whose activation turns on the expression of a reporter gene, interact in the other logic gate. We confirmed that an individual cell harboring this genetic circuit can present approximately a 100-fold higher cellular fluorescence than the negative control and can be easily quantified by flow cytometry depending on the amounts of phenolic derivatives. The high sensitivity of the genetic circuit enables the rapid discovery of novel enzymes from metagenomic libraries, even for genes that show marginal activities in a host system. The crucial feature of this approach is that this single system can be used to screen a variety of enzymes that produce a phenol compound from respective synthetic phenyl-substrates, including cellulase, lipase, alkaline phosphatase, tyrosine phenol-lyase, and methyl parathion hydrolase. Consequently, the highly sensitive and quantitative nature of this genetic circuit along with flow cytometry techniques could provide a widely applicable toolkit for discovering and engineering novel enzymes at a single cell level.
Waiblinger, Hans-Ulrich; Grohmann, Lutz; Mankertz, Joachim; Engelbert, Dirk; Pietsch, Klaus
In routine analysis, screening methods based on real-time PCR are most commonly used for the detection of genetically modified (GM) plant material in food and feed. In this paper, it is shown that the combination of five DNA target sequences can be used as a universal screening approach for at least 81 GM plant events authorised or unauthorised for placing on the market and described in publicly available databases. Except for maize event LY038, soybean events DP-305423 and BPS-CV127-9 and cotton event 281-24-236 x 3006-210-23, at least one of the five genetic elements has been inserted in these GM plants and is targeted by this screening approach. For the detection of these sequences, fully validated real-time PCR methods have been selected. A screening table is presented that describes the presence or absence of the target sequences for most of the listed GM plants. These data have been verified either theoretically according to available databases or experimentally using available reference materials. The screening table will be updated regularly by a network of German enforcement laboratories.
Ramos, Laia; Daina, Gemma; Del Rey, Javier; Ribas-Maynou, Jordi; Fernández-Encinas, Alba; Martinez-Passarell, Olga; Boada, Montserrat; Benet, Jordi; Navarro, Joaquima
To assess whether preimplantation genetic screening can successfully identify cytogenetically normal embryos in couples carrying balanced chromosome rearrangements in addition to increased sperm DNA fragmentation. Comprehensive preimplantation genetic screening was performed on three couples carrying chromosome rearrangements. Sperm DNA fragmentation was assessed for each patient. Academic center. One couple with the male partner carrying a chromosome 2 pericentric inversion and two couples with the male partners carrying a Robertsonian translocation (13:14 and 14:21, respectively). A single blastomere from each of the 18 cleavage-stage embryos obtained was analysed by metaphase comparative genomic hybridization. Single- and double-strand sperm DNA fragmentation was determined by the alkaline and neutral Comet assays. Single- and double-strand sperm DNA fragmentation values and incidence of chromosome imbalances in the blastomeres were analyzed. The obtained values of single-strand sperm DNA fragmentation were between 47% and 59%, and the double-strand sperm DNA fragmentation values were between 43% and 54%. No euploid embryos were observed in the couple showing the highest single-strand sperm DNA fragmentation. However, euploid embryos were observed in the other two couples: embryo transfer was performed, and pregnancy was achieved by the couple showing the lowest sperm DNA fragmentation values. Preimplantation genetic screening enables the detection of euploid embryos in couples affected by balanced chromosome rearrangements and increased sperm DNA fragmentation. Even though sperm DNA fragmentation may potentially have clinical consequences on fertility, comprehensive preimplantation genetic screening allows for the identification and transfer of euploid embryos. Copyright © 2015. Published by Elsevier Inc.
Hendrickx, Gretl; Boudin, Eveline; Steenackers, Ellen
A role for WNT4 and WNT5B in bone metabolism was indicated by genome-wide association studies (GWAS) and a Wnt4 knockout mouse model. The aim of this study was therefore to replicate and further investigate the causality between genetic variation in WNT4 and WNT5B and deviating bone mineral density...... (BMD) values. A WNT4 and WNT5B mutation screening was performed in patients with craniotubular hyperostosis using Sanger sequencing. Here, no putative causal mutations were detected. Moreover, a high and low BMD cohort was selected from the Odense Androgen Study population for re-sequencing. In WNT4 we...
Sapiro, Anne L; Ihry, Robert J; Buhr, Derek L; Konieczko, Kevin M; Ives, Sarah M; Engstrom, Anna K; Wleklinski, Nicholas P; Kopish, Kristin J; Bashirullah, Arash
Mutagenesis screens are a staple of classical genetics. Chemical-induced mutations, however, are often difficult and time-consuming to identify. Here, we report that recombination analysis with pairs of dominant visible markers provides a rapid and reliable strategy to map mutations in Drosophila melanogaster. This method requires only two generations and a total of six crosses in vials to estimate the genetic map position of the responsible lesion with high accuracy. This genetic map position can then be reliably used to identify the mutated gene through complementation testing with an average of nine deficiencies and Sanger sequencing. We have used this approach to successfully map a collection of mutations from an ethyl methanesulfonate-based mutagenesis screen on the third chromosome. We propose that this method also may be used in conjunction with whole-genome sequencing, particularly when multiple independent alleles of the mutated locus are not available. By facilitating the rapid identification of mutated genes, our mapping strategy removes a primary obstacle to the widespread use of powerful chemical mutagenesis screens to understand fundamental biological phenomena.
Ring, Kari L; Garcia, Christine; Thomas, Martha H; Modesitt, Susan C
The world of hereditary cancers has seen exponential growth in recent years. While hereditary breast and ovarian cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate risk-reduction strategies. Given the speed of information, it is imperative to involve cancer genetics experts when counseling these patients. In addition, coordination of screening and care in conjunction with specialty high-risk clinics, if available, allows for patients to have centralized management for multiple cancer risks under the guidance of physicians with experience counseling these patients. The objective of this review is to present the current literature regarding genetic mutations associated with gynecologic malignancies as well to propose screening and risk-reduction options for these high-risk patients. Copyright © 2017 Elsevier Inc. All rights reserved.
Ossa, Diego F; Towse, Adrian
The potential use of genetic tests in insurance has raised concerns about discrimination and individuals losing access to health care either because of refusals to test for treatable diseases, or because test-positives cannot afford premiums. Governments have so far largely sought to restrict the use of genetic information by insurance companies. To date the number of tests available with significant actuarial value is limited. However, this is likely to change, raising more clearly the question as to whether the social costs of adverse selection outweigh the social costs of individuals not accessing health care for fear of the consequences of test information being used in insurance markets. In this contribution we set out the policy context and model the potential trade-offs between the losses faced by insurers from adverse selection by insurees (which will increase premiums reducing consumer welfare) and the detrimental health effects that may result from persons refusing to undergo tests that could identify treatable health conditions. It argues that the optimal public policy on genetic testing should reflect overall societal benefit, taking account of these trade-offs. Based on our model, the factors that influence the outcome include: the size of and value attached to the health gains from treatment; deterrent effects of a disclosure requirement on testing for health reasons; incidence of the disease; propensity of test-positives to adverse select; policy value adverse selectors buy in a non-disclosure environment; and price elasticity of demand for insurance. Our illustrative model can be used as a benchmark for developing other scenarios or incorporating real data in order to address the impact of different policies on disclosure and requirement to test.
Scholtens, Ingrid; Laurensse, Emile; Molenaar, Bonnie; Zaaijer, Stephanie; Gaballo, Heidi; Boleij, Peter; Bak, Arno; Kok, Esther
Nowadays most animal feed products imported into Europe have a GMO (genetically modified organism) label. This means that they contain European Union (EU)-authorized GMOs. For enforcement of these labeling requirements, it is necessary, with the rising number of EU-authorized GMOs, to perform an increasing number of analyses. In addition to this, it is necessary to test products for the potential presence of EU-unauthorized GMOs. Analysis for EU-authorized and -unauthorized GMOs in animal feed has thus become laborious and expensive. Initial screening steps may reduce the number of GMO identification methods that need to be applied, but with the increasing diversity also screening with GMO elements has become more complex. For the present study, the application of an informative detailed 24-element screening and subsequent identification strategy was applied in 50 animal feed samples. Almost all feed samples were labeled as containing GMO-derived materials. The main goal of the study was therefore to investigate if a detailed screening strategy would reduce the number of subsequent identification analyses. An additional goal was to test the samples in this way for the potential presence of EU-unauthorized GMOs. Finally, to test the robustness of the approach, eight of the samples were tested in a concise interlaboratory study. No significant differences were found between the results of the two laboratories.
Palmer, K T; Poole, J; Rawbone, R G; Coggon, D
Tests of genotype may enable workers at unusual risk of future ill-health to be identified. Using them to select for employment, however, entails gains and losses to employers and employees. Ensuring a fair balance between the rights and obligations of each group requires a value judgement, but the advantages and disadvantages to interested parties must first be quantified in a meaningful way. The purposes of pre-employment screening are reviewed, and several simple measures relevant to the separate interests of employers and job applicants proposed-number screened to prevent a single adverse outcome; number excluded to prevent a case; expected incidence of the adverse outcome in those excluded; and preventable fraction. The derivation of these measures is illustrated, and the factors that influence them (the prevalence of the prognostic trait, the relative risk that it carries for an adverse outcome, and the overall incidence of disease) are related algebraically and graphically, to aid judgement on the utility of screening under different circumstances. In sensitive areas such as genetic testing the onus should be on the employer to justify plans for pre-placement screening. Several quantitative measures can be used to inform the ethical and economic debate about screening and to evaluate alternative strategies for prevention.
Pei, Wuhong; Xu, Lisha; Huang, Sunny C; Pettie, Kade; Idol, Jennifer; Rissone, Alberto; Jimenez, Erin; Sinclair, Jason W; Slevin, Claire; Varshney, Gaurav K; Jones, MaryPat; Carrington, Blake; Bishop, Kevin; Huang, Haigen; Sood, Raman; Lin, Shuo; Burgess, Shawn M
Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury. To understand the mechanism of hair cell regeneration and its association with regeneration of other tissues, we performed a guided mutagenesis screen using zebrafish lateral line hair cells as a screening platform to identify genes that are essential for hair cell regeneration, and further investigated how genes essential for hair cell regeneration were involved in the regeneration of other tissues. We created genetic mutations either by retroviral insertion or CRISPR/Cas9 approaches, and developed a high-throughput screening pipeline for analyzing hair cell development and regeneration. We screened 254 gene mutations and identified 7 genes specifically affecting hair cell regeneration. These hair cell regeneration genes fell into distinct and somewhat surprising functional categories. By examining the regeneration of caudal fin and liver, we found these hair cell regeneration genes often also affected other types of tissue regeneration. Therefore, our results demonstrate guided screening is an effective approach to discover regeneration candidates, and hair cell regeneration is associated with other tissue regeneration.
Eijzenga, W; Bleiker, E M A; Hahn, D E E; Kluijt, I; Sidharta, G N; Gundy, C; Aaronson, N K
Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific psychosocial problems related to cancer genetic counseling. We adopted the European Organisation for Research and Treatment of Cancer Quality of Life Group guidelines to develop the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, a 26-item questionnaire organized into six problem domains: genetics, practical issues, family, living with cancer, emotions, and children. The Distress Thermometer and a question per domain on the perceived need for extra psychosocial services were included as well. We administered the questionnaire and the Hospital Anxiety and Depression Scale to 127 counselees at the time of genetic counseling and 3 weeks after DNA test disclosure. As a gold standard to evaluate the screening properties of the questionnaire, participants underwent a semi-structured interview with an experienced social worker who assessed the presence and severity of problems per domain. A cutoff score representing responses of 'quite a bit' or 'very much' to one or more items within a given problem domain yielded moderate to high sensitivity across domains. A cutoff of 4 on the Distress Thermometer yielded high sensitivity. The questions regarding the perceived need for extra psychosocial services yielded high specificity and negative predictive values. The Psychosocial Aspects of Hereditary Cancer questionnaire in combination with the Distress Thermometer can be used as a first-line screener for psychosocial problems within the cancer genetic counseling setting. Copyright © 2014 John Wiley & Sons, Ltd.
Middleton, Anna; Patch, Chris; Wiggins, Jennifer; Barnes, Kathy; Crawford, Gill; Benjamin, Caroline; Bruce, Anita
The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest ‘opportunistic genomic screening' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), w...
Scicali, R; Di Pino, A; Platania, R; Purrazzo, G; Ferrara, V; Giannone, A; Urbano, F; Filippello, A; Rapisarda, V; Farruggia, E; Piro, S; Rabuazzo, A M; Purrello, F
Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT). We screened 1575 lipid profiles and included for genetic analysis adults with a low-density lipoprotein (LDL) cholesterol >190 mg/dL and triglycerides 160 mg/dL and triglycerides 8 it was 100%. Mean IMT was higher in FH patients compared to non FH (0.73 [0.61-0.83] vs 0.71 [0.60-0.75] mm, p 190 mg/dL and corneal arcus (p < 0.01 and p < 0.001, respectively). A hospital screening was useful to detect FH subjects with increased atherosclerosis. Also, next-generation sequencing was able to detect new FH mutations. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Ginsburg, Elizabeth S; Baker, Valerie L; Racowsky, Catherine; Wantman, Ethan; Goldfarb, James; Stern, Judy E
To comprehensively report Society for Assisted Reproductive Technology (SART) member program usage of preimplantation genetic testing (PGT), preimplantation genetic diagnosis (PGD) for diagnosis of specific conditions, and preimplantation genetic screening for aneuploidy (PGS). Retrospective study. United States SART cohort data. Women undergoing a PGT cycle in which at least one embryo underwent biopsy. PGT. PGT use, indications, and delivery rates. Of 190,260 fresh, nondonor assisted reproductive technology (ART) cycles reported to SART CORS in 2007-2008, 8,337 included PGT. Of 6,971 cycles with a defined indication, 1,382 cycles were for genetic diagnosis, 3,645 for aneuploidy screening (PGS), 527 for translocation, and 1,417 for elective sex election. Although the total number of fresh, autologous cycles increased by 3.6% from 2007 to 2008, the percentage of cycles with PGT decreased by 5.8% (4,293 in 2007 and 4,044 in 2008). As a percentage of fresh, nondonor ART cycles, use dropped from 4.6% (4,293/93,433) in 2007 to 4.2% (4,044/96,827) in 2008. The primary indication for PGT was PGS: cycles performed for this indication decreased (-8.0%). PGD use for single-gene defects (+3.2%), elective sex selection (+5.3%), and translocation analysis (+0.5%) increased. PGT usage varied significantly by geographical region. PGT usage in the United States decreased between 2007 and 2008 owing to a decrease in PGS. Use of elective sex selection increased. High transfer cancellation rates correlated with reduced live-birth rates for some PGT indications. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Sutherland, Sharon; Farrell, Ruth M; Lockwood, Charles
The State of Ohio is implementing an episode-based payment model for perinatal care. All costs of care will be tabulated for each live birth and assigned to the delivering provider, creating a three-tiered model for reimbursement for care. Providers will be reimbursed as usual for care that is average in cost and quality, while instituting rewards or penalties for those outside the expected range in either domain. There are few exclusions, and all methods of genetic screening and diagnostic testing are included in the episode cost calculation as proposed. Prenatal ultrasonography, genetic screening, and diagnostic testing are critical components of the delivery of high-quality, evidence-based prenatal care. These tests provide pregnant women with key information about the pregnancy, which, in turn, allows them to work closely with their health care provider to determine optimal prenatal care. The concepts of informed consent and decision-making, cornerstones of the ethical practice of medicine, are founded on the principles of autonomy and respect for persons. These principles recognize that patients' rights to make choices and take actions are based on their personal beliefs and values. Given the personal nature of such decisions, it is critical that patients have unbarred access to prenatal genetic tests if they elect to use them as part of their prenatal care. The proposed restructuring of reimbursement creates a clear conflict between patient autonomy and physician financial incentives.
Full Text Available Amyotrophic lateral sclerosis (ALS is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs. We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A logical consequence of this is that loss-of-function mutations in G4C2-binding partners might contribute to ALS pathogenesis independently of and/or synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA encoding either RNA-binding proteins or known ALS genes (n = 274 genes was performed in ALS patients to identify rare deleterious genetic variants and explore genotype-phenotype relationships. Genomic DNA was extracted from 103 ALS patients including 42 familial ALS patients and 61 young-onset (average age of onset 41 years sporadic ALS patients; patients were chosen to maximize the probability of identifying genetic causes of ALS. Thirteen patients carried a G4C2-repeat expansion of C9ORF72. We identified 42 patients with rare deleterious variants; 6 patients carried more than one variant. Twelve mutations were discovered in known ALS genes which served as a validation of our strategy. Rare deleterious variants in RNA-binding proteins were significantly enriched in ALS patients compared to control frequencies (p = 5.31E-18. Nineteen patients featured at least one variant in a RNA-binding protein containing a PrLD. The number of variants per patient correlated with rate of disease progression (t-test, p = 0.033. We identified eighteen patients with a single variant in a G4C2-repeat binding protein. Patients with a G4C2-binding protein variant in combination with a C9ORF72 expansion had a significantly faster disease course (t-test, p = 0.025. Our data are
Middelburg, Karin J.; van der Heide, Maaike; Houtzager, Bregje; Pereboom, Marjolein; Fidler, Vaclav; Bos, Arend F.; Kok, Joke; Hadders-Algra, Mijna
Objective: To evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcomes in children. Design: Prospective, assessor-blinded, follow-up study of children born to women randomly assigned to in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) with or
Shailaja Gada Saxena
Full Text Available Context: There is a high incidence of numerical chromosomal aberration in couples with repeated in vitro fertilization (IVF failure, advanced maternal age, repeated unexplained abortions, severe male factor infertility and unexplained infertility. Pre-implantation genetic screening (PGS, a variant of pre-implantation genetic diagnosis, screens numerical chromosomal aberrations in couples with normal karyotype, experiencing poor reproductive outcome. The present study includes the results of the initial pilot study on 9 couples who underwent 10 PGS cycles. Aim: The aim of the present study was to evaluate the beneficial effects of PGS in couples with poor reproductive outcome. Settings and Design: Data of initial 9 couples who underwent 10 PGS for various indications was evaluated. Subjects and Methods: Blastomere biopsy was performed on cleavage stage embryos and subjected to two round fluorescence in situ hybridization (FISH testing for chromosomes 13, 18, 21, X and Y as a two-step procedure. Results: Six of the 9 couples (10 PGS cycles conceived, including a twin pregnancy in a couple with male factor infertility, singleton pregnancies in a couple with secondary infertility, in three couples with adverse obstetric outcome in earlier pregnancies and in one couple with repeated IVF failure. Conclusion: In the absence of availability of array-comparative genomic hybridization in diagnostic clinical scenario for PGS and promising results with FISH based PGS as evident from the current pilot study, it is imperative to offer the best available services in the present scenario for better pregnancy outcome for patients.
Mitchell, M X
In the years following World War II, and increasingly during the 1960s and 1970s, professional scientific societies developed internal sub-committees to address the social implications of their scientific expertise (Moore, Disrupting Science: Social Movements, American Scientists, and the Politics of the Military, 1945-1975. Princeton: Princeton University Press, 2008). This article explores the early years of one such committee, the American Society of Human Genetics' "Social Issues Committee," founded in 1967. Although the committee's name might suggest it was founded to increase the ASHG's public and policy engagement, exploration of the committee's early years reveals a more complicated reality. Affronted by legislators' recent unwillingness to seek the expert advice of human geneticists before adopting widespread neonatal screening programs for phenylketonuria (PKU), and feeling pressed to establish their relevance in an increasingly resource-scarce funding environment, committee members sought to increase the discipline's expert authority. Painfully aware of controversy over abortion rights and haunted by the taint of the discipline's eugenic past, however, the committee proceeded with great caution. Seeking to harness interest in and assert professional control over emerging techniques of genetic diagnosis, the committee strove to protect the society's image by relegating ethical and policy questions about their use to the individual consciences of member scientists. It was not until 1973, after the committee's modest success in organizing support for a retrospective public health study of PKU screening and following the legalization of abortion on demand, that the committee decided to take a more publicly engaged stance.
Doucette, Jaimee; Zhao, Ziyan; Geyer, Rory J; Barra, Melanie M; Balunas, Marcy J; Zweifach, Adam
Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)-activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections. © 2016 Society for Laboratory Automation and Screening.
Loosli, F; Köster, R W; Carl, M; Kühnlein, R; Henrich, T; Mücke, M; Krone, A; Wittbrodt, J
In a pilot screen, we assayed the efficiency of ethylnitrosourea (ENU) as a chemical mutagen to induce mutations that lead to early embryonic and larval lethal phenotypes in the Japanese medaka fish, Oryzias latipes. ENU acts as a very efficient mutagen inducing mutations at high rates in germ cells. Three repeated treatments of male fish in 3 mM ENU for 1 h results in locus specific mutation rates of 1.1-1.95 x10(-3). Mutagenized males were outcrossed to wild type females and the F1 offspring was used to establish F2 families. F2 siblings were intercrossed and the F3 progeny was scored 24, 48 and 72 h after fertilization for morphological alterations affecting eye development. The presented mutant phenotypes were identified using morphological criteria and occur during early developmental stages of medaka. They are stably inherited in a Mendelian fashion. The high efficiency of ENU to induce mutations in this pilot screen indicates that chemical mutagenesis and screening for morphologically visible phenotypes in medaka fish allows the genetic analysis of specific aspects of vertebrate development complementing the screens performed in other vertebrate model systems.
Full Text Available modified crops which brought up a controversy on the safety usage of genetically modified organisms (GMOs. It has been implemented globally that all GMO products and its derived ingredients should have regulations on the usage and labelling. Thus, it is necessary to develop methods that allow rapid screening of GMO products to comply with the regulations. This study employed a reliable and flexible multiplex polymerase chain reaction (PCR method for the rapid detection of transgenic elements in genetically modified soy and maize along with the soybean LECTIN gene and maize ZEIN gene respectively. The selected four common transgenic elements were 35S promoter (35S; Agrobacterium tumefaciens nopaline synthase terminator (NOS; 5-enolypyruvylshikimate-3-phosphate synthase (epsps gene; and Cry1Ab delta-endotoxin (cry1Ab gene. Optimization of the multiplex PCR methods were carried out by using 1% Roundup ReadyTM Soybean (RRS as the certified reference material for soybean that produced fourplex PCR method detecting 35S promoter, NOS terminator, epsps gene and soybean LECTIN gene and by using 1% MON810 as the certified reference material for maize that produced triplex PCR method detecting 35S promoter, cry1Ab gene and maize ZEIN gene prior to screening of the GMO traits in various food products and animal feeds. 1/9 (11.1% of the animal feed contained maize and 1/15 (6.7% of the soybean food products showed positive results for the detection of GMO transgenic gene. None of the maize food products showed positive results for GMO transgenic gene. In total, approximately 4% of the food products and animal feed were positive as GMO. This indicated GMOs have not widely entered the food chain. However, it is necessary to have an appropriate screening method due to GMOs’ unknown potential risk to humans and to animals. This rapid screening method will provide leverage in terms of being economically wise, time saving and reliable.
S. S. Deryabina
Full Text Available The article considers philosophical questions of neonatal screening technology. The main focus is on ethical and methodological issues that inevitably arise when expanding the number of scanned nosologies and applying genetic research methods. Questions concerning the existing discrepancy between technical capacity and the practical level of healthcare delivery and the probabilistic nature of results obtained by molecular testing are analyzed in terms of methodology. Access to information about the DNA-testing of newborns and the linkage between neonatal screening and prenatal diagnostics are among the most topical ethical problems raised within this article. One of the purposes of this article is to draw the attention of the public — especially it concerns current and prospective parents and volunteer organizations — to these contemporary problems.
Kaufman, Thomas C
The purpose of this chapter in FlyBook is to acquaint the reader with the Drosophila genome and the ways in which it can be altered by mutation. Much of what follows will be familiar to the experienced Fly Pusher but hopefully will be useful to those just entering the field and are thus unfamiliar with the genome, the history of how it has been and can be altered, and the consequences of those alterations. I will begin with the structure, content, and organization of the genome, followed by the kinds of structural alterations (karyotypic aberrations), how they affect the behavior of chromosomes in meiotic cell division, and how that behavior can be used. Finally, screens for mutations as they have been performed will be discussed. There are several excellent sources of detailed information on Drosophila husbandry and screening that are recommended for those interested in further expanding their familiarity with Drosophila as a research tool and model organism. These are a book by Ralph Greenspan and a review article by John Roote and Andreas Prokop, which should be required reading for any new student entering a fly lab for the first time. Copyright © 2017 by the Genetics Society of America.
de Koning-Ward Tania F
Full Text Available Abstract The ability to analyze gene function in malaria-causing Plasmodium parasites has received a boost with a recent paper in BMC Genomics that describes a genome-wide mutagenesis system in the rodent malaria species Plasmodium berghei using the transposon piggyBac. This advance holds promise for identifying and validating new targets for intervention against malaria. But further improvements are still needed for the full power of genome-wide molecular genetic screens to be utilized in this organism. See research article: http://www.biomedcentral.com/1471-2164/12/155
Yan, Junxia; Hitomi, Toshiaki; Takenaka, Katsunobu; Kato, Masayasu; Kobayashi, Hatasu; Okuda, Hiroko; Harada, Kouji H; Koizumi, Akio
Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, leading to immediate death or severe disability. Identification of the genetic factors involved is critical for disease prevention and treatment. We aimed to identify the susceptibility genes for IAs. Exome sequencing was performed in 12 families with histories of multiple cases of IA (number of cases per family ≥3), with a total of 42 cases. Various filtering strategies were used to select the candidate variants. Replicate association studies of several candidate variants were performed in probands of 24 additional IA families and 426 sporadic IA cases. Functional analysis for the mutations was conducted. After sequencing and filtering, 78 variants were selected for the following reasons: allele frequencies of variants in 42 patients was significantly (PIA within ≥1 family; variants predicted damage to the structure or function of the protein by PolyPhen-2 (Polymorphism Phenotyping V2) and SIFT (Sorting Intolerance From Tolerant). We selected 10 variants from 9 genes (GPR63, ADAMST15, MLL2, IL10RA, PAFAH2, THBD, IL11RA, FILIP1L, and ZNF222) to form 78 candidate variants by considering commonness in families, known disease genes, or ontology association with angiogenesis. Replicate association studies revealed that only p.E133Q in ADAMTS15 was aggregated in the familial IA cases (odds ratio, 5.96; 95% confidence interval, 2.40-14.82; P=0.0001; significant after the Bonferroni correction [P=0.05/78=0.0006]). Silencing ADAMTS15 and overexpression of ADAMTS15 p.E133Q accelerated endothelial cell migration, suggesting that ADAMTS15 may have antiangiogenic activity. ADAMTS15 is a candidate gene for IAs. © 2015 American Heart Association, Inc.
Full Text Available The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF embryos. Preimplantation genetic diagnosis (PGD or screening (PGS involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future.
The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. PMID:24783200
Pers, Tune H
Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...
Rochette, Claire; Baumstarck, Karine; Canoni-Zattara, Hélène; Abdullah, Ahmad Esmaeel; Figarella-Branger, Dominique; Pertuit, Morgane; Barlier, Anne; Castinetti, Frédéric; Pacak, Karel; Metellus, Philippe; Taïeb, David
Von Hippel-Lindau (VHL) syndrome is a hereditary cancer syndrome characterized by a high risk of developing benign and malignant tumors, including central nervous system hemangioblastomas (CNS HBs). For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients. The aim of the study was to assess the psychological impact of VHL genetic testing in patients previously diagnosed with a CNS HB. From 1999 until 2015, 55 patients underwent surgery for CNS HBs. Eleven patients were already screened for VHL mutations and 3 patients deceased before the start of the study. From the remaining 42 patients, 24 were accepted to be enrolled in the study. Assessment of psychological impact of VHL genetic testing was performed by measuring anxiety levels, mood disorders, quality of life, and psychological consequences of genetic screening. Twenty-one of the enrolled 24 patients underwent VHL genetic testing and 12 patients came back for the communication of positive genetic results. The baseline psychological status did not differ between these 2 groups. Patients who attended the visit of communication of genetic results had similar anxiety levels compared to those who had not. Furthermore, they also experienced an improvement in the level of anxiety and two QoL dimension scores compared to their baseline status. In summary, there is no evidence of a negative psychosocial impact of VHL genetic testing in patients with a previous history of CNS HB. We, therefore, recommend the recall of patients who have not been previously screened.
Genetic interaction studies are a powerful approach to identify functional interactions between genes. This approach can reveal networks of regulatory hubs and connect uncharacterized genes to well-studied pathways. However, this approach has previously been limited to simple gene inactivation studies. Here, we present an orthogonal CRISPR/Cas-mediated genetic interaction approach that allows the systematic activation of one gene while simultaneously knocking out a second gene in the same cell.
Irwin, John J; Shoichet, Brian K; Mysinger, Michael M; Huang, Niu; Colizzi, Francesco; Wassam, Pascal; Cao, Yiqun
Molecular docking is the most practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCK Blaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCK Blaster recapitulates the crystal ligand pose within 2 A rmsd 50-60% of the time; inferior to an expert, but respectrable. Half the time the ligand also ranked among the top 5% of 100 physically matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2 A rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org .
Full Text Available The recent success of derivation of mammalian haploid embryonic stem cells (haESCs has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous diploidization of haESCs happens in metaphase due to mitotic slippage. Diploidization can be suppressed by small-molecule-mediated inhibition of CDK1 and ROCK. Through ROCK inhibition, we can generate haploid somatic cells of all three germ layers from haESCs, including terminally differentiated neurons. Using piggyBac transposon-based insertional mutagenesis, we generated a haploid neural cell library harboring genome-wide mutations for genetic screening. As a proof of concept, we screened for Mn2+-mediated toxicity and identified the Park2 gene. Our findings expand the applications of mouse haploid cell technology to somatic cell types and may also shed light on the mechanisms of ploidy maintenance.
Bellcross, Cecelia; Hermstad, April; Tallo, Christine; Stanislaw, Christine
Despite increased awareness of hereditary breast and ovarian cancer among clinicians and the public, many BRCA1/2 mutation carriers remain unaware of their risk status. The Breast Cancer Genetics Referral Screening Tool (B-RST™) was created and validated to easily identify individuals at increased risk for hereditary breast and ovarian cancer for referral to cancer genetics services. The purpose of this study was to revise B-RST™ to maximize sensitivity against BRCA1/2 mutation status. We analyzed pedigrees of 277 individuals who had undergone BRCA1/2 testing to determine modifications to the B-RST™ 2.0 algorithm that would maximize sensitivity for mutations, while maintaining simplicity. We used McNemar's chi-square test to compare validation measures between the revised version (3.0) and the 2.0 version. Algorithmic changes made to B-RST™ 2.0 increased the sensitivity against BRCA1/2 mutation analysis from 71.1 to 94.0% (P 3.0 demonstrates high sensitivity for BRCA1/2 mutations, yet remains a simple and quick screening tool for at-risk individuals.
Rodríguez, Sally Ann; Roter, Debra L; Castillo-Salgado, Carlos; Hooker, Gillian W; Erby, Lori H
Literacy deficits and underutilization of medical services have been linked to health disparities among minorities, and this appears especially relevant for the Latino population. Given the increasing importance of genetics, assessment of genetic health literacy may direct future efforts to better serve this vulnerable population. The current study was designed to contribute to this area by translating and validating a Spanish-language genetic health literacy measure. This was a cross-sectional study involving an interviewer-administered questionnaire. Eligible individuals were Latinos between the ages of 18 and 75 residing in Maryland, who self-reported Spanish as their primary language, recruited through convenience sampling. The genetic health literacy measure components were adapted from existing English-language measures [Erby, Roter, Larson, & Cho's (2008) Rapid Estimate of Adult Literacy in Genetics (REAL-G) and Hooker et al.'s (2014) Genetic Literacy and Comprehension]. An existing Spanish-language general health literacy measure was used to establish preliminary concurrent validity [Lee, Bender, Ruiz, & Cho's (2006) SAHLSA]. 116 individuals completed the assessment. The Spanish-language REAL-G (REAL-G-Sp) was found to correlate well with the SAHLSA (Pearson's r = .77, p validity with an existing health literacy measure in the Latino population residing in Maryland. Significant proportions of this population are predicted to have limitations in genetic health literacy, even when information is provided in Spanish.
Full Text Available The incidence of inborn errors of metabolisms (IEMs varies dramatically in different countries and regions. Expanded newborn screening for IEMs by tandem mass spectrometry (MS/MS is an efficient approach for early diagnosis and presymptomatic treatment to prevent severe permanent sequelae and death. To determine the characteristics of IEMs and IEMs-associated mutations in newborns in Jining area, China, 48,297 healthy neonates were recruited for expanded newborn screening by MS/MS. The incidence of IEMs was 1/1178 in Jining, while methylmalonic acidemia, phenylketonuria, and primary carnitine deficiency ranked the top 3 of all detected IEMs. Thirty mutations in nine IEMs-associated genes were identified in 28 confirmed cases. As 19 cases with the mutations in phenylalanine hydroxylase (PAH, solute carrier family 22 member 5 (SLC22A5, and methylmalonic aciduria (cobalamin deficiency cblC type with homocystinuria (MMACHC genes, respectively, it suggested that mutations in the PAH, SLC22A5, and MMACHC genes are the predominant causes of IEMs, leading to the high incidence of phenylketonuria, primary carnitine deficiency, and methylmalonic acidemia, respectively. Our work indicated that the overall incidence of IEMs is high and the mutations in PAH, SLC22A5, and MMACHC genes are the leading causes of IEMs in Jining area. Therefore, it is critical to increase the coverage of expanded newborn screening by MS/MS and prenatal genetic consulting in Jining area.
Fernandez, Anita G; Mis, Emily K; Lai, Allison; Mauro, Michael; Quental, Angela; Bock, Carly; Piano, Fabio
mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for nuclear envelope function and chromosome segregation in Caenorhabditis elegans. Because mel-28 is a strict maternal-effect lethal gene, its function is required in the early embryo but appears to be dispensable for larval development. We wanted to test the idea that mel-28 has postembryonic roles that are buffered by the contributions of other genes. To find genes that act coordinately with mel-28, we did an RNA interference-based genetic interaction screen using mel-28 and wild-type larvae. We screened 18,364 clones and identified 65 genes that cause sterility in mel-28 but not wild-type worms. Some of these genes encode components of the nuclear pore. In addition we identified genes involved in dynein and dynactin function, vesicle transport, and cell-matrix attachments. By screening mel-28 larvae we have bypassed the requirement for mel-28 in the embryo, uncovering pleiotropic functions for mel-28 later in development that are normally provided by other genes. This work contributes toward revealing the gene networks that underlie cellular processes and reveals roles for a maternal-effect lethal gene later in development.
Full Text Available Abstract Background Much attention has been paid to adolescents' screen time, however very few studies have examined non-screen sedentary time (NSST. This study aimed to (1 describe the magnitude and composition of screen sedentary time (SST and NSST in Australian adolescents, (2 describe the socio-demographic correlates of SST and NSST, and (3 determine whether screen time is an adequate surrogate for total sedentary behaviour in this population. Methods 2200 9-16 year old Australians provided detailed use of time data for four days. Non-screen sedentary time (NSST included time spent participating in activities expected to elicit Results Adolescents spent a mean (SD of 345 (105 minutes/day in NSST, which constituted 60% of total sedentary time. School activities contributed 42% of NSST, socialising 19%, self-care (mainly eating 16%, and passive transport 15%. Screen time and NSST showed opposite patterns in relation to key socio-demographic characteristics, including sex, age, weight status, household income, parental education and day type. Because screen time was negatively correlated with NSST (r = -0.58, and exhibited a moderate correlation (r = 0.53 with total sedentary time, screen time was only a moderately effective surrogate for total sedentary time. Conclusions To capture a complete picture of young people's sedentary time, studies should endeavour to measure both screen time and NSST.
Middleton, Anna; Patch, Chris; Wiggins, Jennifer; Barnes, Kathy; Crawford, Gill; Benjamin, Caroline; Bruce, Anita
The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest 'opportunistic genomic screening' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients.
Rogowski, W H; Grosse, S D; Meyer, E; John, J; Palmer, S
Public decision makers face demands to invest in applied research in order to accelerate the adoption of new genetic tests. However, such an investment is profitable only if the results gained from further investigations have a significant impact on health care practice. An upper limit for the value of additional information aimed at improving the basis for reimbursement decisions is given by the expected value of perfect information (EVPI). This study illustrates the significance of the concept of EVPI on the basis of a probabilistic cost-effectiveness model of screening for hereditary hemochromatosis among German men. In the present example, population-based screening can barely be recommended at threshold values of 50,000 or 100,000 Euro per life year gained and also the value of additional research which might cause this decision to be overturned is small: At the mentioned threshold values, the EVPI in the German public health care system was ca. 500,000 and 2,200,000 Euro, respectively. An analysis of EVPI by individual parameters or groups of parameters shows that additional research about adherence to preventive phlebotomy could potentially provide the highest benefit. The potential value of further research also depends on methodological assumptions regarding the decision maker's time horizon as well as on scenarios with an impact on the number of affected patients and the cost-effectiveness of screening.
Conclusion: A multidisciplinary cancer screening program should be maintained. With such a process, the aim is to reduce the morbidity and mortality of the disease without adversely affecting the health conditions of asymptomatic individuals based on the screening. Success is brought about by the combination of individual features. [Arch Clin Exp Surg 2017; 6(1.000: 23-27
Wynhoff, N.; Girault, S.E.; Fish, R.L.
A broad range of potential stabilizer materials was identified and screened for packaging spent fuel assemblies for underground storage. The screening took into consideration the thermal gradient, stress, differential thermal expansion, nuclear criticality, radiation shielding, cost, and availability. Recommended stabilizer materials for further testing include silica, quartz, mullite, zircon, bentonite, graphite, gases, lead, Zn alloys, Cu alloys, etc
Vernet, Erik; Kotzsch, Alexander; Voldborg, Bjørn
Soluble expression of proteins in a relevant form for functional and structural investigations still often remains a challenge. Although many biochemical factors are known to affect solubility, a thorough investigation of yield-limiting factors is normally not feasible in high-throughput efforts....... Here we present a screening strategy for expression of biomedically relevant proteins in Escherichia coli using a panel of six different genetic variations. These include engineered strains for rare codon supplementation, increased disulfide bond formation in the cytoplasm and novel vectors...... for secretion to the periplasm or culture medium. Combining these variants with expression construct truncations design, we report on parallel cloning and expression of more than 300 constructs representing 24 selected proteins; including full-length variants of human growth factors, interleukins and growth...
Screening in Diabetes : Candidate Gene Analysis for Diabetic Retinopathy PRINCIPAL INVESTIGATOR: Robert A. Vigersky, COL MC CONTRACTING ORGANIZATION... Diabetes Institute of the Walter Reed Health Care System Genetic Screening in Diabetes : Candidate Gene Analysis for Diabetic Retinopathy 5c. PROGRAM... diabetic neuropathy, and diabetic retinopathy . This was an observational study in which the investigators obtained DNA samples from the blood of
Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P
Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. © FASEB.
Lebensohn, Andres M; Dubey, Ramin; Neitzel, Leif R; Tacchelly-Benites, Ofelia; Yang, Eungi; Marceau, Caleb D; Davis, Eric M; Patel, Bhaven B; Bahrami-Nejad, Zahra; Travaglini, Kyle J; Ahmed, Yashi; Lee, Ethan; Carette, Jan E; Rohatgi, Rajat
The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway. These include a requirement for the transcription factor AP-4, a role for the DAX domain of AXIN2 in controlling β-catenin transcriptional activity, a contribution of glycophosphatidylinositol anchor biosynthesis and glypicans to R-spondin-potentiated WNT signaling, and two different mechanisms that regulate signaling when distinct components of the β-catenin destruction complex are lost. The conceptual and methodological framework we describe should enable the comprehensive understanding of other signaling systems. DOI: http://dx.doi.org/10.7554/eLife.21459.001 PMID:27996937
Full Text Available Seong Soo An,1,* Sun Ah Park,2,* Eva Bagyinszky,1 Sun Oh Bae,1 Yoon-Jeong Kim,2 Ji Young Im,2 Kyung Won Park,3 Kee Hyung Park,4 Eun-Joo Kim,5 Jee Hyang Jeong,6 Jong Hun Kim,7 Hyun Jeong Han,8 Seong Hye Choi,9 SangYun Kim10 1Department of Bionano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Dong-A University College of Medicine and Institute of Convergence Bio-Health, Busan, 4Department of Neurology, Gachon University Gil Medical Center, Incheon, 5Department of Neurology, Pusan National University Hospital, Busan, 6Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul, 7Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, 8Department of Neurology, Myongii Hospital, Goyang, 9Department of Neurology, Inha University School of Medicine, Incheon, 10Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: Early-onset Alzheimer’s disease (EOAD has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD. The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD
Takabatake, Reona; Koiwa, Tomohiro; Kasahara, Masaki; Takashima, Kaori; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Oguchi, Taichi; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi
To reduce the cost and time required to routinely perform the genetically modified organism (GMO) test, we developed a duplex quantitative real-time PCR method for a screening analysis simultaneously targeting an event-specific segment for GA21 and Cauliflower Mosaic Virus 35S promoter (P35S) segment [Oguchi et al., J. Food Hyg. Soc. Japan, 50, 117-125 (2009)]. To confirm the validity of the method, an interlaboratory collaborative study was conducted. In the collaborative study, conversion factors (Cfs), which are required to calculate the GMO amount (%), were first determined for two real-time PCR instruments, the ABI PRISM 7900HT and the ABI PRISM 7500. A blind test was then conducted. The limit of quantitation for both GA21 and P35S was estimated to be 0.5% or less. The trueness and precision were evaluated as the bias and reproducibility of the relative standard deviation (RSD(R)). The determined bias and RSD(R) were each less than 25%. We believe the developed method would be useful for the practical screening analysis of GM maize.
Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang
Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.
Jul 3, 2006 ... The success of most crop improvement programs largely depends upon the genetic variability and the heritability of desirable traits. The magnitude and type of genetic variability help the breeder to determine the selection criteria and breeding schemes to be used for improvement purposes. A screen.
Zhang, Kunlin; Qu, Susu; Chang, Suhua; Li, Gen; Cao, Chengqi; Fang, Kechi; Olff, Miranda; Wang, Li; Wang, Jing
Posttraumatic stress disorder (PTSD) is a debilitating psychiatric syndrome with complex etiology. Studies aiming to explore genetic susceptibility and environmental triggers of PTSD have been increasing. However, the results are limited and highly heterogeneous. To understand the genetic study
Full Text Available A genetic screen to identify mutants that can increase flux in the isoprenoid pathway of yeast has been lacking. We describe a carotenoid-based visual screen built with the core carotenogenic enzymes from the red yeast Rhodosporidium toruloides. Enzymes from this yeast displayed the required, higher capacity in the carotenoid pathway. The development also included the identification of the metabolic bottlenecks, primarily phytoene dehydrogenase, that was subjected to a directed evolution strategy to yield more active mutants. To further limit phytoene pools, a less efficient version of GGPP synthase was employed. The screen was validated with a known flux increasing gene, tHMG1. New mutants in the TATA binding protein SPT15 were isolated using this screen that increased the yield of carotenoids, and an alternate isoprenoid, α-Farnesene confirming increase in overall flux. The findings indicate the presence of previously unknown links to the isoprenoid pathway that can be uncovered using this screen. Keywords: Metabolic engineering, Carotenoids, Isoprenoids, α-Farnesene, Rhodosporidium toruloides, SPT15
Cudzilo, S. [Military Univ. of Technology, Warsaw (Poland)
This paper contains some results of research on the IR-screening capability of smoke clouds generated during the combustion process of varied pyrotechnic formulations. The smoke compositions were made from some oxygen or oxygen-free mixtures containing metal and chloroorganic compounds or mixtures based on red phosphorus. The camouflage effectiveness of clouds generated by these formulations was investigated under laboratory conditions with an infrared camera. The technique employed enables determination of radiant temperature distributions in a smoke cloud treated as an energy equivalent of a grey body emission. The results of the analysis of thermographs from the camera were the basis on which the mixtures producing screens of the highest countermeasure for thermal imaging systems have been chosen. (orig.)
Dunn, Stephen J.; Khan, Imran H.; Chan, Ursula A.; Scearce, Robin L.; Melara, Claudia L.; Paul, Amber M.; Sharma, Vikram; Bih, Fong-Yih; Holzmayer, Tanya A.; Luciw, Paul A.; Abo, Arie
Human immunodeficiency virus (HIV) drugs designed to interfere with obligatory utilization of certain host cell factors by virus are less likely to encounter development of resistant strains than drugs directed against viral components. Several cellular genes required for productive infection by HIV were identified by the use of genetic suppressor element (GSE) technology as potential targets for anti-HIV drug development. Fragmented cDNA libraries from various pools of human peripheral blood mononuclear cells (PBMC) were expressed in vitro in human immunodeficiency virus type 1 (HIV-1)-susceptible cell lines and subjected to genetic screens to identify GSEs that interfered with viral replication. After three rounds of selection, more than 15 000 GSEs were sequenced, and the cognate genes were identified. The GSEs that inhibited the virus were derived from a diverse set of genes including cell surface receptors, cytokines, signaling proteins, transcription factors, as well as genes with unknown function. Approximately 2.5% of the identified genes were previously shown to play a role in the HIV-1 life cycle; this finding supports the biological relevance of the assay. GSEs were derived from the following 12 cell surface proteins: CXCR4, CCR4, CCR7, CD11C, CD44, CD47, CD68, CD69, CD74, CSF3R, GABBR1, and TNFR2. Requirement of some of these genes for viral infection was also investigated by using RNA interference (RNAi) technology; accordingly, 10 genes were implicated in early events of the viral life cycle, before viral DNA synthesis. Thus, these cell surface proteins represent novel targets for the development of therapeutics against HIV-1 infection and AIDS
Mersereau, Jennifer E; Plunkett, Beth A; Cedars, Marcelle I
To compare the strategy of traditional IVF with prenatal diagnosis versus IVF with preimplantation genetic screening (IVF/PGS) to prevent aneuploid births in women with advanced maternal age. A decision tree analytic model was created to compare IVF alone versus IVF/PGS to evaluate which strategy is the least costly per healthy (euploid) infant. Outpatient IVF practices. Infertile women, 38-40 and >40 years old. IVF or IVF/PGS. Cost per healthy infant. Using base-case estimates of costs and probabilities in women aged 38-40 years, after a maximum of two fresh IVF cycles and two frozen cycles, the chance of having a healthy infant was 37.8% with IVF alone versus 21.7% with IVF/PGS. The average cost for each strategy is $25,700, but the cost per healthy infant is substantially higher when IVF/PGS is applied as opposed to IVF alone ($118,713 vs. $68,026). To assess the robustness of the model, all probabilities were varied simultaneously in a Monte Carlo simulation, and in 96.2% of trials, IVF alone proved to be the most cost-effective option. Conversely, our data demonstrate that in women aged >40, IVF and IVF/PGS are essentially equal in terms of cost-effectiveness ($122,000 vs. $118,713). IVF alone is less costly per healthy infant than IVF/PGS in women ages 38-40.
Scott J. Neal
Full Text Available Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation.
Lynch, HT; Lynch, PM; Lanspa, SJ; Snyder, CL; Lynch, JF; Boland, CR
More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC’s proximal occurrence (70–80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10–25% of familial CRC. PMID:19659756
Dailey, Amy B; Kasl, Stanislav V; Jones, Beth A
ABSTRACT Objective: To determine if gender discrimination, conceptualized as a negative life stressor, is a deterrent to adherence to mammography screening guidelines. African American and white women (1451) aged 40-79 years who obtained an index screening mammogram at one of five urban hospitals in Connecticut between October 1996 and January 1998 were enrolled in this study. This logistic regression analysis includes the 1229 women who completed telephone interviews at baseline and follow-up (average 29.4 months later) and for whom the study outcome, nonadherence to age-specific mammography screening guidelines, was determined. Gender discrimination was measured as lifetime experience in seven possible situations. Gender discrimination, reported by nearly 38% of the study population, was significantly associated with nonadherence to mammography guidelines in women with annual family incomes of > or =$50,000 (OR 1.99, 95% CI 1.33, 2.98) and did not differ across racial/ethnic group. Our findings suggest that gender discrimination can adversely influence regular mammography screening in some women. With nearly half of women nonadherent to screening mammography guidelines in this study and with decreasing mammography rates nationwide, it is important to address the complexity of nonadherence across subgroups of women. Life stressors, such as experiences of gender discrimination, may have considerable consequences, potentially influencing health prevention prioritization in women.
Full Text Available Abstract Background Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Results Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups. Conclusion Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.
van Zonneveld, Maarten; Ramirez, Marleni; Williams, David E; Petz, Michael; Meckelmann, Sven; Avila, Teresa; Bejarano, Carlos; Ríos, Llermé; Peña, Karla; Jäger, Matthias; Libreros, Dimary; Amaya, Karen; Scheldeman, Xavier
For most crops, like Capsicum, their diversity remains under-researched for traits of interest for food, nutrition and other purposes. A small investment in screening this diversity for a wide range of traits is likely to reveal many traditional varieties with distinguished values. One objective of this study was to demonstrate, with Capsicum as model crop, the application of indicators of phenotypic and geographic diversity as effective criteria for selecting promising genebank accessions for multiple uses from crop centers of diversity. A second objective was to evaluate the expression of biochemical and agromorphological properties of the selected Capsicum accessions in different conditions. Four steps were involved: 1) Develop the necessary diversity by expanding genebank collections in Bolivia and Peru; 2) Establish representative subsets of ~100 accessions for biochemical screening of Capsicum fruits; 3) Select promising accessions for different uses after screening; and 4) Examine how these promising accessions express biochemical and agromorphological properties when grown in different environmental conditions. The Peruvian Capsicum collection now contains 712 accessions encompassing all five domesticated species (C. annuum, C. chinense, C. frutescens, C. baccatum, and C. pubescens). The collection in Bolivia now contains 487 accessions, representing all five domesticates plus four wild taxa (C. baccatum var. baccatum, C. caballeroi, C. cardenasii, and C. eximium). Following the biochemical screening, 44 Bolivian and 39 Peruvian accessions were selected as promising, representing wide variation in levels of antioxidant capacity, capsaicinoids, fat, flavonoids, polyphenols, quercetins, tocopherols, and color. In Peru, 23 promising accessions performed well in different environments, while each of the promising Bolivian accessions only performed well in a certain environment. Differences in Capsicum diversity and local contexts led to distinct outcomes in
Full Text Available BACKGROUND: Dimeric naphthoquinones (BiQ were originally synthesized as a new class of HIV integrase inhibitors but have shown integrase-independent cytotoxicity in acute lymphoblastic leukemia cell lines suggesting their use as potential anti-neoplastic agents. The mechanism of this cytotoxicity is unknown. In order to gain insight into the mode of action of binaphthoquinones we performed a systematic high-throughput screen in a yeast isogenic deletion mutant array for enhanced or suppressed growth in the presence of binaphthoquinones. METHODOLOGY/PRINCIPAL FINDINGS: Exposure of wild type yeast strains to various BiQs demonstrated inhibition of yeast growth with IC(50s in the microM range. Drug sensitivity and resistance screens were performed by exposing arrays of a haploid yeast deletion mutant library to BiQs at concentrations near their IC(50. Sensitivity screens identified yeast with deletions affecting mitochondrial function and cellular respiration as having increased sensitivity to BiQs. Corresponding to this, wild type yeast grown in the absence of a fermentable carbon source were particularly sensitive to BiQs, and treatment with BiQs was shown to disrupt the mitochondrial membrane potential and lead to the generation of reactive oxygen species (ROS. Furthermore, baseline ROS production in BiQ sensitive mutant strains was increased compared to wild type and could be further augmented by the presence of BiQ. Screens for resistance to BiQ action identified the mitochondrial external NAD(PH dehydrogenase, NDE1, as critical to BiQ toxicity and over-expression of this gene resulted in increased ROS production and increased sensitivity of wild type yeast to BiQ. CONCLUSIONS/SIGNIFICANCE: In yeast, binaphthoquinone cytotoxicity is likely mediated through NAD(PH:quonine oxidoreductases leading to ROS production and dysfunctional mitochondria. Further studies are required to validate this mechanism in mammalian cells.
Dengjel, Jörn; Høyer-Hansen, Maria; Nielsen, Maria
Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid dep...... regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection....
W.E. van den Berg (Wouter)
markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of
First page Back Continue Last page Overview Graphics. India, a paradise for Genetic Studies. The second land to be occupied by man. Human settlements & expansion 50,000 years. Sub-divided Gene pool, Nature's experiment. Sympatrically isolated gene pools. (living in the same place without mixing). may be ...
Song, Qing-Kun; Wang, Xiao-Li; Zhou, Xin-Na; Yang, Hua-Bing; Li, Yu-Chen; Wu, Jiang-Ping; Ren, Jun; Lyerly, Herbert Kim
screening program targeting women aged 35-59 years had a low detection rate that resulted in a second-generation screening program that extended the cohort size and ages screened to 35-64 years. Cancer registration has been active in China for decades; however, a national survey of registries has not been routinely reported. This study used MapInfo to describe the reported data and found asymmetric registration activities, geographic variations in breast cancer (BC) burdens, and an increasing incidence with a peak at age 50. The initial Chinese BC screening programs focused on a relatively young population of women aged 35-59 years and had a low detection rate, but 69.7% of patients had early stage BC. Older women were included in the second-generation screening programs, and an additional 6 million women were screened. Consideration of regional variations and age is necessary to optimize the efficiency and utility of BC screening in China, with the ultimate goal to reduce BC mortality. ©AlphaMed Press.
M., Adamopoulou; E.M., Pallesen; A., Levann
engineered GlycoSkin tissue models can be used to study biological interactions involving glycan structure on lipids, or glycosaminoglycans. This engineering approach will allow us to investigate the functions of glycans in homeostasis and elucidate the role of glycans in normal epithelial formation....... We use genetic engineering with CRISPR/Cas9 combined with 3D organotypic skin models to examine how distinct glycans influence epithelial formation. We have performed knockout and knockin of more than 100 select genes in the genome of human immortalized human keratinocytes, enabling a systematic...... analysis of the impact of specific glycans in the formation and transformation of the human skin. The genetic engineered human skin models (GlycoSkin) was designed with and without all major biosynthetic pathways in mammalian glycan biosynthesis, including GalNAc-O-glycans, O-fucosylation, O...
Ferrari, Raffaele; Ferrara, Michela; Alinani, Anwar; Sutton, Roger Brian; Famà, Francesco; Picco, Agnese; Rodriguez, Guido; Nobili, Flavio; Momeni, Parastoo
Cohorts from a defined geographical area enable ad hoc genotype-phenotype correlation studies providing novel and unique insight into disease. We analysed genetic risk factors associated with early and late onset Alzheimer's disease (EOAD and LOAD) in a population from Liguria (northern Italy), as part of an ongoing longitudinal study. We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT, GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU, CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1, PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer's and non-Alzheimer's forms of dementias in all dementia cases might be warranted. The analysis of the LOAD risk factors revealed no association with AD or AD + MCI status after Bonferroni correction. Lack of association with APOE is supported by previous studies in the Italian population. Our data also evidenced: 1) a potentially protective haplotype at the PSEN2 locus; 2) a nominal association with the GWAS-risk allele A for rs3818361 in CR1 and; 3) a threefold prevalence of AD in the female population compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area.
Takabatake, Reona; Onishi, Mari; Koiwa, Tomohiro; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi
A novel real-time polymerase chain reaction (PCR)-based quantitative screening method was developed for three genetically modified soybeans: RRS, A2704-12, and MON89788. The 35S promoter (P35S) of cauliflower mosaic virus is introduced into RRS and A2704-12 but not MON89788. We then designed a screening method comprised of the combination of the quantification of P35S and the event-specific quantification of MON89788. The conversion factor (Cf) required to convert the amount of a genetically modified organism (GMO) from a copy number ratio to a weight ratio was determined experimentally. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDR), respectively. The determined RSDR values for the method were less than 25% for both targets. We consider that the developed method would be suitable for the simple detection and approximate quantification of GMO.
Schoeppe, Stephanie; Rebar, Amanda L; Short, Camille E; Alley, Stephanie; Van Lippevelde, Wendy; Vandelanotte, Corneel
High screen time in children and its detrimental health effects is a major public health problem. How much screen time adults think is appropriate for children remains little explored, as well as whether adults' screen time behaviour would determine their views on screen time restrictions for children. This study aimed to investigate how adults' screen time behaviour influences their views on screen time restrictions for children, including differences by gender and parental status. In 2013, 2034 Australian adults participated in an online survey conducted by the Population Research Laboratory at Central Queensland University, Rockhampton. Adult screen time behaviour was assessed using the Workforce Sitting Questionnaire. Adults reported the maximum time children aged between 5-12 years should be allowed to spend watching TV and using a computer. Ordinal logistic regression was used to compare adult screen time behaviour with views on screen time restrictions for children. Most adults (68%) held the view that children should be allowed no more than 2 h of TV viewing and computer use on school days, whilst fewer adults (44%) thought this screen time limit is needed on weekend days. Women would impose higher screen time restrictions for children than men (p 2 h on watching TV and using the computer at home on work days (66%) and non-work days (88%). Adults spending ≤ 2 h/day in leisure-related screen time were less likely to permit children > 2 h/day of screen time. These associations did not differ by adult gender and parental status. Most adults think it is appropriate to limit children's screen time to the recommended ≤ 2 h/day but few adults themselves adhere to this screen time limit. Adults with lower screen use may be more inclined to limit children's screen time. Strategies to reduce screen time in children may also need to target adult screen use.
Full Text Available Abstract Background Screening asymptomatic individuals for neoplasia can have adverse consequences on quality of life. Colon cancer screening is widespread but the quality of life (QOL consequences are unknown. This study determined the impact of screening colonoscopy on QOL measures in asymptomatic average-risk participants. Methods Asymptomatic male and female participants aged 55–74 years were randomly selected from the Australian Electoral Roll or six primary care physicians' databases. Participants completed the Short-Form (SF-36 Quality of Life Assessment at baseline and at a mean of 39 days after colonoscopy. Outcome measures were (i significant changes in raw scores in any of the eight SF-36 domains assessed following colonoscopic screening and (ii improvements or declines in previously validated categories, representing clinically significant changes, within any of the eight SF-36 domains. Results Baseline QOL measures were similar to those of a matched general population sample. Role Limitations due to Emotions, Mental Health and Vitality raw scores significantly improved following colonoscopy (P Conclusion Average-risk persons benefit significantly from colon cancer screening with colonoscopy, improving in Mental Health and Vitality domains of Quality of Life. This improvement is not offset by declines in other domains.
Matar, A; Kihlbom, U; Höglund, A T
Reproductive autonomy, medicalization, and discrimination against disabled and parental responsibility are the main ongoing ethical debates concerning reproductive genetic screening. To examine Swedish healthcare professionals' views on preconception expanded carrier screening (ECS), a qualitative study involving academic and clinical institutions in Sweden was conducted in September 2014 to February 2015. Eleven healthcare professionals including clinicians, geneticists, a midwife, and a genetic counselor were interviewed in depth using a semi-structured interview guide. The questionnaire was constructed after reviewing the main literature and meetings with relevant healthcare providers. The interviews were recorded, transcribed verbatim, and content analyzed for categories and subcategories. Participants nurtured many ethical and non-ethical concerns regarding preconception ECS. Among the ethical concerns were the potential for discrimination, medicalization, concerns with prioritization of healthcare resources, and effects on reproductive freedom. The effects of implementation of preconception ECS, its stakeholders, regulations, and motivation are some of non-ethical concerns. These concerns, if not addressed, may affect the uptake and usage of carrier screening within Swedish healthcare system. As this is a qualitative study with a small non-random sample size, the findings cannot be generalized. The participants had little to no working experience with expanded screening panels. Moreover, the interviews were conducted in English, a second language for the participants, which might have limited the expression of their views. However, the authors claim that the findings may be pertinent to similar settings in other Scandinavian countries.
A Study on Knowledge and Screening for Cervical Cancer among Women in ... and source of information for awareness of women about cervical cancer in India. ... Results: Majority of the women have poor knowledge about cervical cancer ...
Sean F Landrette
Full Text Available Somatic forward genetic screens have the power to interrogate thousands of genes in a single animal. Retroviral and transposon mutagenesis systems in mice have been designed and deployed in somatic tissues for surveying hematopoietic and solid tumor formation. In the context of cancer, the ability to visually mark mutant cells would present tremendous advantages for identifying tumor formation, monitoring tumor growth over time, and tracking tumor infiltrations and metastases into wild-type tissues. Furthermore, locating mutant clones is a prerequisite for screening and analyzing most other somatic phenotypes. For this purpose, we developed a system using the piggyBac (PB transposon for somatic mutagenesis with an activated reporter and tracker, called PB-SMART. The PB-SMART mouse genetic screening system can simultaneously induce somatic mutations and mark mutated cells using bioluminescence or fluorescence. The marking of mutant cells enable analyses that are not possible with current somatic mutagenesis systems, such as tracking cell proliferation and tumor growth, detecting tumor cell infiltrations, and reporting tissue mutagenesis levels by a simple ex vivo visual readout. We demonstrate that PB-SMART is highly mutagenic, capable of tumor induction with low copy transposons, which facilitates the mapping and identification of causative insertions. We further integrated a conditional transposase with the PB-SMART system, permitting tissue-specific mutagenesis with a single cross to any available Cre line. Targeting the germline, the system could also be used to conduct F1 screens. With these features, PB-SMART provides an integrated platform for individual investigators to harness the power of somatic mutagenesis and phenotypic screens to decipher the genetic basis of mammalian biology and disease.
Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie
Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.
Gallistel, C R; Balci, Fuat; Freestone, David; Kheifets, Aaron; King, Adam
We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the "cloud" and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in cabinet; two such cabinets (16 environments) may be
Gina M. Zastrow-Hayes
Full Text Available Molecular characterization of events is an integral part of the advancement process during genetically modified (GM crop product development. Assessment of these events is traditionally accomplished by polymerase chain reaction (PCR and Southern blot analyses. Southern blot analysis can be time-consuming and comparatively expensive and does not provide sequence-level detail. We have developed a sequence-based application, Southern-by-Sequencing (SbS, utilizing sequence capture coupled with next-generation sequencing (NGS technology to replace Southern blot analysis for event selection in a high-throughput molecular characterization environment. SbS is accomplished by hybridizing indexed and pooled whole-genome DNA libraries from GM plants to biotinylated probes designed to target the sequence of transformation plasmids used to generate events within the pool. This sequence capture process enriches the sequence data obtained for targeted regions of interest (transformation plasmid DNA. Taking advantage of the DNA adjacent to the targeted bases (referred to as next-to-target sequence that accompanies the targeted transformation plasmid sequence, the data analysis detects plasmid-to-genome and plasmid-to-plasmid junctions introduced during insertion into the plant genome. Analysis of these junction sequences provides sequence-level information as to the following: the number of insertion loci including detection of unlinked, independently segregating, small DNA fragments; copy number; rearrangements, truncations, or deletions of the intended insertion DNA; and the presence of transformation plasmid backbone sequences. This molecular evidence from SbS analysis is used to characterize and select GM plants meeting optimal molecular characterization criteria. SbS technology has proven to be a robust event screening tool for use in a high-throughput molecular characterization environment.
Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.
Rudo L Simeon
Full Text Available Genetic suppressor elements (GSEs are biomolecules derived from a gene or genome of interest that act as transdominant inhibitors of biological functions presumably by disruption of critical biological interfaces. We exploited a cell death reporter cell line for hepatitis C virus (HCV infection, n4mBid, to develop an iterative selection/enrichment strategy for the identification of anti-HCV GSEs. Using this approach, a library of fragments of an HCV genome was screened for sequences that suppress HCV infection. A 244 amino acid gene fragment, B1, was strongly enriched after 5 rounds of selection. B1 derives from a single-base frameshift of the enhanced green fluorescent protein (eGFP which was used as a filler during fragment cloning. B1 has a very high net positive charge of 43 at neutral pH and a high charge-to-mass (kDa ratio of 1.5. We show that B1 expression specifically inhibits HCV replication. In addition, five highly positively charged B1 fragments produced from progressive truncation at the C-terminus all retain the ability to inhibit HCV, suggesting that a high positive charge, rather than a particular motif in B1, likely accounts for B1's anti-HCV activity. Another supercharged protein, +36GFP, was also found to strongly inhibit HCV replication when added to cells at the time of infection. This study reports a new methodology for HCV inhibitor screening and points to the anti-HCV potential of positively charged proteins/peptides.
Fendler, W; Borowiec, M; Baranowska-Jazwiecka, A; Szadkowska, A; Skala-Zamorowska, E; Deja, G; Jarosz-Chobot, P; Techmanska, I; Bautembach-Minkowska, J; Mysliwiec, M; Zmyslowska, A; Pietrzak, I; Malecki, M T; Mlynarski, W
The aim of this study was to study dynamic changes in the prevalence of different types of diabetes in paediatric populations in Poland, with a specific focus on monogenic diabetes (MD). Using epidemiologic data (PolPeDiab Collaboration) and nationwide genetic test results (TEAM Programme), we compared the prevalence of type 1, type 2 and cystic fibrosis-related diabetes (CFRD) and MD. Genetically confirmed MD included MODY, neonatal diabetes and Wolfram and Alström syndromes. The study covered all children aged 0-18 years treated for diabetes between 2005 and 2011 in three regions, inhabited by 23.7% (1,989,988) of Polish children, with a low prevalence of childhood obesity (type 1 diabetes showed a continuous increase, from 96 to 138/100,000 children. The prevalence of type 2 diabetes and CFRD also increased, from 0.3 to 1.01/100,000 children and from 0.1 to 0.95/100,000 children, respectively. The prevalence of MD was stable at between 4.2 and 4.6/100,000 children, accounting for 3.1-4.2% of children with diabetes, with glucokinase (GCK)-MODY being the most frequent type, amounting to 83% of patients with MD. The percentage of positive test results decreased with the number of referrals, suggesting that children with the highest probability of MD were referred initially, followed by those with a less clear-cut phenotype. The prevalence of neonatal diabetes equalled 1 in 300,000 children. The prevalence of MD in a paediatric population with a low prevalence of obesity remains stable and is nearly fivefold higher than that of type 2 diabetes and CFRD, justifying a need for increased access to genetic diagnostic procedures in diabetic children.
Cecelia A. Bellcross
Full Text Available Newborn screening (NBS follow-up protocols vary significantly by state, and there is a need to better understand the infrastructure and communication flow of NBS programs. In addition, assessment of the educational needs of families and providers with regard to the implications of NBS results is required to inform the development of appropriate informational resources and training opportunities. To begin to address these issues, we administered a web-based survey to state NBS coordinators within the Southeast Regional Newborn Screening & Genetics Collaborative (SERC. Fourteen coordinators responded to the survey, including at least one from each of the 10 SERC states/territories. Over one-third of respondents had never received formal training regarding the metabolic conditions identified on NBS. Most communicated results via telephone or fax, though two centers indicated use of a web-based platform. Only two programs were involved in directly reporting results to the family. Four programs reported a long-term follow-up protocol. Deficits were noted for primary care provider (PCP knowledge of metabolic disorders identified on NBS, and how to inform parents of abnormal results. Close to half indicated that the adequacy of the number of genetic counselors, dietitians, and medical/biochemical geneticists was minimal to insufficient. Respondents uniformly recognized the importance of providing additional educational and informational resources in multiple categories to NBS staff, PCPs, and families.
Heijink, Anne Margriet; Blomen, Vincent A; Bisteau, Xavier; Degener, Fabian; Matsushita, Felipe Yu; Kaldis, Philipp; Foijer, Floris; van Vugt, Marcel A T M
The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the existence of genetic determinants of Wee1 inhibitor sensitivity other than TP53 status. To optimally facilitate patient selection for Wee1 inhibition and uncover potential resistance mechanisms, identification of these currently unknown genes is necessary. The aim of this study was therefore to identify gene mutations that determine Wee1 inhibitor sensitivity. We performed a genome-wide unbiased functional genetic screen in TP53 mutant near-haploid KBM-7 cells using gene-trap insertional mutagenesis. Insertion site mapping of cells that survived long-term Wee1 inhibition revealed enrichment of G1/S regulatory genes, including SKP2, CUL1, and CDK2. Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the γ-H2AX induction and abrogation of G2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. Remarkably, live cell imaging showed that depletion of SKP2, CUL1, or CDK2 did not rescue the Wee1 inhibition-induced karyokinesis and cytokinesis defects. These data indicate that the activity of the DNA replication machinery, beyond TP53 mutation status, determines Wee1 inhibitor sensitivity, and could serve as a selection criterion for Wee1-inhibitor eligible patients. Conversely, loss of the identified S-phase genes could serve as a mechanism of acquired resistance, which goes along with development of severe genomic instability.
Colaianni, Alessandra; Chandrasekharan, Subhashini; Cook-Deegan, Robert
Genetic testing for Tay-Sachs and Canavan disease is particularly important for Ashkenazi Jews, because both conditions are more frequent in that population. This comparative case study was possible because of different patenting and licensing practices. The role of DNA testing differs between Tay-Sachs and Canavan diseases. The first-line screening test for Tay-Sachs remains an enzyme activity test rather than genotyping. Genotyping is used for preimplantation diagnosis and confirmatory testing. In contrast, DNA-based testing is the basis for Canavan screening and diagnosis. The HEXA gene for Tay-Sachs was cloned at the National Institutes of Health, and the gene was patented but has not been licensed. The ASPA gene for Canavan disease was cloned and patented by Miami Children's Hospital. Miami Children's Hospital did not inform family members and patient groups that had contributed to the gene discovery that it was applying for a patent, and pursued restrictive licensing practices when a patent issued in 1997. This led to intense controversy, litigation, and a sealed, nonpublic 2003 settlement that apparently allowed for nonexclusive licensing. A survey of laboratories revealed a possible price premium for ASPA testing, with per-unit costs higher than for other genetic tests in the Secretary's Advisory Committee on Genetics, Health, and Society case studies. The main conclusion from comparing genetic testing for Tay-Sachs and Canavan diseases, however, is that patenting and licensing conducted without communication with patients and advocates cause mistrust and can lead to controversy and litigation, a negative model to contrast with the positive model of patenting and licensing for genetic testing of cystic fibrosis.
Full Text Available Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen of a transposon mutant library to study the molecular mechanisms involved in persistence of community-acquired S. aureus. Screening of the library for mutants defective in persistence or tolerance to rifampicin revealed many genes involved in metabolic pathways that are important for antibiotic persistence. In particular, the identified mutants belonged to metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and purine biosynthesis. Five mutants played a role in purine biosynthesis and two mutants, purB, an adenylosuccinate lyase, and purM, a phosphoribosylaminoimidazole synthetase, were selected for further confirmation. Mutants purB and purM showed defective persistence compared to the parental strain USA300 in multiple stress conditions including various antibiotics, low pH, and heat stress. The defect in persistence was restored by complementation with the wildtype purB and purM gene in the respective mutants. These findings provide new insights into the mechanisms of persistence in S. aureus and provide novel therapeutic targets for developing more effective treatment for persistent infections due to S. aureus.
Rogowski, Wolf H
Genetic tests for hereditary hemochromatosis (HH) are currently included in the German ambulatory care reimbursement scheme but only for symptomatic individuals and the offspring of HH patients. This study synthesizes the most current evidence to examine whether screening in the broader population is cost-effective and to identify the best choice of initial and follow-up screening tests. A probabilistic decision-analytic model was constructed to calculate cost per life year gained (LYG) for HH screening among male Caucasians aged 30. Three strategies were considered in both the general population and male offspring of HH patients: phenotypic (transferrin saturation, TS), genotypic (C282Y mutation), and sequential (genotype if TS is elevated) screening. The incremental cost-effectiveness of sequential screening among male offspring, sequential population-wide screening, and genotypic screening is 41000, 124000, and 161000 Eero/LYG, respectively. All other strategies were subject to simple or extended dominance. The results are subject to high uncertainty. The most influential parameters in the deterministic one-way sensitivity analysis are discounting of life years gained and the adherence of patients to preventive phlebotomy. The current German policy of only screening at-risk individuals is consistent with health economic decision making based on typically accepted thresholds. However, conducting the DNA test after the first elevated TS result is more cost-effective than waiting for a second TS result as recommended by the German guidelines. Further empirical work regarding adherence to long-term prevention recommendations and explicit and well-justified guidance for the choice of discount rates in German economic evaluation are needed.
Full Text Available Bacterial infection of plants often begins with colonization of the plant surface, followed by entry into the plant through wounds and natural openings (such as stomata, multiplication in the intercellular space (apoplast of the infected tissues, and dissemination of bacteria to other plants. Historically, most studies assess bacterial infection based on final outcomes of disease and/or pathogen growth using whole infected tissues; few studies have genetically distinguished the contribution of different host cell types in response to an infection. The phytotoxin coronatine (COR is produced by several pathovars of Pseudomonas syringae. COR-deficient mutants of P. s. tomato (Pst DC3000 are severely compromised in virulence, especially when inoculated onto the plant surface. We report here a genetic screen to identify Arabidopsis mutants that could rescue the virulence of COR-deficient mutant bacteria. Among the susceptible to coronatine-deficient Pst DC3000 (scord mutants were two that were defective in stomatal closure response, two that were defective in apoplast defense, and four that were defective in both stomatal and apoplast defense. Isolation of these three classes of mutants suggests that stomatal and apoplastic defenses are integrated in plants, but are genetically separable, and that COR is important for Pst DC3000 to overcome both stomatal guard cell- and apoplastic mesophyll cell-based defenses. Of the six mutants defective in bacterium-triggered stomatal closure, three are defective in salicylic acid (SA-induced stomatal closure, but exhibit normal stomatal closure in response to abscisic acid (ABA, and scord7 is compromised in both SA- and ABA-induced stomatal closure. We have cloned SCORD3, which is required for salicylic acid (SA biosynthesis, and SCORD5, which encodes an ATP-binding cassette (ABC protein, AtGCN20/AtABCF3, predicted to be involved in stress-associated protein translation control. Identification of SCORD5 begins to
Beukers, F.; Houtzager, B. A.; Paap, M C S; Middelburg, K J; Hadders-Algra, M; Bos, A.F.; Kok, J.H.
Background: Infertility treatment has an acknowledged psychological impact on women and their partners; however, information about the development of parental well-being after child birth is inconclusive. Preimplantation genetic screening (PGS) has been suggested to increase the efficacy of
Beukers, F.; Houtzager, B. A.; Paap, M. C. S.; Middelburg, K. J.; Hadders-Algra, M.; Bos, A. F.; Kok, J. H.; Cobben, Jan Maarten; van der Heide, Maaike; Koomen, Alice; Repping, Sjoerd; Silberbusch, Lobke; Twisk, Moniek; Mastenbroek, Sebastiaan; van der Veen, Fulco; Bos, Arend F.; Haadsma, Maaike; Hadders-Algra, Mijna; Heineman, Maas Jan; van Hoften, Jacorina; Jongbloed-Pereboom, Marjolein; Keating, Paul; Seggers, Jorien
Background: Infertility treatment has an acknowledged psychological impact on women and their partners; however, information about the development of parental well-being after child birth is inconclusive. Preimplantation genetic screening (PGS) has been suggested to increase the efficacy of
Beukers, F.; Houtzager, B.A.; Paap, Muirne; Middelburg, K.; Hadders-Algra, M.; Bos, A.F.; Kok, J.H.
Background Infertility treatment has an acknowledged psychological impact on women and their partners; however, information about the development of parental well-being after child birth is inconclusive. Preimplantation genetic screening (PGS) has been suggested to increase the efficacy of
Full Text Available A common limitation for the identification of novel activities from functional (meta genomic screens is the low number of active clones detected relative to the number of clones screened. Here we demonstrate that constructing libraries with strains known to produce bioactives can greatly enhance the screening efficiency, by increasing the “hit-rate” and unmasking multiple activities from the same bacterial source.
Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. (Morehouse Coll., Atlanta, GA (United States). School of Medicine); Crandall, L.A.; Moseley, R.E.; Armotrading, D. (Florida Univ., Gainesville, FL (United States). Coll. of Medicine)
Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia's system of Children's Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.
Tradescantia in studies on genetic effects of low level radiation is briefly introduced. Radiosensitivity, method of screening stamen hair mutation, materials in current uses, spontaneous mutation rate, and modifying factors are refered. For stamen hair mutation b values in exponential model were lower in irradiation with low dose rate at high environmental temperature. The dose response curves under these modifying conditions, when extrapolated to low dose range, well fit to the line which was obtained by Sparrow's experiment of low level irradiation. In chronic irradiation, the frequency of stamen hair mutation reaches to the constant value after 17 days from the start of irradiation, and is as much as 4 times higher than the peak value in one day irradiation at the same exposure rate. The spontaneous mutation rate of KU-7 varied with temperature. The increase with 1 0 C increment of mean temperature was -0.04%. Uses of Tradescantia in monitoring the environmental radiation is discussed. (auth.)
Weichbold, Viktor; Rohrer, Monika; Winkler, Cornelia; Welzl-Müller, Kunigunde
This study aimed to evaluate the hearing screening of pre-school children at nursery schools in Tyrol, Austria. 47 nursery schools with a total of 2199 enrolled children participated in the study. At the screening, the children were presented a series of tones at frequencies 0.5 kHz (25dB), 1 kHz, 2 kHz, 3 kHz, and 4 kHz (20 dB each) from portable audiometers. The tones were presented over headphones for each ear separately and at irregular intervals. Failure to respond to any of the frequencies was considered failure of the screening. Parents were then advised in written form to have the child examined by an ENT-specialist. 1832 individuals were screened (coverage: 83% of nursery school children; corresponding to at least 63% of all Tyrolean children aged 3 to 5 years). Of these, 390 failed the test (referral rate: 21% of all screened). Examination through an ENT-specialist occurred with 217 children, and this confirmed the positive test in 139 children (hit rate: 64%). In most cases, a temporary conductive hearing loss due to external or middle ear problems (glue ear, tube dysfunction, cerumen, otitis media) was diagnosed. A sensorineural hearing loss was found in 4 children (in 3 of them bilateral). The need for therapy was recognized in 81 children (4% of all screened). Pre-school hearing screening identifies children with ear and hearing problems that need therapeutical intervention. Although the hearing problems are mostly of a temporary nature, some may require monitoring over some period. Also some children with permanent sensorineural hearing loss may be detected through this measure. Hearing screening is an efficient means of assessing ear and hearing problems in pre-school children. However, the follow-up rate needs to be improved for optimizing the efficacy.
Noguchi, Akio; Nakamura, Kosuke; Sakata, Kozue; Sato-Fukuda, Nozomi; Ishigaki, Takumi; Mano, Junichi; Takabatake, Reona; Kitta, Kazumi; Teshima, Reiko; Kondo, Kazunari; Nishimaki-Mogami, Tomoko
A number of genetically modified (GM) maize events have been developed and approved worldwide for commercial cultivation. A screening method is needed to monitor GM maize approved for commercialization in countries that mandate the labeling of foods containing a specified threshold level of GM crops. In Japan, a screening method has been implemented to monitor approved GM maize since 2001. However, the screening method currently used in Japan is time-consuming and requires generation of a calibration curve and experimental conversion factor (C(f)) value. We developed a simple screening method that avoids the need for a calibration curve and C(f) value. In this method, ΔC(q) values between the target sequences and the endogenous gene are calculated using multiplex real-time PCR, and the ΔΔC(q) value between the analytical and control samples is used as the criterion for determining analytical samples in which the GM organism content is below the threshold level for labeling of GM crops. An interlaboratory study indicated that the method is applicable independently with at least two models of PCR instruments used in this study.
This study by Lockwood Greene evaluates a number ironmaking processes. The appendices provide greater detail and further exploration of the ironmaking processes, including components, relative costs, and comparisons.
Samelli, Alessandra Giannella; Negretti, Camila Aparecida; Ueda, Kerli Saori; Moreira, Renata Rodrigues; Schochat, Eliane
Given the high prevalence of presbycusis and the damage it brings about, a screening test can be useful in the identification of hearing loss in primary care. To estimate the prevalence of hearing loss in a representative sample of elderly people living at Butantan using an audiological screening method (questionnaire) and a basic audiological evaluation; to compare the results of the two kinds of evaluations, checking the validity of this tool for hearing loss screening. Cross sectional descriptive study. 200 individuals (above 60 years old, both genders) were randomly selected to undergo audiological screening (questionnaire). Another randomly selected group encompassed 100 individuals who were submitted to a set of audiological tests. Then, we compared the results from the two methods. There were no statistically significant associations between the questionnaire and the degree of hearing loss of the patients. The prevalence of hearing loss in our sample was of 56% in the screening and of 95% when checked by the audiological evaluation. Therefore, screening was not proven valid to assess hearing when compared to audiological evaluation.
Dóra J. Eszes
Full Text Available Introduction. Diabetic retinopathy (DR is a sight-threatening complication of diabetes. Telemedicine tools can prevent blindness. We aimed to investigate the patients’ satisfaction when using such tools (fundus camera examination and the effect of demographic and socioeconomic factors on participation in screening. Methods. Pilot study involving fundus camera screening and self-administered questionnaire on participants’ experience during fundus examination (comfort, reliability, and future interest in participation, as well as demographic and socioeconomic factors was performed on 89 patients with known diabetes in Csongrád County, a southeastern region of Hungary. Results. Thirty percent of the patients had never participated in any ophthalmological screening, while 25.7% had DR of some grade based upon a standard fundus camera examination and UK-based DR grading protocol (Spectra™ software. Large majority of the patients were satisfied with the screening and found it reliable and acceptable to undertake examination under pupil dilation; 67.3% were willing to undergo nonmydriatic fundus camera examination again. There was a statistically significant relationship between economic activity, education and marital status, and future interest in participation. Discussion. Participants found digital retinal screening to be reliable and satisfactory. Telemedicine can be a strong tool, supporting eye care professionals and allowing for faster and more comfortable DR screening.
Cornel, M.C.; van El, C.G.; Dondorp, W.J.
New screening possibilities become available at a high rate, both useful and unsound possibilities. All screening programmes do harm, and only few have more advantages than disadvantages at reasonable cost. Horizon scanning is needed to identify those few possibilities with more pros than cons.
Jun 30, 2013 ... Objectives: In this study, methanol, ethanol and aqueous extracts of ... of resistance in bacteria previously susceptible to ... increase in antibiotic resistance in hospitals and ..... extraction process (Masoko et al., 2008). Use of ...
Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.
Fu, Wei; Wei, Shuang; Wang, Chenguang; Du, Zhixin; Zhu, Pengyu; Wu, Xiyang; Wu, Gang; Zhu, Shuifang
High throughput screening systems are the preferred solution to meet the urgent requirement of increasing number of genetically modified organisms (GMOs). In this study, we have successfully developed a multiplex GMO element screening system with dual priming oligonucleotide (DPO) primers. This system can detect the cauliflower mosaic virus 35S (CaMV 35S), terminator of nopaline synthase gene (NOS), figwort mosaic virus 35S (FMV 35S) promoter, neomycin phosphotransferaseII (NPTII), Bt Cry 1Ab, phosphinothricin acetyltransferase genes (bar) and Streptomyces viridochromogenes (pat) simultaneously, which covers more than 90% of all authorized GMO species worldwide. This system exhibits a high tolerance to annealing temperatures, high specificity and a limit of detection equal to conventional PCR. A total of 214 samples from markets, national entry-exit agencies, the Institute for Reference Materials and Measurement (IRMM) and the American Oil Chemists' Society (AOCS) were also tested for applicability. This screening system is therefore suitable for GMO screening. Copyright © 2017 Elsevier Ltd. All rights reserved.
Hu, Guo-Xin; Dai, Da-Peng; Wang, Hao; Huang, Xiang-Xin; Zhou, Xiao-Yang; Cai, Jie; Chen, Hao; Cai, Jian-Ping
To systematically investigate the genetic polymorphisms of the CYP3A4 gene in a Han Chinese population. The promoter and exons of CYP3A4 gene in 1114 unrelated, healthy Han Chinese subjects were amplified and genotyped by direct sequencing. In total, five previously reported alleles (*1G, *4, *5, *18B and *23) were detected, of which one allele (*23) was reported for the first time in Han Chinese population. Additionally, seven novel exonic variants were also identified and designated as new alleles CYP3A4*28-*34. This study provides the most comprehensive data of CYP3A4 polymorphisms in Han Chinese population and detects the largest number of novel CYP3A4 alleles in one ethnic group.
Grzegorzewski, B.; Peresunko, O. P.; Yermolenko, S. B.
This work is devoted to the substantiation and selection of patients with ovarian cancer (OC) for the purpose of conducting expensive molecular genetic studies on genotyping. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5 - 25 microns) dry residue of plasma polarization and laser diagnostic technique of thin histological sections of biological tissues. Obtained results showed that the use of spectrophotometry in the range of 1000-3000 cm-1 allowed to establish quantitative parameters of the plasma absorption rate of blood of patients in the third group in different ranges, which would allow in the future to conduct an express analysis of the patient's condition (procedure screening) for further molecular-genetic typing on BRCA I and II.
Luhrsen, K.R.; Hudepohl, G.R.; Smith, K.T.
Calcium bioavailability has been studied by numerous techniques. The authors report here the use of the gamma emitting isotope of calcium ( 47 Ca) in a whole body retention assay system. In this system, calcium sources are administered by oral gavage and subsequent counts are determined and corrected for isotopic decay. Unlike iron and zinc retention curves, which exhibit a 2-3 day equilibration period, calcium reaches equilibration after 24 hours. Autoradiographic analysis of the femurs indicate that the newly absorbed calcium is rapidly distributed to the skeletal system. Moreover, the isotope is distributed along the entire bone. Comparisons of calcium bioavailability were made using intrinsic/extrinsic labeled milk from two species i.e. rat and goat as well as CaCO 3 . In addition, extrinsic labeled cow milk was examined. In the rat, the extrinsic labeled calcium from milk was better absorbed than the intrinsic calcium. This was not the case in goat milk or the calcium carbonate which exhibited no significant differences. Chromatographic analysis of the labeled milk indicates a difference in distribution of the 47 Ca. From these data, the authors recommend the use of this assay system in calcium bioavailability studies. The labeling studies and comparisons indicate caution should be used, however, in labeling techniques and species milk comparison
N. Amin (Najaf)
textabstractHuman behavioural genetics aims to unravel the genetic and environmental contributions to variations in human behaviour. Behaviour is a complex trait, involving multiple genes that are affected by a variety of other factors. Genetic epidemiological research of behaviour goes back to
Fagela-Domingo, C; Padilla, C D; Cutiongco, E M
From June 1996 to June 1998 a total of 62.841 newborn infants were screened for congenital hypothyroidism with thyroid stimulating hormone assay as a primary test. The method used was an immunofluorescent assay using the DELFIA TSH Kit on dried blood specimens collected by heelprick on filter paper. All infants with TSH values greater than 20 microU/ml were retested. If the results remained abnormally high, confirmatory testing was done by radioimmunoassay. All infants who were confirmed to be hypothyroid were referred to pediatric endocrinologists for initial management. The overall weighted incidence of congenital hypothyroidism obtained in this study was 0.000277 (95% CI; 0.000122 - 0.000432) or 1:3,610 which may be higher than that reported by most screening programs worldwide. The recall rate was 0.16%. The higher recall rate may be explained by early testing in a number of cases and by the possibility of iodine deficiency in some of the mothers. On the basis of the results of this study, we would recommend (1) screening on a greater number of infants to verify the incidence of CH and (2) establishing normal TSH values at different hours of life to improve our recall rate.
A combined analysis of 48 type 2 diabetes genetic risk variants shows no discriminative value to predict time to first prescription of a glucose lowering drug in Danish patients with screen detected type 2 diabetes
Hornbak, Malene; Allin, Kristine Højgaard; Jensen, Majken Linnemann
OBJECTIVE: To investigate the genetic influence of 48 type 2 diabetes susceptibility variants on disease progression measured as risk of early prescription redemption of glucose lowering drugs in screen-detected patients with type 2 diabetes. METHODS: We studied type 2 diabetes progression in 1...... according to either a conventional or a multifactorial intensive treatment algorithm. We investigated the genetic influence on diabetes progression by constructing a genetic risk score (GRS) of all 48 validated type 2 diabetes susceptibility variants, a GRS of 11 variants linked to β-cell function and a GRS...
Takyi, Afua; Santolaya-Forgas, Joaquin
Obstetricians offer prenatal screening for most common chromosomal abnormalities to all pregnant women including those that had in vitro fertilization (IVF) and preimplantation genetic screening/diagnosis (PGS/D). We propose that free fetal DNA in maternal circulation together with the second trimester maternal serum alfa feto protein (MSAFP) and ultrasound imaging is the best prenatal screening test for chromosomal abnormalities and congenital anomalies in IVF-PGD/S patients because risk estimations from all other prenatal screening algorithms for chromosomal abnormalities depend heavily on maternal age which is irrelevant in PGS/D patients.
Zhang, J; Wang, Y N; Wang, J S; Wu, L; Wei, N; Fu, L; Gao, Z; Chen, J H; Pei, R J; Wang, Z
To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH). Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations. The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a). Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.
Garbett, Nichola C.; Chaires, Jonathan B.
Introduction A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. Areas covered This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 – 2011 using the Science Citation Index and PUBMED and the keywords listed below. Expert opinion The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically-driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development towards an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. PMID:22458502
Garbett, Nichola C; Chaires, Jonathan B
A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 - 2011 using the Science Citation Index and PUBMED and the keywords listed below. The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development toward an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in the design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. © 2012 Informa UK, Ltd.
[Gupta A. K., Chauhan M., Tandon S. N. and Sonia 2005 Genetic diversity and bottleneck studies in the Marwari horse breed. J. Genet. 84, 295–301] ... developed to carry out studies of genetic variation (Brad- ley et al. 1996; Canon et al. ..... 1996 Mitochondrial diversity and the origins of African and. European cattle. Proc.
Full Text Available Background: Dilated Cardiomyopathy (DCM is a genetic disorder where a heterogeneous group of cardiac-muscles are involved and is characterized by ventricular dilatation, impaired systolic function, reduced myocardial contractility with left ventricular ejection fraction (LVEF less than 40%. Our study aims to report the Demographic, Clinical and Genetic profile of Indian Dilated Cardiomyopathy patients. Methodology: All patients were recruited with prior written informed consent and are of Indian origin. Results: In a total of 80 DCM patients, the prevalence was higher among males. In males, mean age of onset was comparatively less than females. In this cohort, 40% had familial inheritance. Sixty two percent of DCM patients belong to NYHA functional class II with ejection fraction (EF ranging between 21-30% and, around one third of the patients had atrial fibrillation (AF. Genetic screening revealed a novel splice site mutation LMNA (c.639+ G>C and a rare variant MYH7 (c.2769 C>T in a patient and insilico analysis of both variants suggested functional changes that were considered pathogenic. We report 3% and 4% occurance of variants, each in LMNA and MYH7, where as reported frequencies of these genes are 6% LMNA and 4% MYH7. Conclusions: DCM is often familial and all possible candidate genes should be screened to identify mutations. Such type of exercise may help in the identification of mechanistic pathways. Next generation sequencing platforms may play an important role in this respect in future.
Frankum, J.; Moudrý, P.; Brough, R.; Hodný, Zdeněk; Ashworth, A.; Bartek, Jiří; Lord, C.J.
Roč. 6, č. 13 (2015), s. 10746-10758 ISSN 1949-2553 R&D Projects: GA ČR GA13-17555S EU Projects: European Commission HEALTH-F2-2010-259893 Grant - others:Lundbeck Foundation(DK) R93-A8990; Danish Council for Independent Research(DK) DFF-1331-00262 Institutional support: RVO:68378050 Keywords : DNA damage response * ubiquitin-proteasome system * RNA interference screens * PARP inhibitors * CBLC Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.008, year: 2015
Lockwood Greene, . .
Iron in the United States is largely produced from iron ore mined in the United States or imported from Canada or South America. The iron ore is typically smelted in Blast Furnaces that use primarily iron ore, iron concentrate pellets metallurgical coke, limestone and lime as the raw materials. Under current operating scenarios, the iron produced from these Blast Furnaces is relatively inexpensive as compared to current alternative iron sources, e.g. direct iron reduction, imported pig iron, etc. The primary problem the Blast Furnace Ironmaking approach is that many of these Blast furnaces are relatively small, as compared to the newer, larger Blast Furnaces; thus are relatively costly and inefficient to operate. An additional problem is also that supplies of high-grade metallurgical grade coke are becoming increasingly in short supply and costs are also increasing. In part this is due to the short supply and costs of high-grade metallurgical coals, but also this is due to the increasing necessity for environmental controls for coke production. After year 2003 new regulations for coke product environmental requirement will likely be promulgated. It is likely that this also will either increase the cost of high-quality coke production or will reduce the available domestic U.S. supply. Therefore, iron production in the United States utilizing the current, predominant Blast Furnace process will be more costly and would likely be curtailed due to a coke shortage. Therefore, there is a significant need to develop or extend the economic viability of Alternate Ironmaking Processes to at least partially replace current and declining blast furnace iron sources and to provide incentives for new capacity expansion. The primary conclusions of this comparative Study of Alternative Ironmaking Process scenarios are: (1) The processes with the best combined economics (CAPEX and OPEX impacts in the I.R.R. calculation) can be grouped into those Fine Ore based processes with no scrap
Zhou, Qin-Wei; Zhang, Shuo-Ping; Lu, Chang-Fu; Gong, Fei; Tan, Yue-Qiu; Lu, Guang-Xiu; Lin, Ge
Background The use of assisted reproductive technology (ART) has been reported to increase the incidence of monozygotic twinning (MZT) compared with the incidence following natural conception. It has been hypothesized that splitting of the inner cell mass (ICM) through a small zona hole may result in MZT. In this study, using a cohort of patients undergoing preimplantation genetic diagnosis/screening (PGD/PGS), we compared the clinical and neonatal outcomes of human 8-shaped blastocysts hatching with ICM incarceration with partially or fully hatched blastocysts, and attempted to verify whether this phenomenon increases the incidence of MZT pregnancy or negatively impact newborns. Methods This retrospective study included 2059 patients undergoing PGD/PGS between March 1, 2013, and December 31, 2015. Clinical and neonatal outcomes were only collected from patients who received a single blastocyst transfer after PGD/PGS (n = 992). A 25- to 30-μm hole was made in the zona of day 3 embryos by laser. The blastocysts were biopsied and vitrified on day 6. The biopsied trophectoderm (TE) cells were analyzed using different genetic methods. One tested blastocyst was thawed and transferred to each patient in the subsequent frozen embryo transfer cycle. All the biopsied blastocysts were divided into three types: 8-shaped with ICM incarceration (type I), partially hatched without ICM incarceration (type II), and fully hatched (type III). ICM/TE grading, clinical and neonatal outcomes were compared between the groups. Results The percentage of grade A ICMs in type I blastocysts (22.2%) was comparable to that in type III blastocysts (20.1%) but higher than that in type II blastocysts (4.5%). The percentage of grade A TEs in type I blastocysts (4.2%) was comparable to that in type II (3.6%) but lower than that in type III (13.5%). There were no significant differences in clinical pregnancy, MZT pregnancy, miscarriage, live birth, MZT births, and neonatal outcomes between the
Kitada, Masahiro; Sakai, Hiroko; Kubo, Yoshihiko; Samejima, Natsuki; Kurowarabi, Kunio; Iwabuchi, Shuji.
In order to examine the rate of correct diagnosis by mammography at initial mass screening for breast cancer, we carried out a retrospective study of mammography findings in 267 cases of breast cancer detected at Asahikawa Cancer Screening Center. The screening was performed by physical examination, and in cases where disease was suspected, mammography, ultrasonography, and needle biopsy were done. Mammographically, 172 cases (64.4%) were cancer-positive, 58 cases (21.7%) were suspicious for cancer, and 37 cases (13.9%) were cancer-negative. Patients below 50 years of age and those with tumors of small diameter (<20 mm) showed a significantly lower rate of cancer positivity than patients aged 50 years or more and those with tumors 20 mm or more in diameter. Mammographic abnormalities were not specific, since these changes were also found in normal subjects and patients with benign diseases. Therefore, we concluded that mammography without physical examination at initial mass screening has a high risk of missing breast cancer. Mass screening for breast cancer should be performed by physical examination involving inspection and palpation at the first instance. If any suspicious findings are obtained, mammography, ultrasonography, and needle biopsy should be done. (author)
Full Text Available Abstract Background High screen time in children and its detrimental health effects is a major public health problem. How much screen time adults think is appropriate for children remains little explored, as well as whether adults’ screen time behaviour would determine their views on screen time restrictions for children. This study aimed to investigate how adults’ screen time behaviour influences their views on screen time restrictions for children, including differences by gender and parental status. Methods In 2013, 2034 Australian adults participated in an online survey conducted by the Population Research Laboratory at Central Queensland University, Rockhampton. Adult screen time behaviour was assessed using the Workforce Sitting Questionnaire. Adults reported the maximum time children aged between 5–12 years should be allowed to spend watching TV and using a computer. Ordinal logistic regression was used to compare adult screen time behaviour with views on screen time restrictions for children. Results Most adults (68 % held the view that children should be allowed no more than 2 h of TV viewing and computer use on school days, whilst fewer adults (44 % thought this screen time limit is needed on weekend days. Women would impose higher screen time restrictions for children than men (p 2 h on watching TV and using the computer at home on work days (66 % and non-work days (88 %. Adults spending ≤ 2 h/day in leisure-related screen time were less likely to permit children > 2 h/day of screen time. These associations did not differ by adult gender and parental status. Conclusions Most adults think it is appropriate to limit children’s screen time to the recommended ≤ 2 h/day but few adults themselves adhere to this screen time limit. Adults with lower screen use may be more inclined to limit children’s screen time. Strategies to reduce screen time in children may also need to target adult screen use.
Nguyen, Quang; McKinney, Jason; Johnson, Donald J; Roberts, Katherine A; Hardy, Winters R
In this proof-of-concept study, high-resolution melt curve (HRMC) analysis was investigated as a postquantification screening tool to discriminate human CSF1PO and THO1 genotypes amplified with mini-STR primers in the presence of SYBR Green or LCGreen Plus dyes. A total of 12 CSF1PO and 11 HUMTHO1 genotypes were analyzed on the LightScanner HR96 and LS-32 systems and were correctly differentiated based upon their respective melt profiles. Short STR amplicon melt curves were affected by repeat number, and single-source and mixed DNA samples were additionally differentiated by the formation of heteroduplexes. Melting curves were shown to be unique and reproducible from DNA quantities ranging from 20 to 0.4 ng and distinguished identical from nonidentical genotypes from DNA derived from different biological fluids and compromised samples. Thus, a method is described which can assess both the quantity and the possible probative value of samples without full genotyping. 2012 American Academy of Forensic Sciences. Published 2012. This article is a U.S. Government work and is in the public domain in the U.S.A.
Von Euler-Chelpin, My; Lynge, Elsebeth; Rebolj, Matejka
INTRODUCTION: There are two organised cancer screening programmes in Denmark, against cervical and breast cancers. The aim with this study was to give an overview of the available register-based research regarding these two programmes, to demonstrate the usefulness of data from the national regis...
Hiraoka, Miki; Takahashi, Hiroshi; Orimo, Hideo; Hiraoka, Miina; Ogata, Tsutomu; Azuma, Noriyuki
Purpose To evaluate the possibility of genetic involvement in retinopathy of prematurity (ROP). Although ROP is most often associated with low birthweight and low gestational age, these factors do not necessarily predict the severity of ROP. The possible involvement of other factors, including genetic variants, has been considered. Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder with clinical manifestations similar to those of ROP. Three genes involving the ...
Medina, Paul Mark B.; Swick, Lance L.; Andersen, Ryan; Blalock, Zachary; Brenman, Jay E.
Vertebrate and invertebrate dendrites are information-processing compartments that can be found on both central and peripheral neurons. Elucidating the molecular underpinnings of information processing in the nervous system ultimately requires an understanding of the genetic pathways that regulate dendrite formation and maintenance. Despite the importance of dendrite development, few forward genetic approaches have been used to analyze the latest stages of dendrite development, including the ...
Prostate cancer (CaP) is the most frequent cancer among men over 50 and its frequency increases with age. It has become a significant public health problem due to the ageing population. Epidemiologists report familial aggregation in 15 to 25% of cases and inherited susceptibility with autosomal dominant or X-linked model in 5 to 10% of cases. Clinical and biological features of familial CaP remain controversial. To perform: (1) Genetic study of familial Cap (mapping of susceptibility genes), (2) epidemiologic study (prevalence, associated cancers in the genealogy, model of transmission), and clinical study of familial CaP. (I) conducting a nationwide family collection (ProGène study) with 2+ CaP we have performed a genomewide linkage analysis and identified a predisposing locus on 1q42.2-43 named PCaP (Predisposing to Cancer of the Prostate); (II) conducting a systematic genealogic analysis of 691 CaP followed up in 3 University departments of urology (Hospitals of Brest, Paris St Louis and Nancy) we have observed: (1) 14.2% of familial and 3.6% of hereditary CaP, (2) a higher risk of breast cancer in first degree relatives of probands (CaP+) in familial CaP than in sporadic CaP and in early onset CaP (< 55 years) when compared with late onset CaP ([dG]75 years), (3) an autosomal dominant model with brother-brother dependance), (4) the lack of specific clinical or biological feature (except for early onset) in hereditary CaP when compared with sporadic CaP. (1) The mapping of a susceptibility locus will permit the cloning of a predisposing gene on 1q42.2-43, offer the possibility of genetic screening in families at risk and permit genotype/phenotype correlation studies; (2) the transmission model will improve parameteric linkage studies; (3) the lack of distinct specific clinical patterns suggest diagnostic and follow up modalities for familial and hereditary CaP similar to sporadic cancer while encouraging early screening of families at risk, given the earlier
Windy A Boyd
Full Text Available Government agencies have defined a need to reduce, refine or replace current mammalian-based bioassays with testing methods that use alternative species. Invertebrate species, such as Caenorhabditis elegans, provide an attractive option because of their short life cycles, inexpensive maintenance, and high degree of evolutionary conservation with higher eukaryotes. The C. elegans pharynx is a favorable model for studying neuromuscular function, and the effects of chemicals on neuromuscular activity, i.e., feeding. Current feeding methodologies, however, are labor intensive and only semi-quantitative.Here a high-throughput assay is described that uses flow cytometry to measure C. elegans feeding by determining the size and intestinal fluorescence of hundreds of nematodes after exposure to fluorescent-labeled microspheres. This assay was validated by quantifying fluorescence in feeding-defective C. elegans (eat mutants, and by exposing wild-type nematodes to the neuroactive compounds, serotonin and arecoline. The eat mutations previously determined to cause slow pumping rates exhibited the lowest feeding levels with our assay. Concentration-dependent increases in feeding levels after serotonin exposures were dependent on food availability, while feeding levels decreased in arecoline-exposed nematodes regardless of the presence of food. The effects of the environmental contaminants, cadmium chloride and chlorpyrifos, on wild-type C. elegans feeding were then used to demonstrate an application of the feeding assay. Cadmium exposures above 200 microM led to a sharp drop in feeding levels. Feeding of chlorpyrifos-exposed nematodes decreased in a concentration-dependent fashion with an EC(50 of 2 microM.The C. elegans fluorescence microsphere feeding assay is a rapid, reliable method for the assessment of neurotoxic effects of pharmaceutical drugs, industrial chemicals or environmental agents. This assay may also be applicable to large scale genetic or
In this thesis five molecular genetic studies on flax ( Linum usitatissimum L.) are described, of which two chapters aim to characterize the genetic structure and the amount of genetic diversity in the primary and secondary gene pool of the crop species. Three chapters describe the development of
The use of reproductive vigor descriptors in studying genetic variability in nine Tunisian faba bean ( Vicia faba L.) populations. ... The dendrogram based on Nei's genetic distance of the 9 populations using UPGMA method, show some genetic drift between populations. Key words: Faba bean, agromorphological traits, ...
breed has undergone such a metamorphosis that it no longer bears much, if any, resemblance to its European ancestor. The need for a separate genetic characterization of this distinct South African strain is therefore evident. The aim of this study was to determine the applicable non-genetic factors and to estimate genetic ...
Vernesi, Cristiano; Caramelli, David; Dupanloup, Isabelle
The origins of the Etruscans, a non-Indo-European population of preclassical Italy, are unclear. There is broad agreement that their culture developed locally, but the Etruscans' evolutionary and migrational relationships are largely unknown. In this study, we determined mitochondrial DNA sequences...... a culture but also a mitochondrial gene pool. Genetic distances and sequence comparisons show closer evolutionary relationships with the eastern Mediterranean shores for the Etruscans than for modern Italian populations. All mitochondrial lineages observed among the Etruscans appear typically European...... or West Asian, but only a few haplotypes were found to have an exact match in a modern mitochondrial database, raising new questions about the Etruscans' fate after their assimilation into the Roman state....
Abbott, Kenneth L; Nyre, Erik T; Abrahante, Juan; Ho, Yen-Yi; Isaksson Vogel, Rachel; Starr, Timothy K
Identification of cancer driver gene mutations is crucial for advancing cancer therapeutics. Due to the overwhelming number of passenger mutations in the human tumor genome, it is difficult to pinpoint causative driver genes. Using transposon mutagenesis in mice many laboratories have conducted forward genetic screens and identified thousands of candidate driver genes that are highly relevant to human cancer. Unfortunately, this information is difficult to access and utilize because it is scattered across multiple publications using different mouse genome builds and strength metrics. To improve access to these findings and facilitate meta-analyses, we developed the Candidate Cancer Gene Database (CCGD, http://ccgd-starrlab.oit.umn.edu/). The CCGD is a manually curated database containing a unified description of all identified candidate driver genes and the genomic location of transposon common insertion sites (CISs) from all currently published transposon-based screens. To demonstrate relevance to human cancer, we performed a modified gene set enrichment analysis using KEGG pathways and show that human cancer pathways are highly enriched in the database. We also used hierarchical clustering to identify pathways enriched in blood cancers compared to solid cancers. The CCGD is a novel resource available to scientists interested in the identification of genetic drivers of cancer. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Kimberling, William J; Hildebrand, Michael S; Shearer, A Eliot; Jensen, Maren L; Halder, Jennifer A; Trzupek, Karmen; Cohn, Edward S; Weleber, Richard G; Stone, Edwin M; Smith, Richard J H
Usher syndrome is a major cause of genetic deafness and blindness. The hearing loss is usually congenital and the retinitis pigmentosa is progressive and first noticed in early childhood to the middle teenage years. Its frequency may be underestimated. Newly developed molecular technologies can detect the underlying gene mutation of this disorder early in life providing estimation of its prevalence in at risk pediatric populations and laying a foundation for its incorporation as an adjunct to newborn hearing screening programs. A total of 133 children from two deaf and hard of hearing pediatric populations were genotyped first for GJB2/6 and, if negative, then for Usher syndrome. Children were scored as positive if the test revealed > or =1 pathogenic mutations in any Usher gene. Fifteen children carried pathogenic mutations in one of the Usher genes; the number of deaf and hard of hearing children carrying Usher syndrome mutations was 15/133 (11.3%). The population prevalence was estimated to be 1/6000. Usher syndrome is more prevalent than has been reported before the genome project era. Early diagnosis of Usher syndrome has important positive implications for childhood safety, educational planning, genetic counseling, and treatment. The results demonstrate that DNA testing for Usher syndrome is feasible and may be a useful addition to newborn hearing screening programs.
Full Text Available Model organisms have played an important role in the elucidation of multiple genes and cellular processes that regulate aging. In this study we utilized the budding yeast, Saccharomyces cerevisiae, in a large-scale screen for genes that function in the regulation of chronological lifespan, which is defined by the number of days that non-dividing cells remain viable. A pooled collection of viable haploid gene deletion mutants, each tagged with unique identifying DNA "bar-code" sequences was chronologically aged in liquid culture. Viable mutants in the aging population were selected at several time points and then detected using a microarray DNA hybridization technique that quantifies abundance of the barcode tags. Multiple short- and long-lived mutants were identified using this approach. Among the confirmed short-lived mutants were those defective for autophagy, indicating a key requirement for the recycling of cellular organelles in longevity. Defects in autophagy also prevented lifespan extension induced by limitation of amino acids in the growth media. Among the confirmed long-lived mutants were those defective in the highly conserved de novo purine biosynthesis pathway (the ADE genes, which ultimately produces IMP and AMP. Blocking this pathway extended lifespan to the same degree as calorie (glucose restriction. A recently discovered cell-extrinsic mechanism of chronological aging involving acetic acid secretion and toxicity was suppressed in a long-lived ade4Delta mutant and exacerbated by a short-lived atg16Delta autophagy mutant. The identification of multiple novel effectors of yeast chronological lifespan will greatly aid in the elucidation of mechanisms that cells and organisms utilize in slowing down the aging process.
Mellerup, Erling Thyge; Møller, Gert Lykke; Mondal, Pinaki
In the single locus strategy a number of genetic variants are analyzed, in order to find variants that are distributed significantly different between controls and patients. A supplementary strategy is to analyze combinations of genetic variants. A combination that is the genetic basis...... for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented...
Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.
Dey, Arup; Wall, Daniel
Upon physical contact with sibling cells, myxobacteria transiently fuse their outer membranes (OMs) and exchange OM proteins and lipids. From previous work, TraA and TraB were identified to be essential factors for OM exchange (OME) in donor and recipient cells. To define the genetic complexity of OME, we carried out a comprehensive forward genetic screen. The screen was based on the observation that Myxococcus xanthus nonmotile cells, by a Tra-dependent mechanism, block swarm expansion of motile cells when mixed. Thus, mutants defective in OME or a downstream responsive pathway were readily identified as escape flares from mixed inocula seeded on agar. This screen was surprisingly powerful, as we found >50 mutants defective in OME. Importantly, all of the mutations mapped to the traAB operon, suggesting that there may be few, if any, proteins besides TraA and TraB directly required for OME. We also found a second and phenotypically different class of mutants that exhibited wild-type OME but were defective in a responsive pathway. This pathway is postulated to control inner membrane homeostasis by covalently attaching amino acids to phospholipids. The identified proteins are homologous to the Staphylococcus aureus MprF protein, which is involved in membrane adaptation and antibiotic resistance. Interestingly, we also found that a small number of nonmotile cells were sufficient to block the swarming behavior of a large gliding-proficient population. This result suggests that an OME-derived signal could be amplified from a few nonmotile producers to act on many responder cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
A.J. Rijnsburger (Rian)
textabstract"Women with a BRCA1 or BRCA2 mutation, who have a considerable increased risk of developing breast cancer, now face the choice of intensive screening, prophylactic surgery or chemoprevention. The efficacy of the various medical options and the durability of its effects are of major
Su, Shih-Heng; Krysan, Patrick J
Mitogen-activated protein kinase cascades are conserved in all eukaryotes. In Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal abnormal phenotypes for a majority of these genes. One strategy for uncovering gene function when single-mutant lines do not produce an informative phenotype is to perform a systematic genetic interaction screen whereby double-mutants are created from a large library of single-mutant lines. Here we describe a new collection of 275 double-mutant lines derived from a library of single-mutants targeting genes related to MAP kinase signaling. To facilitate this study, we developed a high-throughput double-mutant generating pipeline using a system for growing Arabidopsis seedlings in 96-well plates. A quantitative root growth assay was used to screen for evidence of genetic interactions in this double-mutant collection. Our screen revealed four genetic interactions, all of which caused synthetic enhancement of the root growth defects observed in a MAP kinase 4 (MPK4) single-mutant line. Seeds for this double-mutant collection are publicly available through the Arabidopsis Biological Resource Center. Scientists interested in diverse biological processes can now screen this double-mutant collection under a wide range of growth conditions in order to search for additional genetic interactions that may provide new insights into MAP kinase signaling. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.
Dörries, Hans-Henno; Remus, Ivonne; Grönewald, Astrid; Grönewald, Cordt; Berghof-Jäger, Kornelia
The number of commercially available genetically modified organisms (GMOs) and therefore the diversity of possible target sequences for molecular detection techniques are constantly increasing. As a result, GMO laboratories and the food production industry currently are forced to apply many different methods to reliably test raw material and complex processed food products. Screening methods have become more and more relevant to minimize the analytical effort and to make a preselection for further analysis (e.g., specific identification or quantification of the GMO). A multiplex real-time PCR kit was developed to detect the 35S promoter of the cauliflower mosaic virus, the terminator of the nopaline synthase gene of Agrobacterium tumefaciens, the 35S promoter from the figwort mosaic virus, and the bar gene of the soil bacterium Streptomyces hygroscopicus as the most widely used sequences in GMOs. The kit contains a second assay for the detection of plant-derived DNA to control the quality of the often processed and refined sample material. Additionally, the plant-specific assay comprises a homologous internal amplification control for inhibition control. The determined limits of detection for the five assays were 10 target copies/reaction. No amplification products were observed with DNAs of 26 bacterial species, 25 yeasts, 13 molds, and 41 not genetically modified plants. The specificity of the assays was further demonstrated to be 100% by the specific amplification of DNA derived from reference material from 22 genetically modified crops. The applicability of the kit in routine laboratory use was verified by testing of 50 spiked and unspiked food products. The herein described kit represents a simple and sensitive GMO screening method for the reliable detection of multiple GMO-specific target sequences in a multiplex real-time PCR reaction.
Bell, Richard L.; Hauser, Sheketha; Rodd, Zachary A.; Liang, Tiebing; Sari, Youssef; McClintick, Jeanette; Rahman, Shafiqur; Engleman, Eric A.
The purpose of this review is to present up-to-date pharmacological, genetic and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein we sought to place the P rat’s behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this paper discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general. PMID:27055615
Sanchez Gómez, S.; Torres Tabanera, M.; Vega Bolivar, A.; Sainz Miranda, M.; Baroja Mazo, A.; Ruiz Diaz, M.; Martinez Miravete, P.; Lag Asturiano, E.; Muñoz Cacho, P.; Delgado Macias, T.
Objective: The purpose of our study was to perform a prospective assessment of the impact of a CAD system in a screen-film mammography screening program during a period of 3 years. Materials and methods: Our study was carried out on a population of 21,855 asymptomatic women (45–65 years). Mammograms were processed in a CAD system and independently interpreted by one of six radiologists. We analyzed the following parameters: sensitivity of radiologist's interpretation (without and with CAD), detection increase, recall rate and positive predictive value of biopsy, CAD's marks, radiologist's false negatives and comparative analysis of carcinomas detected and non-detected by CAD. Results: Detection rate was 4.3‰. CAD supposed an increase of 0.1‰ in detection rate and 1% in the total number of cases (p < 0.005). The impact on recall rate was not significant (0.4%) and PPV of percutaneous biopsy was unchanged by CAD (20.23%). CAD's marks were 2.7 per case and 0.7 per view. Radiologist's false negatives were 13 lesions which were initially considered as CAD's false positives. Conclusions: CAD supposed a significant increase in detection, without modifications in recall rates and PPV of biopsy. However, better results could have been achieved if radiologists had considered actionable those cases marked by CAD but initially misinterpreted.
Bal, C; Lefèvre, T; Scrivens, R; Taborelli, M
It has been observed on different machines that scintillating ceramic screens (like chromium doped alumina) are quickly damaged by low energy ion beams. These particles are completely stopped on the surface of the screens, inducing both a high local temperature increase and the electrical charging of the material. A study has been initiated to understand the limiting factors and the damage mechanisms. Several materials, ZrO2, BN and Al2O3, have been tested at CERN on LINAC3 with 4.2MeV/u lead ions. Alumina (Al2O3) is used as the reference material as it is extensively used in beam imaging systems. Boron nitride (BN) has better thermal properties than Alumina and Zirconium oxide (ZrO2). BN has in fact the advantage of increasing its electrical conductivity when heated. This contribution presents the results of the beam tests, including the post-mortem analysis of the screens and the outlook for further measurements. The strategy for the choice of the screens for the Low Energy Ion Ring (LEIR), currently under ...
Xiong, Jinghong; Muraki, Satoshi
This study investigated the relationships between thumb muscle activity and thumb operating tasks on a smartphone touch screen with one-hand posture. Six muscles in the right thumb and forearm were targeted in this study, namely adductor pollicis, flexor pollicis brevis, abductor pollicis brevis (APB), abductor pollicis longus, first dorsal interosseous (FDI) and extensor digitorum. The performance measures showed that the thumb developed fatigue rapidly when tapping on smaller buttons (diameter: 9 mm compared with 3 mm), and moved more slowly in flexion-extension than in adduction-abduction orientation. Meanwhile, the electromyography and perceived exertion values of FDI significantly increased in small button and flexion-extension tasks, while those of APB were greater in the adduction-abduction task. This study reveals that muscle effort among thumb muscles on a touch screen smartphone varies according to the task, and suggests that the use of small touch buttons should be minimised for better thumb performance.
Bowl, Michael R.; Simon, Michelle M.; Ingham, Neil J.
The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. O...
Gao, Yong-Ming; Wan, Ping
Screening markers efficiently is the foundation of mapping QTLs by composite interval mapping. Main and interaction markers distinguished, besides using background control for genetic variation, could also be used to construct intervals of two-way searching for mapping QTLs with epistasis, which can save a lot of calculation time. Therefore, the efficiency of marker screening would affect power and precision of QTL mapping. A doubled haploid population with 200 individuals and 5 chromosomes was constructed, with 50 markers evenly distributed at 10 cM space. Among a total of 6 QTLs, one was placed on chromosome I, two linked on chromosome II, and the other three linked on chromosome IV. QTL setting included additive effects and epistatic effects of additive x additive, the corresponding QTL interaction effects were set if data were collected under multiple environments. The heritability was assumed to be 0.5 if no special declaration. The power of marker screening by stepwise regression, forward regression, and three methods for random effect prediction, e.g. best linear unbiased prediction (BLUP), linear unbiased prediction (LUP) and adjusted unbiased prediction (AUP), was studied and compared through 100 Monte Carlo simulations. The results indicated that the marker screening power by stepwise regression at 0.1, 0.05 and 0.01 significant level changed from 2% to 68%, the power changed from 2% to 72% by forward regression. The larger the QTL effects, the higher the marker screening power. While the power of marker screening by three random effect prediction was very low, the maximum was only 13%. That suggested that regression methods were much better than those by using the approaches of random effect prediction to identify efficient markers flanking QTLs, and forward selection method was more simple and efficient. The results of simulation study on heritability showed that heightening of both general heritability and interaction heritability of genotype x
Madlensky, Lisa; Trepanier, Angela M; Cragun, Deborah; Lerner, Barbara; Shannon, Kristen M; Zierhut, Heather
As healthcare reimbursement is increasingly tied to value-of-service, it is critical for the genetic counselor (GC) profession to demonstrate the value added by GCs through outcomes research. We conducted a rapid systematic literature review to identify outcomes of genetic counseling. Web of Science (including PubMed) and CINAHL databases were systematically searched to identify articles meeting the following criteria: 1) measures were assessed before and after genetic counseling (pre-post design) or comparisons were made between a GC group vs. a non-GC group (comparative cohort design); 2) genetic counseling outcomes could be assessed independently of genetic testing outcomes, and 3) genetic counseling was conducted by masters-level genetic counselors, or non-physician providers. Twenty-three papers met the inclusion criteria. The majority of studies were in the cancer genetic setting and the most commonly measured outcomes included knowledge, anxiety or distress, satisfaction, perceived risk, genetic testing (intentions or receipt), health behaviors, and decisional conflict. Results suggest that genetic counseling can lead to increased knowledge, perceived personal control, positive health behaviors, and improved risk perception accuracy as well as decreases in anxiety, cancer-related worry, and decisional conflict. However, further studies are needed to evaluate a wider array of outcomes in more diverse genetic counseling settings.
Nicholas Le Maitre
Phylogenetic trees were created for leaf and stem rust pathotypes. Field isolates of ... Key words: Prevalence, microsatellite, amplified fragment length polymorphisms (AFLP), phylogeny, Puccinia. INTRODUCTION. Puccinia triticina Eriks ..... Genetic distances and reconstruction phylogenetic trees from microsatellite DNA.
Shea, Nicole A.; Duncan, Ravit Golan; Stephenson, Celeste
Genetics literacy is becoming increasingly important as advancements in our application of genetic technologies such as stem cell research, cloning, and genetic screening become more prevalent. Very few studies examine how genetics literacy is applied when reasoning about authentic genetic dilemmas. However, there is evidence that situational…
Full Text Available Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from DNA sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that SNPs within the binding sites of the transcriptional repressor REST alter the degree of repression of target genes. Given that changes in the effective concentration of REST contribute to several pathologies-various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation-these SNPs should alter disease-susceptibility in carriers. We devised a strategy to identify SNPs that affect the recruitment of REST to target genes through the alteration of its DNA recognition element, the RE1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic RE1 sequences with robust and statistically significant differences of affinity between alleles. These SNPs have a considerable effect on the the functional recruitment of REST to DNA in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in RE1 affinity. Amongst the targets of polymorphic RE1 elements are important disease genes including NPPA, PTPRT, and CDH4. Thus, considerable genetic variation exists in the DNA motifs that connect gene regulatory networks. Recently available ChIP-seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism.
Johnson, Rory; Richter, Nadine; Bogu, Gireesh K.; Bhinge, Akshay; Teng, Siaw Wei; Choo, Siew Hua; Andrieux, Lise O.; de Benedictis, Cinzia; Jauch, Ralf; Stanton, Lawrence W.
Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from DNA sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that SNPs within the binding sites of the transcriptional repressor REST alter the degree of repression of target genes. Given that changes in the effective concentration of REST contribute to several pathologies—various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation—these SNPs should alter disease-susceptibility in carriers. We devised a strategy to identify SNPs that affect the recruitment of REST to target genes through the alteration of its DNA recognition element, the RE1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic RE1 sequences with robust and statistically significant differences of affinity between alleles. These SNPs have a considerable effect on the the functional recruitment of REST to DNA in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in RE1 affinity. Amongst the targets of polymorphic RE1 elements are important disease genes including NPPA, PTPRT, and CDH4. Thus, considerable genetic variation exists in the DNA motifs that connect gene regulatory networks. Recently available ChIP–seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism. PMID:22496669
Fusco, Dahlene N; Brisac, Cynthia; John, Sinu P; Huang, Yi-Wen; Chin, Christopher R; Xie, Tiao; Zhao, Hong; Jilg, Nikolaus; Zhang, Leiliang; Chevaliez, Stephane; Wambua, Daniel; Lin, Wenyu; Peng, Lee; Chung, Raymond T; Brass, Abraham L
Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease. Interferon-α (IFNα) is an important component of anti-HCV therapy; it up-regulates transcription of IFN-stimulated genes, many of which have been investigated for their antiviral effects. However, all of the genes required for the antiviral function of IFNα (IFN effector genes [IEGs]) are not known. IEGs include not only IFN-stimulated genes, but other nontranscriptionally induced genes that are required for the antiviral effect of IFNα. In contrast to candidate approaches based on analyses of messenger RNA (mRNA) expression, identification of IEGs requires a broad functional approach. We performed an unbiased genome-wide small interfering RNA screen to identify IEGs that inhibit HCV. Huh7.5.1 hepatoma cells were transfected with small interfering RNAs incubated with IFNα and then infected with JFH1 HCV. Cells were stained using HCV core antibody, imaged, and analyzed to determine the percent infection. Candidate IEGs detected in the screen were validated and analyzed further. The screen identified 120 previously unreported IEGs. From these, we more fully evaluated the following: asparagine-linked glycosylation 10 homolog (yeast, α-1,2-glucosyltransferase); butyrylcholinesterase; dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2); glucokinase (hexokinase 4) regulator; guanylate cyclase 1, soluble, β 3; MYST histone acetyltransferase 1; protein phosphatase 3 (formerly 2B), catalytic subunit, β isoform; peroxisomal proliferator-activated receptor-γ-DBD-interacting protein 1; and solute carrier family 27 (fatty acid transporter), member 2; and demonstrated that they enabled IFNα-mediated suppression of HCV at multiple steps of its life cycle. Expression of these genes had more potent effects against flaviviridae because a subset was required for IFNα to suppress dengue virus but not influenza A virus. In addition, many of the host genes detected in this
Havndrup, Ole; Christiansen, Michael; Stoevring, Birgitte
AIMS: Fabry disease, an X-linked storage disorder caused by defective lysosomal enzyme alpha-galactosidase A activity, may resemble sarcomere-gene-associated hypertrophic cardiomyopathy (HCM). The 'cardiac variant' of Fabry disease which only affects the heart may be missed unless specifically te...... therapy, supports systematic testing for Fabry disease. Enzyme measurements are sufficient in men, but genetic testing is needed in women....
Rossing, Maria; Albrechtsen, Anders; Skytte, Anne-Bine
Pathogenic germline mutations in the folliculin (FLCN) tumor suppressor gene predispose to Birt-Hogg-Dubé (BHD) syndrome, a rare disease characterized by the development of cutaneous hamartomas (fibrofolliculomas), multiple lung cysts, spontaneous pneumothoraces and renal cell cancer. In this stu...... understanding of BHD syndrome and management of BHD patients.Journal of Human Genetics advance online publication, 13 October 2016; doi:10.1038/jhg.2016.118....
factories vary largely, including industrial production of valuable compounds for biofuels, polymer synthesis and food, cosmetic and pharmaceutical industry. The improvement of computational and biochemical tools has revolutionized the synthesis of novel modified microbial strains, opening up new......The importance of metabolic engineering has been growing over the last decades, establishing the use of genetically modified microbial strains for overproduction of metabolites at industrial scale as an innovative, convenient and biosustainable method. Nowadays, application areas of microbial...
Champagne , and Pierre Drapeau. 25th international symposium on ALS/MND (5-7 December 2014) Patten SA, Vaccaro A, Drapeau P, Kabashi E, Parker JA...transgenic mice produced with TDP- 43 genomic fragments. Brain 134, 2610-2626 (2011). 6 Kabashi, E., Champagne , N., Brustein, E. & Drapeau, P. In the...swim of things: recent insights to neurogenetic disorders from zebrafish. Trends Genet 26, 373-381 (2010). 7 Kabashi, E., Brustein, E., Champagne , N
red. Chlo= Chlorprothixene hydrochloride; Amo= Amoxapine; Mians = Mianserine hydrochloride; Pizo= Pizotifen malate; Pimet= Pimethixene maleate; Cloz...lobar degeneration in transgenic mice produced with TDP-43 genomic fragments. Brain. 32. Li Y, Ray P, Rao EJ, Shi C, Guo W, et al. (2010) A Drosophila...2008) Sirtuin Inhibition Protects from the Polyalanine Muscular Dystrophy Protein PABPN1. Hum Mol Genet. 36. Wang J, Farr GW, Hall DH, Li F, Furtak
Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén's studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl's studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker's studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts. Copyright © 2016 by
Sills, E Scott; Anderson, Robert E; McCaffrey, Mary; Li, Xiang; Arrach, Nabil; Wood, Samuel H
Preimplantation genetic screening (PGS) is a component of IVF entailing selection of an embryo for transfer on the basis of chromosomal normalcy. If PGS were integrated with single embryo transfer (SET) in a surrogacy setting, this approach could improve pregnancy rates, minimize miscarriage risk, and limit multiple gestations. Even without PGS, pregnancy rates for IVF surrogacy cases are generally satisfactory, especially when treatment utilizes embryos derived from young oocytes and transferred to a healthy surrogate. However, there could be a more general role for PGS in surrogacy, since background aneuploidy in embryos remains a major factor driving implantation failure and miscarriage for all infertility patients. At present, the proportion of IVF cases involving GS is limited, while the number of IVF patients requesting PGS appears to be increasing. In this report, the relevance of PGS for surrogacy in the rapidly changing field of assisted fertility medicine is discussed. © 2015 Wiley Periodicals, Inc.
Full Text Available Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that ∼50% of the chaperones are essential in Drosophila. Knocking down these genes in eyes revealed that ∼30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry, and robust behavioral assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data present the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified a new set of chaperones that regulate eye and NMJ morphogenesis. The outcome of the screen reported here provides a useful resource for further elucidating the role of individual chaperones in Drosophila eye morphogenesis and synaptic development.
Klompenhouwer, E. G.; Duijm, L. E. M.; Voogd, A. C.; den Heeten, G. J.; Nederend, J.; Jansen, F. H.; Broeders, M. J. M.
Substantial inter-observer variability in screening mammography interpretation has been reported at single reading. However, screening results of pairs of screening radiologists have not yet been published. We determined variations in screening performances among pairs of screening radiologists at
Debra A O'Leary
Full Text Available One therapeutic approach to Duchenne Muscular Dystrophy (DMD recently entering clinical trials aims to convert DMD phenotypes to that of a milder disease variant, Becker Muscular Dystrophy (BMD, by employing antisense oligonucleotides (AONs targeting splice sites, to induce exon skipping and restore partial dystrophin function. In order to search for small molecule and genetic modulators of AON-dependent and independent exon skipping, we screened approximately 10,000 known small molecule drugs, >17,000 cDNA clones, and >2,000 kinase- targeted siRNAs against a 5.6 kb luciferase minigene construct, encompassing exon 71 to exon 73 of human dystrophin. As a result, we identified several enhancers of exon skipping, acting on both the reporter construct as well as endogenous dystrophin in mdx cells. Multiple mechanisms of action were identified, including histone deacetylase inhibition, tubulin modulation and pre-mRNA processing. Among others, the nucleolar protein NOL8 and staufen RNA binding protein homolog 2 (Stau2 were found to induce endogenous exon skipping in mdx cells in an AON-dependent fashion. An unexpected but recurrent theme observed in our screening efforts was the apparent link between the inhibition of cell cycle progression and the induction of exon skipping.
Meeske, Alexander J; Rodrigues, Christopher D A; Brady, Jacqueline; Lim, Hoong Chuin; Bernhardt, Thomas G; Rudner, David Z
The differentiation of the bacterium Bacillus subtilis into a dormant spore is among the most well-characterized developmental pathways in biology. Classical genetic screens performed over the past half century identified scores of factors involved in every step of this morphological process. More recently, transcriptional profiling uncovered additional sporulation-induced genes required for successful spore development. Here, we used transposon-sequencing (Tn-seq) to assess whether there were any sporulation genes left to be discovered. Our screen identified 133 out of the 148 genes with known sporulation defects. Surprisingly, we discovered 24 additional genes that had not been previously implicated in spore formation. To investigate their functions, we used fluorescence microscopy to survey early, middle, and late stages of differentiation of null mutants from the B. subtilis ordered knockout collection. This analysis identified mutants that are delayed in the initiation of sporulation, defective in membrane remodeling, and impaired in spore maturation. Several mutants had novel sporulation phenotypes. We performed in-depth characterization of two new factors that participate in cell-cell signaling pathways during sporulation. One (SpoIIT) functions in the activation of σE in the mother cell; the other (SpoIIIL) is required for σG activity in the forespore. Our analysis also revealed that as many as 36 sporulation-induced genes with no previously reported mutant phenotypes are required for timely spore maturation. Finally, we discovered a large set of transposon insertions that trigger premature initiation of sporulation. Our results highlight the power of Tn-seq for the discovery of new genes and novel pathways in sporulation and, combined with the recently completed null mutant collection, open the door for similar screens in other, less well-characterized processes.
Brady, Jacqueline; Lim, Hoong Chuin; Bernhardt, Thomas G.; Rudner, David Z.
The differentiation of the bacterium Bacillus subtilis into a dormant spore is among the most well-characterized developmental pathways in biology. Classical genetic screens performed over the past half century identified scores of factors involved in every step of this morphological process. More recently, transcriptional profiling uncovered additional sporulation-induced genes required for successful spore development. Here, we used transposon-sequencing (Tn-seq) to assess whether there were any sporulation genes left to be discovered. Our screen identified 133 out of the 148 genes with known sporulation defects. Surprisingly, we discovered 24 additional genes that had not been previously implicated in spore formation. To investigate their functions, we used fluorescence microscopy to survey early, middle, and late stages of differentiation of null mutants from the B. subtilis ordered knockout collection. This analysis identified mutants that are delayed in the initiation of sporulation, defective in membrane remodeling, and impaired in spore maturation. Several mutants had novel sporulation phenotypes. We performed in-depth characterization of two new factors that participate in cell–cell signaling pathways during sporulation. One (SpoIIT) functions in the activation of σE in the mother cell; the other (SpoIIIL) is required for σG activity in the forespore. Our analysis also revealed that as many as 36 sporulation-induced genes with no previously reported mutant phenotypes are required for timely spore maturation. Finally, we discovered a large set of transposon insertions that trigger premature initiation of sporulation. Our results highlight the power of Tn-seq for the discovery of new genes and novel pathways in sporulation and, combined with the recently completed null mutant collection, open the door for similar screens in other, less well-characterized processes. PMID:26735940
Most land plants possess the capacity to protect themselves from UV light, and do so by producing pigments that absorb efficiently in the UV-A and UV-B regions of the spectrum while allowing transmission of nearly all photosynthetically useful wavelengths. These UV-absorbing pigments are mainly phenylpropanoids and flavonoids. This chapter summarizes current understanding of the mechanism of UV protection in higher land plants, evaluates the information available from lower land plants and their green-algal relatives, and then considers the possible evolutionary origins of this use of chemical filters for selectively screening UV light from solar radiation. It is proposed that photo control over the biosynthesis of UV-absorbing phenylpropanoids and flavonoids may have evolved in concert with the evolution of the high biosynthetic activity necessary for UV protection. The toxicity of phenylpropanoids and flavonoids has been postulated to have been a barrier to the evolution of an effective chemical UV screen, and that some means for sequestering these compounds and/or for controlling their synthesis probably evolved prior to, or in concert with, the evolution of high rates of biosynthesis. The original photoreceptor and signal transduction system is speculated to have been based on photo isomerization of a phenylpropanoid ester and a pre-existing product feedback mechanism for controlling phenylpropanoid biosynthesis. Understanding the original mechanism for photo control of the chemical UV screen of land plants could be valuable for understanding the adaptability of extant land plants to rising levels of solar UV-B radiation and may suggest genetic strategies for engineering improved UV tolerance in crop plants. (author)
Full Text Available Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.
Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5–10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci – TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2 that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt and VAP(P58S, but in a contrasting manner. Reversal of VAP(P58S bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease.
Deivasigamani, Senthilkumar; Verma, Hemant Kumar; Ueda, Ryu; Ratnaparkhi, Anuradha; Ratnaparkhi, Girish S
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5-10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci - TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S) expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2) that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt) expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt) and VAP(P58S), but in a contrasting manner. Reversal of VAP(P58S) bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S) expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease. © 2014. Published by The Company of Biologists Ltd.
Maurer, H.J.; Goos, F.
1) Different types of screens and X-ray films have been investigated using a Kodak mamma-phantom I.T.O. 745 and compared with conventional non screen industrial film radiography. 2) Dosisreduction by using screens depends on the used film/screen system. It is possible to reach a relation of 1:10. 3) The information depends on type of screen and of type of film. Therefore, it is possible to reach the information of non screen industrial film radiographs. 4) A suitable film/screen system allows without loss of any diagnostic information to replace non screen industrial films needing a high exposure dosis by a film/screen system needing decreased dosis. (orig.) [de
Jørgensen, Karsten J; Zahl, Per-Henrik; Gøtzsche, Peter C
% of the Danish population has been offered organised mammography screening over a long time-period. METHODS: We collected incidence rates of carcinoma in situ and invasive breast cancer in areas with and without screening over 13 years with screening (1991-2003), and 20 years before its introduction (1971...... an overdiagnosis of 35% when we compared unadjusted incidence rates for the screened and non-screened areas, but after compensating for a small decline in incidence in older, previously screened women. Our adjusted Poisson regression analysis indicated a relative risk of 1.40 (95% CI: 1.35-1.45) for the whole...... screening period, and a potential compensatory drop in older women of 0.90 (95% CI: 0.88-0.96), yielding an overdiagnosis of 33%, which we consider the most reliable estimate. The drop in previously screened women was only present in one of the two screened regions and was small in absolute numbers...
Te Meerman, Sanne; Batstra, Laura; Hoekstra, Rink; Grietens, Hans
Academic study books are essential assets for disseminating knowledge about ADHD to future healthcare professionals. This study examined if they are balanced with regard to genetics. We selected and analyzed study books (N=43) used in (pre) master's programmes at 10 universities in the Netherlands. Because the mere behaviourally informed quantitative genetics give a much higher effect size of the genetic involvement in ADHD, it is important that study books contrast these findings with molecular genetics' outcomes. The latter studies use real genetic data, and their low effect sizes expose the potential weaknesses of quantitative genetics, like underestimating the involvement of the environment. Only a quarter of books mention both effect sizes and contrast these findings, while another quarter does not discuss any effect size. Most importantly, however, roughly half of the books in our sample mention only the effect sizes from quantitative genetic studies without addressing the low explained variance of molecular genetic studies. This may confuse readers by suggesting that the weakly associated genes support the quite spectacular, but potentially flawed estimates of twin, family and adoption studies, while they actually contradict them.
Full Text Available Anchorage-independent proliferation is a hallmark of oncogenic transformation and is thought to be conducive to proliferation of cancer cells away from their site of origin. We have previously reported that primary Schwann cells expressing the SV40 Large T antigen (LT are not fully transformed in that they maintain a strict requirement for attachment, requiring a further genetic change, such as oncogenic Ras, to gain anchorage-independence. Using the LT-expressing cells, we performed a genetic screen for anchorage-independent proliferation and identified Sensory and Motor Neuron Derived Factor (SMDF, a transmembrane class III isoform of Neuregulin 1. In contrast to oncogenic Ras, SMDF induced enhanced proliferation in normal primary Schwann cells but did not trigger cellular senescence. In cooperation with LT, SMDF drove anchorage-independent proliferation, loss of contact inhibition and tumourigenicity. This transforming ability was shared with membrane-bound class III but not secreted class I isoforms of Neuregulin, indicating a distinct mechanism of action. Importantly, we show that despite being membrane-bound signalling molecules, class III neuregulins transform via a cell intrinsic mechanism, as a result of constitutive, elevated levels of ErbB signalling at high cell density and in anchorage-free conditions. This novel transforming mechanism may provide new targets for cancer therapy.
Covassin, L D; Siekmann, A F; Kacergis, M C; Laver, E; Moore, J C; Villefranc, J A; Weinstein, B M; Lawson, N D
In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.
Kortegaard, Hanne E; Eriksen, Thomas; Baelum, Vibeke
It has been shown that the prevalence of both clinical attachment loss (CAL) ≥1 mm and pocket probing depth (PPD) ≥4 mm is relatively high even in younger dogs, but also that only a minority of the dogs have such clinical signs of periodontal disease (PD) in more than a few teeth. Hence, a minority of dogs carry the major PD burden. These epidemiological features suggest that screening for PD in larger groups of dogs, allowing for rapid assessment of treatment planning, or for the selection of dogs with or without PD prior to be included in experimental trials, should be possible. CAL is the central variable in assessing PD extent and severity while PPD is the central variable used in treatment planning which make these two variables obvious in a screening protocol with the dual aim of disease identification and treatment planning. The main purpose of the present study in 98 laboratory Beagle dogs was to construct a fast, simple and accurate screening tool, which is highly sensitive for the identification of dogs with PD. Examination of the maxillary P4, P3, P2, I1 and C would, in this population, result in the identification of 85.5% of all dogs and 96% of all teeth positive for CAL ≥1 mm, and 58.9% of all dogs and 82.1% of all teeth positive for PD ≥4 mm. Examination of tooth pairs, all C's, maxillary I2, M2 and the mandibular P4 would, in this population result in identification of 92.9% of all dogs and 97.3% of all teeth positive for PD ≥4 mm, and 65.5% of all dogs and 83.2% of all teeth positive for CAL ≥1 mm. The results presented here only pertain to the present study population. This screening protocol is suitable for examination of larger groups of laboratory Beagle dogs for PD and our findings indicate that diseased dogs are identified with a high degree of sensitivity. Before this screening can be used in clinical practice, it has to be validated in breeds other than Beagle dogs and in populations with larger age variation.
Molina Silvia M.G.
Full Text Available Aiming at contributing to technological improvements in plant fiber processing methods, this paper reports research work on the obtainment of more efficient pectinase-producing fungi strains. More specifically, this work reports the analysis of 18 strains of filamentous fungi, with the purpose of obtaining enzymes for textile fibers degumming. The strains were evaluated for production of pectinolytic enzymes under several growth conditions (culture medium and growth temperature. Production of pectinases was measured by an enzymatic index (EI in solid pectin medium. Among the tested strains, Penicillium chrysogenum IFO 4626 (Q 176 showed the best performance. Genetic improvement of this strain was carried out to increase its pectinase production, while keeping cellulase activity down to a negligible level, since cellulases are known to decrease the resistance of the fiber. Variability was induced through several cycles of mutation and selection by exposing conidea to ultra-violet light (UV. We selected 39 out of 390 isolated colonies. Resulting mutants produced nine times more pectin lyase (PL than the original strain in terms of PL specific activity, and five times more in terms of PL activity (i.e. mmoles liberated per minute of reaction per mL of medium. Periodically, mutant performance was evaluated in solid pectin medium. Genetic stability was maintained for four years after isolation.
Mycobacterium avium restriction fragment lenght polymorphism-IS IS1245 and the simple double repetitive element polymerase chain reaction typing method to screen genetic diversity in Brazilian strains
Patrícia Carvalho de Sequeira
Full Text Available Simple double repetitive element polymerase chain reaction (MaDRE-PCR and Pvu II-IS1245 restriction fragment length polymorphism (RFLP typing methods were used to type 41 Mycobacterium avium isolates obtained from 14 Aids inpatients and 10 environment and animals specimens identified among 53 mycobacteria isolated from 237 food, chicken, and pig. All environmental and animals strains showed orphan patterns by both methods. By MaDRE-PCR four patients, with multiple isolates, showed different patterns, suggesting polyclonal infection that was confirmed by RFLP in two of them. This first evaluation of MaDRE-PCR on Brazilian M. avium strains demonstrated that the method seems to be useful as simple and less expensive typing method for screening genetic diversity in M. avium strains on selected epidemiological studies, although with limitation on analysis identical patterns except for one band.
Looking in detail at the composition of stars with ESO's VLT, astronomers are providing a fresh look at the history of our home galaxy, the Milky Way. They reveal that the central part of our Galaxy formed not only very quickly but also independently of the rest. "For the first time, we have clearly established a 'genetic difference' between stars in the disc and the bulge of our Galaxy," said Manuela Zoccali, lead author of the paper presenting the results in the journal Astronomy and Astrophysics . "We infer from this that the bulge must have formed more rapidly than the disc, probably in less than a billion years and when the Universe was still very young." ESO PR Photo 34a/06 ESO PR Photo 34a/06 The Field around Baade's Window The Milky Way is a spiral galaxy, having pinwheel-shaped arms of gas, dust, and stars lying in a flattened disc, and extending directly out from a spherical nucleus of stars in the central region. The spherical nucleus is called a bulge, because it bulges out from the disc. While the disc of our Galaxy is made up of stars of all ages, the bulge contains old stars dating from the time the galaxy formed, more than 10 billion years ago. Thus, studying the bulge allows astronomers to know more about how our Galaxy formed. To do this, an international team of astronomers  analysed in detail the chemical composition of 50 giant stars in four different areas of the sky towards the Galactic bulge. They made use of the FLAMES/UVES spectrograph on ESO's Very Large Telescope to obtain high-resolution spectra. The chemical composition of stars carries the signature of the enrichment processes undergone by the interstellar matter up to the moment of their formation. It depends on the previous history of star formation and can thus be used to infer whether there is a 'genetic link' between different stellar groups. In particular, comparison between the abundance of oxygen and iron in stars is very illustrative. Oxygen is predominantly produced in
Full Text Available Prevention of Hemoglobinopathies has developed around the world based upon the experience done in pioneering endemic countries and is now facing a new phase in non-endemic areas with a recent immigration history. We describe two situations, taking Latium (central Italy and The Netherlands as two models for endemic and non-endemic countries both confronted with a large multi-ethnic immigrant society. We present prevention results and discuss aspects such as local knowledge and organization. We illustrate the importance of issues like information, carrier diagnostics, screening, counseling and prenatal diagnosis in particular situation of contrasting interest an different ethical opinions. We conclude by underlining the importance of implementing primary prevention at the European level, based upon better information, diagnostics and counseling.
Carlos Bernard M. Cerqueira-Silva
Full Text Available Despite the ecological and economic importance of passion fruit (Passiflora spp., molecular markers have only recently been utilized in genetic studies of this genus. In addition, both basic genetic researches related to population studies and pre-breeding programs of passion fruit remain scarce for most Passiflora species. Considering the number of Passiflora species and the increasing use of these species as a resource for ornamental, medicinal, and food purposes, the aims of this review are the following: (i to present the current condition of the passion fruit crop; (ii to quantify the applications and effects of using molecular markers in studies of Passiflora; (iii to present the contributions of genetic engineering for passion fruit culture; and (iv to discuss the progress and perspectives of this research. Thus, the present review aims to summarize and discuss the relationship between historical and current progress on the culture, breeding, and molecular genetics of passion fruit.
Wang, Hao; Liu, Ning; Xi, Lijun; Rong, Xiaoying; Ruan, Jisheng; Huang, Ying
Polyether ionophores are a unique class of polyketides with broad-spectrum activity and outstanding potency for the control of drug-resistant bacteria and parasites, and they are produced exclusively by actinomycetes. A special epoxidase gene encoding a critical tailoring enzyme involved in the biosynthesis of these compounds has been found in all five of the complete gene clusters of polyether ionophores published so far. To detect potential producer strains of these antibiotics, a pair of degenerate primers was designed according to the conserved regions of the five known polyether epoxidases. A total of 44 putative polyether epoxidase gene-positive strains were obtained by the PCR-based screening of 1,068 actinomycetes isolated from eight different habitats and 236 reference strains encompassing eight major families of Actinomycetales. The isolates spanned a wide taxonomic diversity based on 16S rRNA gene analysis, and actinomycetes isolated from acidic soils seemed to be a promising source of polyether ionophores. Four genera were detected to contain putative polyether epoxidases, including Micromonospora, which has not previously been reported to produce polyether ionophores. The designed primers also detected putative epoxidase genes from diverse known producer strains that produce polyether ionophores unrelated to the five published gene clusters. Moreover, phylogenetic and chemical analyses showed a strong correlation between the sequence of polyether epoxidases and the structure of encoded polyethers. Thirteen positive isolates were proven to be polyether ionophore producers as expected, and two new analogues were found. These results demonstrate the feasibility of using this epoxidase gene screening strategy to aid the rapid identification of known products and the discovery of unknown polyethers in actinomycetes.
Wang, Hao; Liu, Ning; Xi, Lijun; Rong, Xiaoying; Ruan, Jisheng; Huang, Ying
Polyether ionophores are a unique class of polyketides with broad-spectrum activity and outstanding potency for the control of drug-resistant bacteria and parasites, and they are produced exclusively by actinomycetes. A special epoxidase gene encoding a critical tailoring enzyme involved in the biosynthesis of these compounds has been found in all five of the complete gene clusters of polyether ionophores published so far. To detect potential producer strains of these antibiotics, a pair of degenerate primers was designed according to the conserved regions of the five known polyether epoxidases. A total of 44 putative polyether epoxidase gene-positive strains were obtained by the PCR-based screening of 1,068 actinomycetes isolated from eight different habitats and 236 reference strains encompassing eight major families of Actinomycetales. The isolates spanned a wide taxonomic diversity based on 16S rRNA gene analysis, and actinomycetes isolated from acidic soils seemed to be a promising source of polyether ionophores. Four genera were detected to contain putative polyether epoxidases, including Micromonospora, which has not previously been reported to produce polyether ionophores. The designed primers also detected putative epoxidase genes from diverse known producer strains that produce polyether ionophores unrelated to the five published gene clusters. Moreover, phylogenetic and chemical analyses showed a strong correlation between the sequence of polyether epoxidases and the structure of encoded polyethers. Thirteen positive isolates were proven to be polyether ionophore producers as expected, and two new analogues were found. These results demonstrate the feasibility of using this epoxidase gene screening strategy to aid the rapid identification of known products and the discovery of unknown polyethers in actinomycetes. PMID:21421776
Full-field digital mammography (FFDM) has several potential benefits as compared with screen-film mammography (SFM) in mammography screening. Digital technology also opens for implementation of advanced applications, including computer-aided detection (CAD) and tomosynthesis. Phantom studies and experimental clinical studies have shown that FFDM is equal or slightly superior to SFM for detection and characterization of mammographic abnormalities. Despite obvious advantages, the conversion to digital mammography has been slower than anticipated, and not only due to higher costs. Until very recently, some countries did not even permit the use of digital mammography in breast cancer screening. The reason for this reluctant attitude was concern about lower spatial resolution and about using soft-copy reading. Furthermore, there was a lack of data supporting improved diagnostic accuracy using FFDM in a screening setting, since two pioneer trials both showed nonsignificantly lower cancer detection rate at FFDM. The 10 studies comparing FFDM and SFM in mammography screening published so far have shown divergent and rather conflicting results. Nevertheless, there is a rapid conversion to digital mammography in breast cancer screening in many western countries. The aim of this article is to give an updated review of these studies, discuss the conflicting findings, and draw some conclusions from the results
Bušić, Mladen; Bjeloš, Mirjana; Petrovečki, Mladen; Kuzmanović Elabjer, Biljana; Bosnar, Damir; Ramić, Senad; Miletić, Daliborka; Andrijašević, Lidija; Kondža Krstonijević, Edita; Jakovljević, Vid; Bišćan Tvrdi, Ana; Predović, Jurica; Kokot, Antonio; Bišćan, Filip; Kovačević Ljubić, Mirna; Motušić Aras, Ranka
To present and evaluate a new screening protocol for amblyopia in preschool children. Zagreb Amblyopia Preschool Screening (ZAPS) study protocol performed screening for amblyopia by near and distance visual acuity (VA) testing of 15 648 children aged 48-54 months attending kindergartens in the City of Zagreb County between September 2011 and June 2014 using Lea Symbols in lines test. If VA in either eye was >0.1 logMAR, the child was re-tested, if failed at re-test, the child was referred to comprehensive eye examination at the Eye Clinic. 78.04% of children passed the screening test. Estimated prevalence of amblyopia was 8.08%. Testability, sensitivity, and specificity of the ZAPS study protocol were 99.19%, 100.00%, and 96.68% respectively. The ZAPS study used the most discriminative VA test with optotypes in line as they do not underestimate amblyopia. The estimated prevalence of amblyopia was considerably higher than reported elsewhere. To the best of our knowledge, the ZAPS study protocol reached the highest sensitivity and specificity when evaluating diagnostic accuracy of VA tests for screening. The pass level defined at ≤0.1 logMAR for 4-year-old children, using Lea Symbols in lines missed no amblyopia cases, advocating that both near and distance VA testing should be performed when screening for amblyopia.
... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...
... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...
Twisk, Moniek; Haadsma, Maaike L.; van der Veen, Fulco; Repping, Sjoerd; Mastenbroek, Sebastiaan; Heineman, Maas-Jan; Bossuyt, Patrick M. M.; Korevaar, Johanna C.
Objective: Although the primary goal of preimplantation genetic screening (PGS) is to increase pregnancy rates in women undergoing IVF/intracytoplasmic sperm injection treatment, it has been suggested that it may also be used as an alternative to prenatal testing for Down syndrome. Design: Trade-off
Twisk, Moniek; Haadsma, Maaike L.; van der Veen, Fulco; Repping, Sjoerd; Mastenbroek, Sebastiaan; Heineman, Maas-Jan; Bossuyt, Patrick M. M.; Korevaar, Johanna C.
Objective: Although the primary goal of preimplantation genetic screening (PGS) is to increase pregnancy rates in women undergoing IVF/intracytoplasmic sperm injection treatment, it has been suggested that it may also be used as an alternative to prenatal testing for Down syndrome. Design: Trade-off
Evans, Austin L.; Joyce, Martin
The present sensitivity study of design variable effects on the performance of a monogroove-with-screen heat pipe obtains performance curves for maximum heat-transfer rates vs. operating temperatures by means of a computer code; performance projections for both 1-g and zero-g conditions are obtainable. The variables in question were liquid and vapor channel design, wall groove design, and the number of feed lines in the evaporator and condenser. The effect on performance of three different working fluids, namely ammonia, methanol, and water, were also determined. Greatest sensitivity was to changes in liquid and vapor channel diameters.
Pavlish, Carol L; Hellyer, Joan Henriksen; Brown-Saltzman, Katherine; Miers, Anne G; Squire, Karina
Ethical conflicts, often leading to poor teamwork and moral distress, are very challenging to patients, patients' families, and health care providers. A proactive approach to ethical conflicts may improve patient care outcomes. To examine acceptability and feasibility of an ethics screening and early intervention tool for use by nurses caring for critically ill patients. Twenty-eight nurses in 2 medical centers applied the ethics screening tool to 55 patient situations. Nurses assessed situations for risk factors and early indicators of ethical conflicts and analyzed level of risk. At study completion, nurses participated in focus group discussions about the tool's benefits and challenges. Frequency counts were performed on risk factors and early indicators of ethical conflicts. Content analysis was used on written explanations regarding high-, medium-, and low-risk situations and on focus group data. Older patients with multiple comorbid conditions and aggressive treatments were frequently assessed to be at risk for ethical conflicts. Nurses who witnessed patients' suffering and deterioration were likely to initiate the screening process. The most prominent family risk factors included unrealistic expectations and adamancy about treatment. The most prominent early indicators were signs of patients' suffering, unrealistic expectations, and providers' own moral distress. High-risk situations averaged a greater number of risk factors and early indicators than did medium- and low-risk situations. Certain risk factors featured prominently in high-risk situations. A phenomenon of shared suffering emerged from the study and signifies the importance of relational strategies such as routine family conferences and ethics consultation. ©2015 American Association of Critical-Care Nurses.
Petersen, Andrea K; Cheung, Sau Wai; Smith, Janice L; Bi, Weimin; Ward, Patricia A; Peacock, Sandra; Braxton, Alicia; Van Den Veyver, Ignatia B; Breman, Amy M
Since its debut in 2011, cell-free fetal DNA screening has undergone rapid expansion with respect to both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this screening tool, both for the originally included common autosomal and sex-chromosomal aneuploidies as well as the more recently added chromosomal microdeletion syndromes, have lagged behind. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations of this screening tool to inform pre- and posttest counseling, pre/perinatal decision making, and medical risk assessment/management. The objective of this study was to determine the positive predictive value and false-positive rates for different chromosomal abnormalities identified by cell-free fetal DNA screening using a large data set of diagnostic testing results on invasive samples submitted to the laboratory for confirmatory studies. We tested 712 patient samples sent to our laboratory to confirm a cell-free fetal DNA screening result, indicating high risk for a chromosome abnormality. We compiled data from all cases in which the indication for confirmatory testing was a positive cell-free fetal DNA screen, including the common trisomies, sex chromosomal aneuploidies, microdeletion syndromes, and other large genome-wide copy number abnormalities. Testing modalities included fluorescence in situ hybridization, G-banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples. Positive predictive values and false-positive rates were calculated from tabulated data. The positive predictive values for trisomy 13, 18, and 21 were consistent with previous reports at 45%, 76%, and 84%, respectively. For the microdeletion syndrome regions, positive predictive values ranged from 0% for detection of Cri-du-Chat syndrome and Prader-Willi/Angelman syndrome to 14% for 1p36 deletion
Full Text Available The determination of the scientific basis of heredity within the last two decades and the verification of the principal conclusions in many different plants and animals has made possible the application of analytical methods in the study of variations in wild populations. As with the physical and chemical sciences, genetics has been enabled to make use of mathematics to compound (often theoretically out of simple units, the genes, the complexity known as an organism, much in the same way as a chemist compounds molecules with atoms and the physicist compounds atoms with protons and electrons. The determination of the scientific basis of heredity within the last two decades and the verification of the principal conclusions in many different plants and animals has made possible the application of analytical methods in the study of variations in wild populations. As with the physical and chemical sciences, genetics has been enabled to make use of mathematics to compound (often theoretically out of simple units, the genes, the complexity known as an organism, much in the same way as a chemist compounds molecules with atoms and the physicist compounds atoms with protons and electrons.
In PCoA, majority individuals of Metekel (L) tended to form separate group. The result of the study confirmed the presence of genetic diversity that can be exploited to improve the productivity. This calls for a conserted efforts in the collection, conservation and sustainable use of P. vulgaris. Keywords: Genetic diversity, ISSR, ...
Jakobsen, L P; Pfeiffer, P; Andersen, M
Congenital anterior midline cervical cleft (CAMCC) is a rare anomaly, with less than 100 cases reported. The cause of CAMCC is unknown, but genetic factors must be considered as part of the etiology. Three cases of CAMCC are presented. This is the first genetic study of isolated CAMCC. Conventional...
Common wheat ( Triticum aestivum L.) is a grass species, cultivated world wide. Globally, it is the most important human food grain and ranks second in total production as a cereal crop behind maize. Genetic diversity evaluation of germplasm is the basis of improvement in wheat. In the present study genetic diversity of 10 ...
Molecular evaluation of genetic diversity and association studies in rice. (Oryza sativa L.) C. Vanniarajan, K. K. Vinod and Andy Pereira. J. Genet. 91, 9–19. Table 1. Chromosome-wise distribution of SSR alleles and their number (k), polymorphic information content (PIC) and allele discrimination index (Dm). Chromosome.
Peeters, B.; Benninga, M. A.; Hennekam, R. C.
Constipation is a common problem in children but little is known about its exact pathophysiology. Environmental, behavioural but also genetic factors are thought to play a role in the aetiology of childhood constipation. We provide an overview of genetic studies performed in constipation. Until now,
Dec 17, 2008 ... Study of genetic diversity in Sudanese sesame. (Sesamum indicum L.) germplasm using random amplified polymorphic DNA (RAPD) markers. E. Abdellatef 1*, R. Sirelkhatem 1, M. M. Mohamed Ahmed1, K. H. Radwan2 and. M. M. Khalafalla1. 1Commission for Biotechnology and Genetic Engineering, ...
Zimmerman, Rebekah S; Jalas, Chaim; Tao, Xin; Fedick, Anastasia M; Kim, Julia G; Pepe, Russell J; Northrop, Lesley E; Scott, Richard T; Treff, Nathan R
To develop a novel and robust protocol for multifactorial preimplantation genetic testing of trophectoderm biopsies using quantitative polymerase chain reaction (qPCR). Prospective and blinded. Not applicable. Couples indicated for preimplantation genetic diagnosis (PGD). None. Allele dropout (ADO) and failed amplification rate, genotyping consistency, chromosome screening success rate, and clinical outcomes of qPCR-based screening. The ADO frequency on a single cell from a fibroblast cell line was 1.64% (18/1,096). When two or more cells were tested, the ADO frequency dropped to 0.02% (1/4,426). The rate of amplification failure was 1.38% (55/4,000) overall, with 2.5% (20/800) for single cells and 1.09% (35/3,200) for samples that had two or more cells. Among 152 embryos tested in 17 cases by qPCR-based PGD and CCS, 100% were successfully given a diagnosis, with 0% ADO or amplification failure. Genotyping consistency with reference laboratory results was >99%. Another 304 embryos from 43 cases were included in the clinical application of qPCR-based PGD and CCS, for which 99.7% (303/304) of the embryos were given a definitive diagnosis, with only 0.3% (1/304) having an inconclusive result owing to recombination. In patients receiving a transfer with follow-up, the pregnancy rate was 82% (27/33). This study demonstrates that the use of qPCR for PGD testing delivers consistent and more reliable results than existing methods and that single gene disorder PGD can be run concurrently with CCS without the need for additional embryo biopsy or whole genome amplification. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Lee, Han-Kyeong; Kim, Ji-Hae; Fava, Maurizio; Mischoulon, David; Park, Jae-Hyun; Shim, Eun-Jung; Lee, Eun-Ho; Lee, Ji Hyeon; Jeon, Hong Jin
The aim of this study was to develop a screening questionnaire that could distinguish individuals at high risk of smartphone overuse from casual users. The reliability, validity, and diagnostic ability of the Smartphone Overuse Screening Questionnaire (SOS-Q) were evaluated. Preliminary items were assessed by 50 addiction experts on-line, and 28 questions were selected. A total of 158 subjects recruited from six community centers for internet addiction participated in this study. The SOS-Q, Young's internet addiction scale, Korean scale for internet addiction, and Smartphone Scale for Smartphone Addiction (S-Scale) were used to assess the concurrent validity. Construct validity was supported by a six-factor model using an exploratory factor analysis. The internal consistency and the item-total correlations were favorable (α = 0.95, r = 0.35-0.81). The test-retest reliability was moderate (r = 0.70). The SOS-Q showed superior concurrent validity with the highest correlation between the S-Scale (r = 0.76). Receiver operating characteristic curve analysis revealed an area under the curve of 0.877. A cut-off point of 49 effectively categorized addiction high-risk group with a sensitivity of 0.81 and specificity of 0.86. Overall, the current study supports the use of SOS-Q as both a primary and supplementary measurement tool in a variety of settings. Copyright © 2017 Elsevier B.V. All rights reserved.
Genetic diversity, classification and comparative study on the larval phenotypic ... B. mori showed different performance based on larval phenotypic data. The analysis of variance regarding the studied traits showed that different strains have ...
Andreassen, Trude; Weiderpass, Elisabete; Nicula, Florian; Suteu, Ofelia; Itu, Andreea; Bumbu, Minodora; Tincu, Aida; Ursin, Giske; Moen, Kåre
Romania has Europe's highest incidence and mortality of cervical cancer. While a free national cervical cancer-screening programme has been in operation since 2012, participation in the programme is low, particularly in minority populations. The aim of this study was to explore Roma women's (non)participation in the programme from women's own perspectives and those of healthcare providers and policy makers. We carried out fieldwork for a period of 125 days in 2015/16 involving 144 study participants in Cluj and Bucharest counties. Fieldwork entailed participant observation, qualitative interviewing and focus group discussions. A striking finding was that screening providers and Roma women had highly different takes on the national screening programme. We identified four fundamental questions about which there was considerable disagreement between them: whether a free national screening programme existed in the first place, whether Roma women were meant to be included in the programme if it did, whether Roma women wanted to take part in screening, and to what degree screening participation would really benefit women's health. On the background of insights from actor-network theory, the article discusses to what degree the programme could be said to speak to the interest of its intended Roma public, and considers the controversies in light of the literature on patient centred care and user involvement in health care. The paper contributes to the understanding of the health and health-related circumstances of the largest minority in Europe. It also problematizes the use of the concept of "barriers" in research into participation in cancer screening, and exemplifies how user involvement can potentially help transform and improve screening programmes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Hasselbalch, Ann Louise
residual genetic influence existed. Based on information about habitual diet from the FFQ the genetic influence on total energy intake, macronutrient intake, as well as intake of energy from 20 food groups, was estimated. The proportion of variation in dietary intake explained by variation in genes...... exposures as well as genetic differences between individuals, resulting in differentiated susceptibility to environmental exposures. The evidence for genetic influence on anthropometry has previously been established and has been estimated to be 60-70% based on twin studies. These inter...... mass, but only limited evidence for associations between habitual dietary intake and anthropometry exists. Differences in habitual dietary intake are also partly determined by differences in genes influencing smell and taste preferences. But, so far, only few studies have investigated genetic...
Dietrich, Andrea; Fernandez, Thomas V; King, Robert A
Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarif......Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet......, it is clear that large patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene...... discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent-child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA...
Cheong, Kyu Hoi; Cheong, Hae Won; Cheon, Kwi Cheong; Kim, Chae Sung
To investigate genetic damage of radiation in mammalian male germ cell, sperm head counts, frequency of sperm with abnormal head shape, fertility, activity of LDH-X, and the induction of unscheduled DNA synthesis in testis were measured periodically after irradiation. Sperm head counts and activities of LDH-X in testes were gradually reduced by increased radiation dose and with the passing of the time after irradiation. Frequency occurrence of sperm of abnormal head shape, sterile period, and the induction of unscheduled DNA synthesis were increased. (Author)
Haploid are plants with a gametophytic chromosome number and doubled haploid are dihaploids that have undergone chromosome duplication. The production of haploid and doubled haploid (DHs) through gametic embryogenesis allows a single-step development of complete homozygous lines from heterozygous parents, shortening the time required to produce homozygous plants in comparison with the conventional breeding methods that employ several generations of selfing. The production of haploid and DHs provides a particularly attractive biotechnological tool, and the development of haploidy technology and protocols to produce homozygous plants has had a significant impact on agricultural systems. Nowadays, these bio technologies represent an integral part of the breeding programmes of many agronomically important crops. There are several available methods to obtain haploid and DHs, of which in vitro anther or isolated microspore culture are the most effective and widely used (Germana Maria 2011). Tissue culture techniques, particularly short-term culture procedures such as shoot-tip culture and regeneration from primary explants, have been proposed as methods for obtaining large numbers of plants identical to the plant used as an explant source( Evans et al., 1984). Nicotiana spp. are one of the most important commercial crops in the world ( Liu and Zhang, 2008). Nicotiana alata is member from family solanacea, it is ornamental plant and the diploid cells contains 18 chromosomes. Nitsch (1969) reported the first production of haploid plants through anther culture and regeneration of plants of Nicotiana alata, For these reasons they have been considered to suitable candidates for model species in somatic cell genetics research( Bourgin et al., 1979). Radiobiological studies on plant tissues in culture may provide information on the cell growth behavior, radiosensitivity and the induction of mutations. The radiosensitivity of plants and calli can be manifested mostly in three
Full Text Available Abstract Background The advent of urine testing for Chlamydia trachomatis has raised the possibility of large-scale screening for this sexually transmitted infection, which is now the most common in the United Kingdom. The purpose of this study was to investigate the effect of an invitation to be screened for chlamydia and of receiving a negative result on levels of anxiety, depression and self-esteem. Methods 19,773 men and women aged 16 to 39 years, selected at random from 27 general practices in two large city areas (Bristol and Birmingham were invited by post to send home-collected urine samples or vulvo-vaginal swabs for chlamydia testing. Questionnaires enquiring about anxiety, depression and self-esteem were sent to random samples of those offered screening: one month before the dispatch of invitations; when participants returned samples; and after receiving a negative result. Results Home screening was associated with an overall reduction in anxiety scores. An invitation to participate did not increase anxiety levels. Anxiety scores in men were lower after receiving the invitation than at baseline. Amongst women anxiety was reduced after receipt of negative test results. Neither depression nor self-esteem scores were affected by screening. Conclusion Postal screening for chlamydia does not appear to have a negative impact on overall psychological well-being and can lead to a decrease in anxiety levels among respondents. There is, however, a clear difference between men and women in when this reduction occurs.
Campbell, Rona; Mills, Nicola; Sanford, Emma; Graham, Anna; Low, Nicola; Peters, Tim J
The advent of urine testing for Chlamydia trachomatis has raised the possibility of large-scale screening for this sexually transmitted infection, which is now the most common in the United Kingdom. The purpose of this study was to investigate the effect of an invitation to be screened for chlamydia and of receiving a negative result on levels of anxiety, depression and self-esteem. 19,773 men and women aged 16 to 39 years, selected at random from 27 general practices in two large city areas (Bristol and Birmingham) were invited by post to send home-collected urine samples or vulvo-vaginal swabs for chlamydia testing. Questionnaires enquiring about anxiety, depression and self-esteem were sent to random samples of those offered screening: one month before the dispatch of invitations; when participants returned samples; and after receiving a negative result. Home screening was associated with an overall reduction in anxiety scores. An invitation to participate did not increase anxiety levels. Anxiety scores in men were lower after receiving the invitation than at baseline. Amongst women anxiety was reduced after receipt of negative test results. Neither depression nor self-esteem scores were affected by screening. Postal screening for chlamydia does not appear to have a negative impact on overall psychological well-being and can lead to a decrease in anxiety levels among respondents. There is, however, a clear difference between men and women in when this reduction occurs.
Bhawna Bhutoria Jain; Rabindra Nath Roy; Sulekha Ghosh; Tapan Ghosh; Uma Banerjee; Subodh Kumar Bhattacharya
Hemoglobinopathies are common genetic disorders of hemoglobin, which can be prevented by population screening and offering genetic counseling. In absence of population-based screening for hemoglobinopathies, the hospital-based diagnosis register provide idea about the extent of problem in the community. The present study was undertaken to find out the burden of hemoglobinopathies and spectrum of this disorders among the population who were screened in the hospital-based screening program. A r...
Bihrmann, Kristine; Jensen, Allan; Olsen, Anne Helene
screening were calculated. RESULTS: Defining BI-RADS(trade mark) 4-5 as a positive screening outcome, the overall sensitivity of opportunistic screening was 33.6% and the specificity was 99.1%. Using BI-RADS(trade mark) 3-5 as positive, the sensitivity was 37.4% and the specificity was 97.9%. Organized...... screening (which was not categorized according to BI-RADS(trade mark)) had an overall sensitivity of 67.2% and a specificity of 98.4%. CONCLUSION: Our study showed a considerably higher sensitivity in organized screening than in opportunistic screening, while the specificity was fairly similar in the two...
Laux, John M.; Piazza, Nick J.; Salyers, Kathleen; Roseman, Christopher P.
The sensitivity of the Substance Abuse Subtle Screening Inventory-3 (SASSI-3) was examined among substance-dependent adults enrolled in a family drug court. The SASSI-3 had a high sensitivity rate with this population, even across varying levels of motivation to change. (Contains 2 tables.)
Huber, Ingrid; Block, Annette; Sebah, Daniela; Debode, Frédéric; Morisset, Dany; Grohmann, Lutz; Berben, Gilbert; Stebih, Dejan; Milavec, Mojca; Zel, Jana; Busch, Ulrich
Worldwide, qualitative methods based on PCR are most commonly used as screening tools for genetically modified material in food and feed. However, the increasing number and diversity of genetically modified organisms (GMO) require effective methods for simultaneously detecting several genetic elements marking the presence of transgenic events. Herein we describe the development and validation of a pentaplex, as well as complementary triplex and duplex real-time PCR assays, for the detection of the most common screening elements found in commercialized GMOs: P-35S, T-nos, ctp2-cp4-epsps, bar, and pat. The use of these screening assays allows the coverage of many GMO events globally approved for commercialization. Each multiplex real-time PCR assay shows high specificity and sensitivity with an absolute limit of detection below 20 copies for the targeted sequences. We demonstrate by intra- and interlaboratory tests that the assays are robust as well as cost- and time-effective for GMO screening if applied in routine GMO analysis.
Apr 25, 2014 ... future studies from the authors. The remaining leaves ... βij the random contribution for the jth individual of the ith biogeographic province ... quantifying genetic structure accounting for the complexities of spatial correlation in ...
First page Back Continue Last page Overview Graphics. Molecular Genetic Studies of Some Eye Diseases Affecting the Indian Population. Single gene disorders. Complex eye diseases. Genotype-phenotype correlation. Molecular diagnostics.
Buxbaum Joseph D
Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.
Bergdahl, Anna Grenabo; Wilderäng, Ulrica; Aus, Gunnar; Carlsson, Sigrid; Damber, Jan-Erik; Frånlund, Maria; Geterud, Kjell; Khatami, Ali; Socratous, Andreas; Stranne, Johan; Hellström, Mikael; Hugosson, Jonas
Background Magnetic resonance imaging (MRI) and targeted biopsies (TB) have shown potential to more accurately detect significant prostate cancer (PC) compared to prostate-specific antigen (PSA) and systematic biopsies (SB). Objective To compare sequential screening (PSA + MRI) with conventional PSA screening. Design, Setting and Participants Of 384 attendees in the 10th screening round of the Göteborg randomised screening trial, 124 men, median age 69.5, had a PSA of ≥1.8 ng/ml and underwent a prebiopsy MRI. Men with suspicious lesions on MRI and/or PSA ≥3.0 ng/ml were referred for biopsy. SB was performed blinded to MRI results and TB was performed in men with tumour-suspicious findings on MRI. Three screening strategies were compared (PSA≥3.0+SB; PSA≥3.0+MRI+TB and PSA≥1.8+MRI+TB). Outcome Measurements and Statistical Analysis Cancer detection rates, sensitivity and specificity were calculated per screening strategy and compared using McNemar´s test. Results and Limitations In total, 28 PC were detected, of which 20 were diagnosed in biopsy-naïve men. Both PSA≥3.0+MRI and PSA≥1.8+MRI significantly increased specificity compared with PSA≥3.0+SB (0.92 and 0.79 vs. 0.52; p=3.0+MRI (0.73 vs. 0.46, p=0.008). The detection rate of significant cancer was higher with PSA≥1.8+MRI compared to PSA≥3.0+SB (5.9 vs. 4.0%), while the detection rate of insignificant cancer was lowered by PSA≥3.0+MRI (0.3 vs. 1.2%). The primary limitation of this study is the small sample of men. Conclusion A screening strategy with a lowered PSA cut-off followed by TB in MRI-positive men seems to increase the detection of significant cancers while improving specificity. If replicated, these results may contribute to a paradigm shift in future screening. Patient Summary Major concerns in prostate-specific antigen screening are overdiagnosis and underdiagnosis. We evaluated whether prostate magnetic resonance imaging could improve the balance of benefits to harm in
Mitra, Anita V; Bancroft, Elizabeth K; Barbachano, Yolanda
mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA >3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (± 5 years) who were negative for the familial mutation. RESULTS: In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2......Study Type - Diagnostic (validating cohort) Level of Evidence 1b OBJECTIVES: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening...... in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported. MATERIALS AND METHODS: Men aged 40-69 years from families with BRCA1 or BRCA2...
Down's Syndrome prenatal diagnostic and screening techniques have spread widely in France over the last 30 years and are now part of the routine clinical practice of prenatal care. These techniques, which originated in the field of genetics, ultrasonography and biochemistry, were the first to provide the possibility of choosing the features of the foetus, or at least to reject some of its characteristics. They lead to new norms of healthy foetuses and a progressive acceptance of medical abortions. The aim of this paper is to understand how the use of these tests has been generalised in France despite scientific controversies about their risks and ethical questioning about a potential renewal of eugenics. It analyses the representations of public needs that have been articulated by key players in the scientific and medical fields. This research explores political and administrative decision making processes to understand how progressively widening public access to prenatal testing has been organised and funded. The results highlight the scientific and political role of biomedical researchers, the forms of involvement of health authorities and politicians, and the passive participation of the vast majority of the users. The paper also examines the characteristics of the French health system that facilitated the generalised use of the technology.
Gason, Alexandra A; Aitken, MaryAnne; Delatycki, Martin B; Sheffield, Edith; Metcalfe, Sylvia A
Tay Sachs disease is a recessively inherited neurodegenerative disorder, for which carrier screening programs exist worldwide. Education for those offered a screening test is essential in facilitating informed decision-making. In Melbourne, Australia, we have designed, developed, and evaluated a computer-based instructional resource for use in the Tay Sachs disease carrier screening program for secondary school students attending Jewish schools. The resource entitled "Genetics in the Community: Tay Sachs disease" was designed on a platform of educational learning theory. The development of the resource included formative evaluation using qualitative data analysis supported by descriptive quantitative data. The final resource was evaluated within the screening program and compared with the standard oral presentation using a questionnaire. Knowledge outcomes were measured both before and after either of the educational formats. Data from the formative evaluation were used to refine the content and functionality of the final resource. The questionnaire evaluation of 302 students over two years showed the multimedia resource to be equally effective as an oral educational presentation in facilitating participants' knowledge construction. The resource offers a large number of potential benefits, which are not limited to the Tay Sachs disease carrier screening program setting, such as delivery of a consistent educational message, short delivery time, and minimum financial and resource commitment. This article outlines the value of considering educational theory and describes the process of multimedia development providing a framework that may be of value when designing genetics multimedia resources in general.
Turmel, Julie; Poirier, Paul; Bougault, Valérie; Blouin, Evelyne; Belzile, Mireille; Boulet, Louis-Philippe
Cardiorespiratory disorders are common in athletes. However, these conditions are often underdiagnosed, which potentially results in impaired performance and increased health risks. The aim of this study was to evaluate, in a research setting, the prevalence of cardiorespiratory disorders in athletes in order to determine the potential value of a screening program. One hundred thirty-three athletes were studied. Each subject underwent a physical examination. A eucapnic voluntary hyperventilation (EVH) test and a methacholine inhalation test were performed to confirm the diagnosis of asthma. A cardiovascular evaluation was also performed, including maximal exercise test with electrocardiogram, 24-hour ambulatory blood pressure monitoring, 24-hour Holter monitoring, and blood sampling. Seventy-four (56%) athletes had airway hyperresponsiveness to EVH or the methacholine inhalation test. Among those with airway hyperresponsiveness, 45 (61%) athletes were only hyperresponsive to EVH, and 10 (14%) were only hyperresponsive to the methacholine inhalation test (using the criteria of a PC20 ≤ 4 mg/mL). Thirty-two (24%) athletes had a known diagnosis of asthma, while 34 (26%) athletes received a new asthma diagnosis. Ninety-seven (73%) athletes were sensitized to common airborne allergens. Forty-seven (35%) athletes completed the cardiovascular evaluation. Three (6%) and 7 (15%) athletes had a previous or new diagnosis of cardiovascular disease, respectively. Resting systemic hypertension was documented in 2 (4%) athletes and exaggerated blood pressure response to exercise was found in 12 (26%) athletes. This cardiorespiratory screening data set in athletes showed a high prevalence of exercise-induced asthma and exercise hypertension, which in many cases were not previously diagnosed.
The principle and operational procedure of Integrated Circuits (ICs) screening with irradiation-and-anneal and multicomponent regression analysis are discussed. The key technology, advantages and shortcomings of the two methods are described in contrast, and some advices are given with the state-of-the-art of the screening technology
The phytotoxicity of the seed and phytochemical screening of the leaf of Ricinus communis were investigated. The secondary metabolites in the leaf were screened and identified. The leaves were sun dried, pulverized and sieved. The resulting powdered extract was subjected to phytochemical tests. A proximate analysis ...
Shimizu, Eri; Kato, Hisashi; Nakagawa, Yuki; Kodama, Takashi; Futo, Satoshi; Minegishi, Yasutaka; Watanabe, Takahiro; Akiyama, Hiroshi; Teshima, Reiko; Furui, Satoshi; Hino, Akihiro; Kitta, Kazumi
A novel type of quantitative competitive polymerase chain reaction (QC-PCR) system for the detection and quantification of the Roundup Ready soybean (RRS) was developed. This system was designed based on the advantage of a fully validated real-time PCR method used for the quantification of RRS in Japan. A plasmid was constructed as a competitor plasmid for the detection and quantification of genetically modified soy, RRS. The plasmid contained the construct-specific sequence of RRS and the taxon-specific sequence of lectin1 (Le1), and both had 21 bp oligonucleotide insertion in the sequences. The plasmid DNA was used as a reference molecule instead of ground seeds, which enabled us to precisely and stably adjust the copy number of targets. The present study demonstrated that the novel plasmid-based QC-PCR method could be a simple and feasible alternative to the real-time PCR method used for the quantification of genetically modified organism contents.
Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert
Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.
Oyler-McCance, S.J.; Ransler, F.A.; Berkman, L.K.; Quinn, T.W.
For management purposes, the range of naturally occurring trumpeter swans (Cygnus buccinator) has been divided into two populations, the Pacific Coast Population (PP) and the Rocky Mountain Population (RMP). Little is known about the distribution of genetic variation across the species' range despite increasing pressure to make difficult management decisions regarding the two populations and flocks within them. To address this issue, we used rapidly evolving genetic markers (mitochondrial DNA sequence and 17 nuclear microsatellite loci) to elucidate the underlying genetic structure of the species. Data from both markers revealed a significant difference between the PP and RMP with the Yukon Territory as a likely area of overlap. Additionally, we found that the two populations have somewhat similar levels of genetic diversity (PP is slightly higher) suggesting that the PP underwent a population bottleneck similar to a well-documented one in the RMP. Both genetic structure and diversity results reveal that the Tri-State flock, a suspected unique, non-migratory flock, is not genetically different from the Canadian flock of the RMP and need not be treated as a unique population from a genetic standpoint. Finally, trumpeter swans appear to have much lower mitochondrial DNA variability than other waterfowl studied thus far which may suggest a previous, species-wide bottleneck. ?? 2007 Springer Science+Business Media, Inc.
Niu, Chenqi; Xu, Yuancong; Zhang, Chao; Zhu, Pengyu; Huang, Kunlun; Luo, Yunbo; Xu, Wentao
As genetically modified (GM) technology develops and genetically modified organisms (GMOs) become more available, GMOs face increasing regulations and pressure to adhere to strict labeling guidelines. A singleplex detection method cannot perform the high-throughput analysis necessary for optimal GMO detection. Combining the advantages of multiplex detection and droplet digital polymerase chain reaction (ddPCR), a single universal primer-multiplex-ddPCR (SUP-M-ddPCR) strategy was proposed for accurate broad-spectrum screening and quantification. The SUP increases efficiency of the primers in PCR and plays an important role in establishing a high-throughput, multiplex detection method. Emerging ddPCR technology has been used for accurate quantification of nucleic acid molecules without a standard curve. Using maize as a reference point, four heterologous sequences ( 35S, NOS, NPTII, and PAT) were selected to evaluate the feasibility and applicability of this strategy. Surprisingly, these four genes cover more than 93% of the transgenic maize lines and serve as preliminary screening sequences. All screening probes were labeled with FAM fluorescence, which allows the signals from the samples with GMO content and those without to be easily differentiated. This fiveplex screening method is a new development in GMO screening. Utilizing an optimal amplification assay, the specificity, limit of detection (LOD), and limit of quantitation (LOQ) were validated. The LOD and LOQ of this GMO screening method were 0.1% and 0.01%, respectively, with a relative standard deviation (RSD) < 25%. This method could serve as an important tool for the detection of GM maize from different processed, commercially available products. Further, this screening method could be applied to other fields that require reliable and sensitive detection of DNA targets.
Garcia, Christine Kim
Genetic investigations of fibrotic diseases, including those of late onset, often yield unanticipated insights into disease pathogenesis. This Review focuses on pathways underlying lung fibrosis that are generalizable to other organs. Herein, we discuss genetic variants subdivided into those that shorten telomeres, activate the DNA damage response, change resident protein expression or function, or affect organelle activity. Genetic studies provide a window into the downstream cascade of maladaptive responses and pathways that lead to tissue fibrosis. In addition, these studies reveal interactions between genetic variants, environmental factors, and age that influence the phenotypic spectrum of disease. The discovery of forces counterbalancing inherited risk alleles identifies potential therapeutic targets, thus providing hope for future prevention or reversal of fibrosis.
Hartono, A. D.; Hakiki, Farizal; Syihab, Z.; Ambia, F.; Yasutra, A.; Sutopo, S.; Efendi, M.; Sitompul, V.; Primasari, I.; Apriandi, R.
EOR preliminary analysis is pivotal to be performed at early stage of assessment in order to elucidate EOR feasibility. This study proposes an in-depth analysis toolkit for EOR preliminary evaluation. The toolkit incorporates EOR screening, predictive, economic, risk analysis and optimisation modules. The screening module introduces algorithms which assimilates statistical and engineering notions into consideration. The United States Department of Energy (U.S. DOE) predictive models were implemented in the predictive module. The economic module is available to assess project attractiveness, while Monte Carlo Simulation is applied to quantify risk and uncertainty of the evaluated project. Optimization scenario of EOR practice can be evaluated using the optimisation module, in which stochastic methods of Genetic Algorithms (GA), Particle Swarm Optimization (PSO) and Evolutionary Strategy (ES) were applied in the algorithms. The modules were combined into an integrated package of EOR preliminary assessment. Finally, we utilised the toolkit to evaluate several Indonesian oil fields for EOR evaluation (past projects) and feasibility (future projects). The attempt was able to update the previous consideration regarding EOR attractiveness and open new opportunity for EOR implementation in Indonesia.
Hartono, A. D.
EOR preliminary analysis is pivotal to be performed at early stage of assessment in order to elucidate EOR feasibility. This study proposes an in-depth analysis toolkit for EOR preliminary evaluation. The toolkit incorporates EOR screening, predictive, economic, risk analysis and optimisation modules. The screening module introduces algorithms which assimilates statistical and engineering notions into consideration. The United States Department of Energy (U.S. DOE) predictive models were implemented in the predictive module. The economic module is available to assess project attractiveness, while Monte Carlo Simulation is applied to quantify risk and uncertainty of the evaluated project. Optimization scenario of EOR practice can be evaluated using the optimisation module, in which stochastic methods of Genetic Algorithms (GA), Particle Swarm Optimization (PSO) and Evolutionary Strategy (ES) were applied in the algorithms. The modules were combined into an integrated package of EOR preliminary assessment. Finally, we utilised the toolkit to evaluate several Indonesian oil fields for EOR evaluation (past projects) and feasibility (future projects). The attempt was able to update the previous consideration regarding EOR attractiveness and open new opportunity for EOR implementation in Indonesia.
Teng, Flora F; Mitchell, Sheona M; Sekikubo, Musa; Biryabarema, Christine; Byamugisha, Josaphat K; Steinberg, Malcolm; Money, Deborah M; Ogilvie, Gina S
To define embarrassment and develop an understanding of the role of embarrassment in relation to cervical cancer screening and self-collected human papillomavirus (HPV) DNA testing in Uganda. Cross-sectional, qualitative study using semistructured one-to-one interviews and focus groups. 6 key-informant health workers and 16 local women, purposively sampled. Key informant inclusion criteria: Ugandan members of the project team. Focus group inclusion criteria: woman age 30-69 years, Luganda or Swahili speaking, living or working in the target Ugandan community. unwillingness to sign informed consent. Primary and tertiary low-resource setting in Kampala, Uganda. In Luganda, embarrassment relating to cervical cancer is described in two forms. 'Community embarrassment' describes discomfort based on how a person may be perceived by others. 'Personal embarrassment' relates to shyness or discomfort with her own genitalia. Community embarrassment was described in themes relating to place of study recruitment, amount of privacy in dwellings, personal relationship with health workers, handling of the vaginal swab and misunderstanding of HPV self-collection as HIV testing. Themes of personal embarrassment related to lack of knowledge, age and novelty of the self-collection swab. Overall, embarrassment was a barrier to screening at the outset and diminished over time through education and knowledge. Fatalism regarding cervical cancer diagnosis, worry about results and stigma associated with a cervical cancer diagnosis were other psychosocial barriers described. Overcoming psychosocial barriers to screening can include peer-to-peer education, drama and media campaigns. Embarrassment and other psychosocial barriers may play a large role at the onset of a screening programme, but over time as education and knowledge increase, and the social norms around screening evolve, its role diminishes. The role of peer-to-peer education and community authorities on healthcare cannot be
Full Text Available Abstract Background In genetic association study of quantitative traits using F∞ models, how to code the marker genotypes and interpret the model parameters appropriately is important for constructing hypothesis tests and making statistical inferences. Currently, the coding of marker genotypes in building F∞ models has mainly focused on the biallelic case. A thorough work on the coding of marker genotypes and interpretation of model parameters for F∞ models is needed especially for genetic markers with multiple alleles. Results In this study, we will formulate F∞ genetic models under various regression model frameworks and introduce three genotype coding schemes for genetic markers with multiple alleles. Starting from an allele-based modeling strategy, we first describe a regression framework to model the expected genotypic values at given markers. Then, as extension from the biallelic case, we introduce three coding schemes for constructing fully parameterized one-locus F∞ models and discuss the relationships between the model parameters and the expected genotypic values. Next, under a simplified modeling framework for the expected genotypic values, we consider several reduced one-locus F∞ models from the three coding schemes on the estimability and interpretation of their model parameters. Finally, we explore some extensions of the one-locus F∞ models to two loci. Several fully parameterized as well as reduced two-locus F∞ models are addressed. Conclusions The genotype coding schemes provide different ways to construct F∞ models for association testing of multi-allele genetic markers with quantitative traits. Which coding scheme should be applied depends on how convenient it can provide the statistical inferences on the parameters of our research interests. Based on these F∞ models, the standard regression model fitting tools can be used to estimate and test for various genetic effects through statistical contrasts with the
Freire-Maia, A [Faculdade de Ciencias Medicas e Biologicas de Botucatu (Brazil). Departamento de Genetica
The load of mutations disclosed by inbreeding, according to the ethnic group of the parents, has been analyzed in our data. Besides the total of the population, a sample with no alien ancestrals has also been analyzed. Genetic load has been studied for absortions, still births, pos-natal mortality, total mortality, anomalies, total mortality + anomalies, and abnormalities in general.
The load of mutations disclosed by inbreeding, according to the ethnic group of the parents, has been analyzed in our data. Besides the total of the population, a sample with no alien ancestrals has also been analyzed. Genetic load has been studied for absortions, still births, pos-natal mortality, total mortality, anomalies, total mortality + anomalies, and abnormalities in general [pt
Full Text Available RNA interference (RNAi is a technique widely used for gene silencing in organisms and cultured cells, and depends on sequence homology between double-stranded RNA (dsRNA and target mRNA molecules. Numerous cell-based genome-wide screens have successfully identified novel genes involved in various biological processes, including signal transduction, cell viability/death, and cell morphology. However, cell-based screens cannot address cellular processes such as development, behavior, and immunity. Drosophila and Caenorhabditis elegans are two model organisms whose whole bodies and individual body parts have been subjected to RNAi-based genome-wide screening. Moreover, Drosophila RNAi allows the manipulation of gene function in a spatiotemporal manner when it is implemented using the Gal4/UAS system. Using this inducible RNAi technique, various large-scale screens have been performed in Drosophila, demonstrating that the method is straightforward and valuable. However, accumulated results reveal that the results of RNAi-based screens have relatively high levels of error, such as false positives and negatives. Here, we review in vivo RNAi screens in Drosophila and the methods that could be used to remove ambiguity from screening results.
Selmer, K K; Egeland, T; Solaas, M H
Background - Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. Objective - To study the occurrence of mutations in these genes in families...... with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. Material and methods - We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. Results - We...... identified only one mutation in SCN1A, which seems to be a rare variant with no functional consequence. Conclusion - This suggests that mutations in these three genes are not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia....
Thamsborg, Lise Holst; Andersen, Berit; Larsen, Lise Grupe
arm) or present screening plus an HPV test (HPV arm). The study started 1 February 2017 and will run over three screening rounds corresponding to 7-8 years. ANALYSES: The primary endpoint is cervical intraepithelial neoplasia grade 3 or above. The trial is undertaken as a non-inferiority study......INTRODUCTION: The first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated women. These women are better protected against cervical cancer and could...... vaccination as girls. METHODS: Trial23 is a method study embedded in the existing cervical screening programme in four out of five Danish regions. Without affecting the screening programme, women born in 1994 are randomised to present screening with liquid-based cytology every third year (present programme...
Full Text Available Abstract Background Recent developments have made screening tests for foetal abnormalities available earlier in pregnancy and women have a range of testing options accessible to them. It is now recommended that all women, regardless of their age, are provided with information on prenatal screening tests. General Practitioners (GPs are often the first health professionals a woman consults in pregnancy. As such, GPs are well positioned to inform women of the increasing range of prenatal screening tests available. The aim of this study was to explore GPs experience of informing women of prenatal genetic screening tests for foetal abnormality. Methods A qualitative study consisting of four focus groups was conducted in metropolitan and rural Victoria, Australia. A discussion guide was used and the audio-taped transcripts were independently coded by two researchers using thematic analysis. Multiple coders and analysts and informant feedback were employed to reduce the potential for researcher bias and increase the validity of the findings. Results Six themes were identified and classified as 'intrinsic' if they occurred within the context of the consultation or 'extrinsic' if they consisted of elements that impacted on the GP beyond the scope of the consultation. The three intrinsic themes were the way GPs explained the limitations of screening, the extent to which GPs provided information selectively and the time pressures at play. The three extrinsic factors were GPs' attitudes and values towards screening, the conflict they experienced in offering screening information and the sense of powerlessness within the screening test process and the health care system generally. Extrinsic themes reveal GPs' attitudes and values to screening and to disability, as well as raising questions about the fundamental premise of testing. Conclusion The increasing availability and utilisation of screening tests, in particular first trimester tests, has expanded GPs
Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.
Nogueira, A M; Ferreira, M F S; Guilhen, J H S; Ferreira, A
The family Myrtaceae is widespread in the Atlantic Forest and is well-represented in the Espírito Santo State in Brazil. In the genus Psidium of this family, guava (Psidium guajava L.) is the most economically important species. Guava is widely cultivated in tropical and subtropical countries; however, the widespread cultivation of only a small number of guava tree cultivars may cause the genetic vulnerability of this crop, making the search for promising genotypes in natural populations important for breeding programs and conservation. In this study, the genetic diversity of 66 guava trees sampled in the southern region of Espírito Santo and in Caparaó, MG, Brazil were evaluated. A total of 28 morphological descriptors (11 quantitative and 17 multicategorical) and 18 microsatellite markers were used. Principal component, discriminant and cluster analyses, descriptive analyses, and genetic diversity analyses using simple sequence repeats were performed. Discrimination of accessions using molecular markers resulted in clustering of genotypes of the same origin, which was not observed using morphological data. Genetic diversity was detected between and within the localities evaluated, regardless of the methodology used. Genetic differentiation among the populations using morphological and molecular data indicated the importance of the study area for species conservation, genetic erosion estimation, and exploitation in breeding programs.
Bancroft, Elizabeth K.; Page, Elizabeth C.; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S.; Mitchell, Gillian; Drew, Kate; Mæhle, Lovise; Axcrona, Karol; Evans, D. Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A.; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J.; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A.; Oosterwijk, Jan C.; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J.; Buys, Saundra; Conner, Tom; Ausems, Margreet G.; Ong, Kai-Ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R.; Maia, Sofia; Foulkes, William D.; Taherian, Nassim; Ruijs, Marielle; van Os, Theo
Background: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in
Bancroft, Elizabeth K.; Page, Elizabeth C.; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S.; Mitchell, Gillian; Drew, Kate; Maehle, Lovise; Axcrona, Karol; Evans, D. Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A.; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J.; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A.; Oosterwijk, Jan C.; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J.; Buys, Saundra; Conner, Tom; Ausems, Margreet G.; Ong, Kai-ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R.; Maia, Sofia; Foulkes, William D.; Taherian, Nassim; Ruijs, Marielle; Helderman-van den Enden, Apollonia T.
Background: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in
Shamonki, Mousa I; Jin, Helen; Haimowitz, Zachary; Liu, Lian
To assess whether preimplantation genetic screening (PGS) is possible by testing for free embryonic DNA in spent IVF media from embryos undergoing trophectoderm biopsy. Prospective cohort analysis. Academic fertility center. Seven patients undergoing IVF and 57 embryos undergoing trophectoderm biopsy for PGS. On day 3 of development, each embryo was placed in a separate media droplet. All biopsied embryos received a PGS result by array comparative genomic hybridization. Preimplantation genetic screening was performed on amplified DNA extracted from media and results were compared with PGS results for the corresponding biopsy.  Presence of DNA in spent IVF culture media.  Correlation between genetic screening result from spent media and corresponding biopsy. Fifty-five samples had detectable DNA ranging from 2-642 ng/μL after a 2-hour amplification. Six samples with the highest DNA levels underwent PGS, rendering one result with a derivative log ratio SD (DLRSD) of media and a result that is consistent with trophectoderm biopsy. Improvements in DNA collection, amplification, and testing may allow for PGS without biopsy in the future. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Richard T Timms
Full Text Available The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral ubiquitin E3 ligases which downregulate MHC-I and additional cell surface immunoreceptors. To identify novel cellular genes required for K5 function we performed a forward genetic screen in near-haploid human KBM7 cells. The screen identified proteolipid protein 2 (PLP2, a MARVEL domain protein of unknown function, as essential for K5 activity. Genetic loss of PLP2 traps the viral ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5-expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range of novel K5 targets, all of which required PLP2 for their K5-mediated downregulation. This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system.
Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.
Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non
Shen, J D; Wu, W; Shu, L; Cai, L L; Xie, J Z; Ma, L; Sun, X P; Cui, Y G; Liu, J Y
Objective: To evaluate the efficiency of the application of array comparative genomic hybridization (array-CGH) in preimplantation genetic diagnosis or screening (PGD/PGS), and compare the clinical outcomes of different stage embryo biopsy. Methods: The outcomes of 381 PGD/PGS cycles referred in the First Affiliated Hospital of Nanjing Medical University from July 2011 to August 2015 were retrospectively analyzed. There were 320 PGD cycles with 156 cleavage-stage-biopsy cycles and 164 trophectoderm-biopsy cycles, 61 PGS cycles with 23 cleavage-stage-biopsy cycles and 38 trophectoderm-biopsy cycles. Chromosomal analysis was performed by array-CGH technology combined with whole genome amplification. Single embryo transfer was performed in all transfer cycles. Live birth rate was calculated as the main clinical outcomes. Results: The embryo diagnosis rate of PGD/PGS by array-CGH were 96.9%-99.1%. In PGD biopsy cycles, the live birth rate per embryo transfer cycle and live birth rate per embryo biopsy cycle were 50.0%(58/116) and 37.2%(58/156) in cleavage-stage-biopsy group, 67.5%(85/126) and 51.8%(85/164) in trophectoderm-biopsy group (both P 0.05). Conclusions: High diagnosis rate and idea live birth rate are achieved in PGD/PGS cycles based on array-CGH technology. The live birth rate of trophectoderm-biopsy group is significantly higher than that of cleavage-stage-biopsy group in PGD cycles; the efficiency of trophectoderm-biopsy is better.
Sana, Barindra; Chia, Kuan Hui Burton; Raghavan, Sarada S; Ramalingam, Balamurugan; Nagarajan, Niranjan; Seayad, Jayasree; Ghadessy, Farid J
Lignin is a potential biorefinery feedstock for the production of value-added chemicals including vanillin. A huge amount of lignin is produced as a by-product of the paper industry, while cellulosic components of plant biomass are utilized for the production of paper pulp. In spite of vast potential, lignin remains the least exploited component of plant biomass due to its extremely complex and heterogenous structure. Several enzymes have been reported to have lignin-degrading properties and could be potentially used in lignin biorefining if their catalytic properties could be improved by enzyme engineering. The much needed improvement of lignin-degrading enzymes by high-throughput selection techniques such as directed evolution is currently limited, as robust methods for detecting the conversion of lignin to desired small molecules are not available. We identified a vanillin-inducible promoter by RNAseq analysis of Escherichia coli cells treated with a sublethal dose of vanillin and developed a genetically programmed vanillin-sensing cell by placing the 'very green fluorescent protein' gene under the control of this promoter. Fluorescence of the biosensing cell is enhanced significantly when grown in the presence of vanillin and is readily visualized by fluorescence microscopy. The use of fluorescence-activated cell sorting analysis further enhances the sensitivity, enabling dose-dependent detection of as low as 200 µM vanillin. The biosensor is highly specific to vanillin and no major response is elicited by the presence of lignin, lignin model compound, DMSO, vanillin analogues or non-specific toxic chemicals. We developed an engineered E. coli cell that can detect vanillin at a concentration as low as 200 µM. The vanillin-sensing cell did not show cross-reactivity towards lignin or major lignin degradation products including vanillin analogues. This engineered E. coli cell could potentially be used as a host cell for screening lignin-degrading enzymes that
Bhagwan Mariba Waghmare
Full Text Available Objective: To study the antibacterial screening of corm of Amorphophallus campanulatus (Roxb. (A. campanulatus. Methods: Antibacterial activities of methanolic, petroleum ether and ethyl acetate extracts of corm of A. campanulatus were studied by agar diffusion technique to determine in vitro antibacterial activities. The antibacterial activity was measured with respect to the standard antibacterial drug. In addition, minimum inhibitory concentration was also determined by using serial dilution method to determine and evaluate antibacterial potency of test corm extracts of A. campanulatus. Results: The results showed significant antibacterial activities against four pathogenic bacteria. The minimum inhibitory concentration values against test bacteria were found to be remarkable range in bacteria like methicillin-resistant Staphylococcus aureus at concentration 0.25 mg/ well, in Pseudomonas aeruginosa at 0.5 mg/well concentration, in Vibrio cholerae was 2 mg/ well, Streptococcus pyogenes at concentration of 0.5 mg/well and Proteus mirabilis was at concentration of 2 mg/well. Conclusions: The methanolic and petroleum ether extracts are capable to maximum inhibition of the tested pathogenic bacteria.
Alfaro, Karla M; Gage, Julia C; Rosenbaum, Alan J; Ditzian, Lauren R; Maza, Mauricio; Scarinci, Isabel C; Miranda, Esmeralda; Villalta, Sofia; Felix, Juan C; Castle, Philip E; Cremer, Miriam L
Cervical cancer is the third most commonly occurring cancer among women and the fourth leading cause of cancer-related deaths in women worldwide, with more than 85 % of these cases occurring in developing countries. These global disparities reflect the differences in cervical cancer screening rates between high-income and medium- and low-income countries. At 19 %, El Salvador has the lowest reported screening coverage of all Latin American countries. The purpose of this study is to identify factors affecting public sector HPV DNA-based cervical cancer screening participation in El Salvador. This study was nested within a public sector screening program where health promoters used door-to-door outreach to recruit women aged 30-49 years to attend educational sessions about HPV screening. A subgroup of these participants was chosen randomly and questioned about demographic factors, healthcare utilization, previous cervical cancer screening, and HPV knowledge. Women then scheduled screening appointments at their public health clinics. Screening participants were adherent if they attended their scheduled appointment or rescheduled and were screened within 6 months. The association between non-adherence and demographic variables, medical history, history of cancer, sexual history, birth control methods, and screening barriers was assessed using Chi-square tests of significance and logistic regression. All women (n = 409) enrolled in the study scheduled HPV screening appointments, and 88 % attended. Non-adherence was associated with a higher number of lifetime partners and being under-screened-defined as not having participated in cervical cancer screening within the previous 3 years (p = 0.03 and p = 0.04, respectively); 22.8 % of participants in this study were under-screened. Adherence to cervical cancer screening after educational sessions was higher than expected, in part due to interactions with the community-based health promoters as well as the educational session
Seven, Memnun; Eroglu, Kafiye; Akyüz, Aygül; Ingvoldstad, Charlotta
The latest advances in genetics/genomics have significantly impacted prenatal screening and diagnostic tests. This cross-sectional descriptive study was conducted in inpatient and outpatient obstetric clinics in 24 hospitals in Turkey to determine knowledge of genetics related to prenatal care and the educational needs of perinatal nurses. A total of 116 nurses working in these clinics agreed to participate. The results included the level of knowledge among nurses was not affected by sociodemographic factors. Also, there is a lack of knowledge and interest in genetics among prenatal nurses and in clinical practice to provide education and counseling related to genetics in prenatal settings as a part of prenatal care. © 2017 John Wiley & Sons Australia, Ltd.
te Meerman, Sanne; Batstra, Laura; Hoekstra, Rink; Grietens, Hans
Academic study books are essential assets for disseminating knowledge about ADHD to future healthcare professionals. This study examined if they are balanced with regard to genetics. We selected and analyzed study books (N=43) used in (pre) master's programmes at 10 universities in the Netherlands.
Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells
... Inherited disorders include sickle cell disease , cystic fibrosis , Tay–Sachs disease , and many others. In most cases, both parents ... pain. It occurs most often in African Americans. Tay–Sachs Disease: An inherited birth defect that causes intellectual disability, ...
Murchison, Ann P; Friedman, David S; Gower, Emily W; Haller, Julia A; Lam, Byron L; Lee, David J; McGwin, Gerald; Owsley, Cynthia; Saaddine, Jinan; Insight Study Group
Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years within the United States. The Innovative Network for Sight Research group (INSIGHT) designed the Diabetic Eye Screening Study (DESS) to examine the feasibility and short-term effectiveness of non-mydriatic diabetic retinopathy (DR) screening for adults with diabetes in community-based settings. Study enrollment began in December 2011 at four sites: an internal medicine clinic at a county hospital in Birmingham, Alabama; a Federally-qualified community healthcare center in Miami-Dade County, Florida; a university-affiliated outpatient pharmacy in Philadelphia, Pennsylvania; and a medical home in Winston-Salem, North Carolina. People 18 years or older with previously diagnosed diabetes were offered free DR screening using non-mydriatic retinal photography that was preceded by a brief questionnaire addressing demographic information and previous eye care use. Visual acuity was also measured for each eye. Images were evaluated at a telemedicine reading center by trained evaluators using the National Health System DR grading classification. Participants and their physicians were sent screening report results and telephoned for a follow-up survey 3 months post-screening to determine whether participants had sought follow-up comprehensive eye care and their experiences with the screening process. Target enrollment at each site was a minimum of 500 persons. Three of the four sites met this enrollment goal. The INSIGHT/DESS is intended to establish the feasibility and short-term effectiveness of DR screening using non-mydriatic retinal photography in persons with diabetes who seek services in community-based clinic and pharmacy settings.
Oud, Manon S; Ramos, Liliana; O'Bryan, Moira K; McLachlan, Robert I; Okutman, Özlem; Viville, Stephane; de Vries, Petra F; Smeets, Dominique F C M; Lugtenberg, Dorien; Hehir-Kwa, Jayne Y; Gilissen, Christian; van de Vorst, Maartje; Vissers, Lisenka E L M; Hoischen, Alexander; Meijerink, Aukje M; Fleischer, Kathrin; Veltman, Joris A; Noordam, Michiel J
Microdeletions of the Y chromosome (YCMs), Klinefelter syndrome (47,XXY), and CFTR mutations are known genetic causes of severe male infertility, but the majority of cases remain idiopathic. Here, we describe a novel method using single molecule Molecular Inversion Probes (smMIPs), to screen infertile men for mutations and copy number variations affecting known disease genes. We designed a set of 4,525 smMIPs targeting the coding regions of causal (n = 6) and candidate (n = 101) male infertility genes. After extensive validation, we screened 1,112 idiopathic infertile men with non-obstructive azoospermia or severe oligozoospermia. In addition to five chromosome YCMs and six other sex chromosomal anomalies, we identified five patients with rare recessive mutations in CFTR as well as a patient with a rare heterozygous frameshift mutation in SYCP3 that may be of clinical relevance. This results in a genetic diagnosis in 11-17 patients (1%-1.5%), a yield that may increase significantly when more genes are confidently linked to male infertility. In conclusion, we developed a flexible and scalable method to reliably detect genetic causes of male infertility. The assay consolidates the detection of different types of genetic variation while increasing the diagnostic yield and detection precision at the same or lower price compared with currently used methods. © 2017 Wiley Periodicals, Inc.
Reynolds, Fiona; Stanistreet, Debbi; Elton, Peter
Abstract Background Several studies in the UK have suggested that women with learning disabilities may be less likely to receive cervical screening tests and a previous local study in had found that GPs considered screening unnecessary for women with learning disabilities. This study set out to ascertain whether women with learning disabilities are more likely to be ceased from a cervical screening programme than women without; and to examine the reasons given for ceasing women with learning ...
Abomohra, Abd El-Fatah; El-Naggar, Amal Hamed; Baeshen, Areej Ali
Nowadays, biofuel production is a fast expanding industry and is facing a growing dilemma about a feedstock source capable of keeping up with demand. Recently, macroalgae have been attracting a wide attention as a source for biofuel. In the present study, ten macroalgae were collected and screened as biodiesel feedstocks. As a result of their high biomass production and relatively high lipid content, Ulva lactuca, Padina boryana and Ulva intestinalis showed the highest significant lipids and fatty acid methyl esters (FAMEs) areal productivities among the studied species. Saturated fatty acids (SAFs) showed insignificant differences in the selected species, with noticeably significant higher polyunsaturated fatty acids (PUFAs) content in U. lactuca by 4.2 and 3 times, with respect to P. boryana and U. intestinalis, respectively. The recorded increase in PUFAs was attributed to higher content of C16:4n-3, C18:3n-3 and C18:4n-3. By lipid fractionation, P. boryana showed significant higher concentration of neutral lipids (37.7 mg g -1 CDW, representing 46.7% of total fatty acids) in comparison to U. lactuca and U. intestinalis, which showed 16% and 17% lower neutral lipid fractions, respectively. In addition, biodiesel characteristics of the studied macroalgae complied with that of international standards. Furthermore, oil-free residual biomass can be readily converted into fermentable sugars or biogas due to its high carbohydrates content, which adds to the economics of macroalgae as biofuel feedstock. In conclusion, the present study confirmed that macroalgae represent an attractive alternative renewable feedstock for biodiesel and other biofuels. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
El-Masry, H.G.; Foda, M.S.
In these studies 23 yeasts cultures belonging to 10 genera of ascosporogenous, ballistosporogenous, and asporogenous yeasts, were screened with respect to their abilities of hydrocarbon utilization in synthetic media. Thus, kerosene, n-hexadecane, and wax distillate were compared as sole carbon sources in 2% final concentration. Kerosene exhibited marked inhibition on the growth of the majority of the strains, whereas active growth was observed with Debaryomyces vanrijii and many species of the genus Candida in media with n-hexadecane or wax distillate as sole source of carbon. In addition, some cultures belonging to the genera Sporobolomyces, Hansenula, Cryptococcus, and Trigonopsis could utilize some of these substrates, but to a lesser extent. Highest yield of cells and protein was obtained with Candida lipolytica NRRL 1094 in n-hexadecane medium, supplied with 0.03% yeast extract and trace element solutions. The results are discussed with respect to the possibilities of using new yeast genera, with special reference to the genus Debaryomyces, in microbial protein production.
Harada, H; Katsuura, T; Kikuchi, Y
The present study was conducted to examine the optimum inter-key spacing of numeric rectangular keys for touch screens. Six male students (22-25 years old) and three female students (21-24 years old) participated in the experiment. Each subject performed the data entry task using rectangular keys of touch devices. These keys were arranged in both horizontal and vertical layouts. The sizes of the rectangular keys in both layouts were 12 x 21 mm and 15 x 39 mm, and each of the inter-key spacing of each key was 0, 3, 6, 12 and 21 mm. The response time with inter-key spacing of 3 mm was significantly faster than with the inter-key spacing of 0, 12 and 21 mm (p < 0.05). Keys of vertical position produced faster response time than that of horizontal position. The subjective ratings showed that the inter-key spacing of 6 mm was significantly better than the inter-key spacing of 0, 3, 12 and 21 mm (p < 0.05).
Full Text Available Background. The contribution of BRCA1 mutations to both hereditary and sporadic breast and ovarian cancer (HBOC has not yet been thoroughly investigated in MENA. Methods. To establish the knowledge about BRCA1 mutations and their correlation with the clinical aspect in diagnosed cases of HBOC in MENA populations. A systematic review of studies examining BRCA1 in BC women in Cyprus, Jordan, Egypt, Lebanon, Morocco, Algeria, and Tunisia was conducted. Results. Thirteen relevant references were identified, including ten studies which performed DNA sequencing of all BRCA1 exons. For the latter, 31 mutations were detected in 57 of the 547 patients ascertained. Familial history of BC was present in 388 (71% patients, of whom 50 were mutation carriers. c.798_799delTT was identified in 11 North African families, accounting for 22% of total identified BRCA1 mutations, suggesting a founder allele. A broad spectrum of other mutations including c.68_69delAG, c.181T>G, c.5095C>T, and c.5266dupC, as well as sequence of unclassified variants and polymorphisms, was also detected. Conclusion. The knowledge of genetic structure of BRCA1 in MENA should contribute to the assessment of the necessity of preventive programs for mutation carriers and clinical management. The high prevalence of BC and the presence of frequent mutations of the BRCA1 gene emphasize the need for improving screening programs and individual testing/counseling.
Paul J Leo
Full Text Available A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4% of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.
Full Text Available Asra R, Syamsuardi, Mansyurdin, Witono JR. 2014. The study of genetic diversity of Daemonorops draco (Palmae using ISSR markers. Biodiversitas 15: 109-114. The genetic diversity in five populations of Daemonorops draco(Willd. Blume (Jernang: in Bahasa Indonesia was analyzed using Inter Simple Sequence Repeat (ISSR markers. The screening results from using 15 ISSR primers showed that only 5 of ISSR primers had clear and reproducible bands. Based on the data from the matrix binary analyzed using POPGENE version 3.2, the highest genetic diversity was found in the Sepintun population at 0.0969 average heterozygosis (H and 0.146 average Shannon Index (I. The heterozygosis calculation of the total population (HT was 0.2571. The heterozygosis value within a population (HS=0.0704 was smaller than that between populations (DST=0.1867. Using the clustering analysis program Past version 32 on 43 individuals of D. draco, we found that there were three groups of D. draco. Group A consisted of 8 individuals in the Bengayoan population, group B consisted of 9 units in the Nunusan population and group C consisted of three populations; Tebo, Sepintun and Mandiangin consisted of 10, 8 and 8 individuals. The genetic similarity varied among all populations withthe values between 0.07-0.93.
Khan, Sarah; Woolhead, Gillian
Cervical cancer (CC) is the seventh leading cause of death among women in the United Arab Emirates (UAE), with most deaths attributed to late detection of this cancer. The UAE lacks a national CC screening programme. Thus, cervical screening is only performed opportunistically during women's visits to health facilities. CC screening rates in the UAE are as low as 16.9 %, and little is known about the perspectives of the nation's educated Muslim women regarding screening. Consequently, the aim of this study is to explore Muslim women's perspectives towards cervical screening in Dubai to promote strategies for increasing its uptake, thereby leading to a decrease in morbidity and mortality associated with CC. Interpretivist and social constructivist epistemological approaches were applied for this qualitative study. Data were obtained through 13 in-depth interviews. Purposive and snowballing methods were used to recruit six South Asian women and seven Emirati women living in Dubai. Thematic content analysis was concurrently applied with comparative analysis to the data. Four themes regarding women's perceptions of CC emerged from the data. First, CC was considered a 'silent disease' that could be detected with early screening. However, it was also associated with extramarital sexual relations, which negatively influenced screening uptake. Second, women's fear, pain and embarrassment, along with cultural influences, deterred them from undergoing screening. Third, a growing mistrust of allopathic medicine and impersonal healthcare promoted a negative view of screening. Last, women became aware of screening mainly when they were pregnant or receiving fertility treatment. The study highlighted a number of important factors relating to cultural, religious and sexual behaviour that shaped educated Muslim women's perspectives on CC screening. Evidently, the current opportunistic approach to screening is flawed. A national awareness programme on CC screening should be
Christensen, Kaare; McGue, Matt
The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...
In the present study, the effect of gamma irradiation was used in two Egyptian soybean cultivars; Giza-22 and Giza-82, to induce genetic variability with doses of 100, 150 and 200 Gy. Some agronomic characters were tested in M1 and M2 generations single plants. Oil and protein contents were measured from the resulted mutants of the two soybean cultivars at M2 generation. Some genetic parameters were estimated on the mean values of M2 generation. The results showed significant differences induced by gamma ray doses in all studied characters, particularly for 200 Gy in M1 generation. Gamma irradiation increased the genetic variability in M2 generation, which helped in selecting some high yielding mutants and some mutants with high oil and protein contents from the two cultivars. The estimated coefficients of phenotypic variance as well as coefficient of genotypic variance were high for seeds weight/plant, pod weight/plant, number of seeds/plant, number of pods/plant and number of nods/plant which showed better scope in genetic improvement. Heritability in the broad sense was high in most of the studied characters. The expected genetic advance (G.A) from selection was high for number of seeds, for number of pods, for pods weight and for mature plant height
Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: Efficient identification of known microduplications and identification of a novel microduplication in ASMT
Reichert Jennifer G
Full Text Available Abstract Background It has previously been shown that specific microdeletions and microduplications, many of which also associated with cognitive impairment (CI, can present with autism spectrum disorders (ASDs. Multiplex ligation-dependent probe amplification (MLPA represents an efficient method to screen for such recurrent microdeletions and microduplications. Methods In the current study, a total of 279 unrelated subjects ascertained for ASDs were screened for genomic disorders associated with CI using MLPA. Fluorescence in situ hybridization (FISH, quantitative polymerase chain reaction (Q-PCR and/or direct DNA sequencing were used to validate potential microdeletions and microduplications. Methylation-sensitive MLPA was used to characterize individuals with duplications in the Prader-Willi/Angelman (PWA region. Results MLPA showed two subjects with typical ASD-associated interstitial duplications of the 15q11-q13 PWA region of maternal origin. Two additional subjects showed smaller, de novo duplications of the PWA region that had not been previously characterized. Genes in these two novel duplications include GABRB3 and ATP10A in one case, and MKRN3, MAGEL2 and NDN in the other. In addition, two subjects showed duplications of the 22q11/DiGeorge syndrome region. One individual was found to carry a 12 kb deletion in one copy of the ASPA gene on 17p13, which when mutated in both alleles leads to Canavan disease. Two subjects showed partial duplication of the TM4SF2 gene on Xp11.4, previously implicated in X-linked non-specific mental retardation, but in our subsequent analyses such variants were also found in controls. A partial duplication in the ASMT gene, located in the pseudoautosomal region 1 (PAR1 of the sex chromosomes and previously suggested to be involved in ASD susceptibility, was observed in 6–7% of the cases but in only 2% of controls (P = 0.003. Conclusion MLPA proves to be an efficient method to screen for chromosomal
Waszak, Sebastian M; Northcott, Paul A; Buchhalter, Ivo; Robinson, Giles W; Sutter, Christian; Groebner, Susanne; Grund, Kerstin B; Brugières, Laurence; Jones, David T W; Pajtler, Kristian W; Morrissy, A Sorana; Kool, Marcel; Sturm, Dominik; Chavez, Lukas; Ernst, Aurelie; Brabetz, Sebastian; Hain, Michael; Zichner, Thomas; Segura-Wang, Maia; Weischenfeldt, Joachim; Rausch, Tobias; Mardin, Balca R; Zhou, Xin; Baciu, Cristina; Lawerenz, Christian; Chan, Jennifer A; Varlet, Pascale; Guerrini-Rousseau, Lea; Fults, Daniel W; Grajkowska, Wiesława; Hauser, Peter; Jabado, Nada; Ra, Young-Shin; Zitterbart, Karel; Shringarpure, Suyash S; De La Vega, Francisco M; Bustamante, Carlos D; Ng, Ho-Keung; Perry, Arie; MacDonald, Tobey J; Hernáiz Driever, Pablo; Bendel, Anne E; Bowers, Daniel C; McCowage, Geoffrey; Chintagumpala, Murali M; Cohn, Richard; Hassall, Timothy; Fleischhack, Gudrun; Eggen, Tone; Wesenberg, Finn; Feychting, Maria; Lannering, Birgitta; Schüz, Joachim; Johansen, Christoffer; Andersen, Tina V; Röösli, Martin; Kuehni, Claudia E; Grotzer, Michael; Kjaerheim, Kristina; Monoranu, Camelia M; Archer, Tenley C; Duke, Elizabeth; Pomeroy, Scott L; Shelagh, Redmond; Frank, Stephan; Sumerauer, David; Scheurlen, Wolfram; Ryzhova, Marina V; Milde, Till; Kratz, Christian P; Samuel, David; Zhang, Jinghui; Solomon, David A; Marra, Marco; Eils, Roland; Bartram, Claus R; von Hoff, Katja; Rutkowski, Stefan; Ramaswamy, Vijay; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Malkin, David; Gajjar, Amar; Korbel, Jan O; Pfister, Stefan M
Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Group3 ), and group 4 (MB Group4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105
Kingston, Dawn E; Biringer, Anne; McDonald, Sheila W; Heaman, Maureen I; Lasiuk, Gerri C; Hegadoren, Kathy M; McDonald, Sarah D; Veldhuyzen van Zanten, Sander; Sword, Wendy; Kingston, Joshua J; Jarema, Karly M; Vermeyden, Lydia; Austin, Marie-Paule
The process of mental health screening can influence disclosure, uptake of referral, and treatment; however, no studies have explored pregnant women's views of methods of mental health screening. The objectives of this study are to determine pregnant women's comfort and preferences regarding mental health screening. Pregnant women were recruited (May-December 2013) for this cross-sectional descriptive survey from prenatal classes and maternity clinics in Alberta, Canada, if they were aged >16 years and spoke/read English. Descriptive statistics summarized acceptability of screening, and multivariable logistic regression identified factors associated with women's comfort with screening methods. Analysis was conducted in January-December 2014. The participation rate was 92% (N=460/500). Overall, 97.6% of women reported that they were very (74.8%) or somewhat (22.8%) comfortable with mental health screening in pregnancy. Women were most comfortable with completing paper- (>90%) and computer-based (>82%) screening in a clinic or at home, with fewest reporting comfort with telephone-based screening (62%). The majority of women were very/somewhat comfortable with provider-initiated (97.4%) versus self-initiated (68.7%) approaches. Women's ability to be honest with their provider about emotional health was most strongly associated with comfort with each method of screening. The majority of pregnant women viewed prenatal mental health screening favorably and were comfortable with a variety of screening methods. These findings provide evidence of high acceptability of screening--a key criterion for implementation of universal screening--and suggest that providers can select from a variety of screening methods best suited for their clinical setting. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
Full Text Available Dystonias are heterogeneous hyperkinetic movement disorders characterized by involuntary muscle contractions which result in twisting, repetitive movements and abnormal postures. In recent years, there was a great advance in molecular genetic studies of primary dystonia. This paper will review the clinical characteristics and molecular genetic studies of primary dystonia, including early-onset generalized torsion dystonia (DYT1, whispering dysphonia (DYT4, dopa-responsive dystonia (DYT5, mixed-type dystonia (DYT6, paroxysmal kinesigenic dyskinesia (DYT10, myoclonus-dystonia syndrome (DYT11, rapid-onset dystonia parkinsonism (DYT12, adult-onset cervical dystonia (DYT23, craniocervical dystonia (DYT24 and primary torsion dystonia (DYT25.
I.A. Hoppenbrouwers (Ilse)
textabstractThe objective of this thesis was to find new risk alleles for MS. This may finally result in a better understanding of the pathogenesis of MS. Knowledge of MS disease pathways can direct strategies for prevention, diagnosis and therapy. In our study, we included MS patients from a
Delgado-Osorio, Héctor; Franqui-Rivera, Hilton; García-Palmieri, Mario R; Díaz-Santana, Mary V; Alvarez, Mario
Peripheral artery disease (PAD) of the lower extremities is frequently underdiagnosed and undertreated. The results of screening for PAD in adults attending outpatient clinics at different sites in Puerto Rico from 2007 to 2010 are presented. A total of 33 outpatients screening clinics were conducted at different sites throughout the Island. Following the ACC/AHA Guideline recommendations, asymptomatic patients who qualified were screened for PAD using the ankle-brachial index (ABI). An ABI diabetes mellitus, and dyslipidemia are known key factors in development of PAD. Practicing physicians must be aware of the importance of an early diagnosis of PAD, particularly in the asymptomatic patient, so as to institute preventive and management measures.
Most studies comparing full-field digital mammography (FFDM) with conventional screen-film mammography (SFM) have been radiology-based. The pathological implications of FFDM have received little attention in the literature, especially in the context of screening programmes. The primary objective of this retrospective study is to compare FFDM with SFM in a population-based screening programme with regard to a number of pathological parameters.
Pamjav, Horolma; Juhász, Zoltán; Zalán, Andrea; Németh, Endre; Damdin, Bayarlkhagva
Computer-aided comparison of folk music from different nations is one of the newest research areas. We were intrigued to have identified some important similarities between phylogenetic studies and modern folk music. First of all, both of them use similar concepts and representation tools such as multidimensional scaling for modelling relationship between populations. This gave us the idea to investigate whether these connections are merely accidental or if they mirror population migrations from the past. We raised the question; does the complex structure of musical connections display a clear picture and can this system be interpreted by the genetic analysis? This study is the first to systematically investigate the incidental genetic background of the folk music context between different populations. Paternal (42 populations) and maternal lineages (56 populations) were compared based on Fst genetic distances of the Y chromosomal and mtDNA haplogroup frequencies. To test this hypothesis, the corresponding musical cultures were also compared using an automatic overlap analysis of parallel melody styles for 31 Eurasian nations. We found that close musical relations of populations indicate close genetic distances (music; maternal lineages have a more important role in folk music traditions than paternal lineages. Furthermore, the combination of these disciplines establishing a new interdisciplinary research field of "music-genetics" can be an efficient tool to get a more comprehensive picture on the complex behaviour of populations in prehistoric time.
Mousseau, Timothy A; Møller, Anders P
Recent advances in genetic and ecological studies of wild animal populations in Chernobyl and Fukushima have demonstrated significant genetic, physiological, developmental, and fitness effects stemming from exposure to radioactive contaminants. The few genetic studies that have been conducted in Chernobyl generally show elevated rates of genetic damage and mutation rates. All major taxonomic groups investigated (i.e., birds, bees, butterflies, grasshoppers, dragonflies, spiders, mammals) displayed reduced population sizes in highly radioactive parts of the Chernobyl Exclusion Zone. In Fukushima, population censuses of birds, butterflies, and cicadas suggested that abundances were negatively impacted by exposure to radioactive contaminants, while other groups (e.g., dragonflies, grasshoppers, bees, spiders) showed no significant declines, at least during the first summer following the disaster. Insufficient information exists for groups other than insects and birds to assess effects on life history at this time. The differences observed between Fukushima and Chernobyl may reflect the different times of exposure and the significance of multigenerational mutation accumulation in Chernobyl compared to Fukushima. There was considerable variation among taxa in their apparent sensitivity to radiation and this reflects in part life history, physiology, behavior, and evolutionary history. Interestingly, for birds, population declines in Chernobyl can be predicted by historical mitochondrial DNA base-pair substitution rates that may reflect intrinsic DNA repair ability. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. [Morehouse Coll., Atlanta, GA (United States). School of Medicine; Crandall, L.A.; Moseley, R.E.; Armotrading, D. [Florida Univ., Gainesville, FL (United States). Coll. of Medicine
Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia`s system of Children`s Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.
Supriya Simon, A.; Dinesh Roy, D.; Jayapal, V.; Vijayakumar, T.
Cardiometabolic syndrome is one of the major public health issues of this century which describes a cluster of clinical characteristics. Seventy two patients with coronary artery disease (CAD) and cardiometabolic syndrome and forty healthy age and sex matched normal controls were selected for this study. Detailed clinical epidemiological and anthropometric characteristics were noted. Lipid profile and Cytokinesis-block micronuclei (CBMN) assay using cytochalasin B were carried out in all the ...
Barroso, R.C.; Eichler, J.; Lopes, R.T.; Cardoso, S.C.
To reduce the radiation dose in radiology, fluorescent intensifying screens for X-ray films are used. They produce visible light which increases the efficiency of the film. In addition, there are two other effects that will degrade the image resolution. First, the gadolinium present in the screens produces X-rays isotropically. Second, the primary radiation can be scattered elastically (Rayleigh scattering) and inelastically (Compton scattering). The intensity and angular distribution of these secondary radiation were measured, showing that the ratio of secondary-to-primary radiation incident on the X-ray film is about 16%. (orig.)
Reilly, Morgann C; Kim, Joonhoon; Lynn, Jed; Simmons, Blake A; Gladden, John M; Magnuson, Jon K; Baker, Scott E
Plant biomass, once reduced to its composite sugars, can be converted to fuel substitutes. One means of overcoming the recalcitrance of lignocellulose is pretreatment followed by enzymatic hydrolysis. However, currently available commercial enzyme cocktails are inhibited in the presence of residual pretreatment chemicals. Recent studies have identified a number of cellulolytic enzymes from bacteria that are tolerant to pretreatment chemicals such as ionic liquids. The challenge now is generation of these enzymes in copious amounts, an arena where fungal organisms such as Aspergillus niger have proven efficient. Fungal host strains still need to be engineered to increase production titers of heterologous protein over native enzymes, which has been a difficult task. Here, we developed a forward genetics screen coupled with whole-genome resequencing to identify specific lesions responsible for a protein hyper-production phenotype in A. niger. This strategy successfully identified novel targets, including a low-affinity glucose transporter, MstC, whose deletion significantly improved secretion of recombinant proteins driven by a glucoamylase promoter.
Reilly, Morgann C. [Joint BioEnergy Institute, Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kim, Joonhoon [Joint BioEnergy Institute, Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lynn, Jed [Joint BioEnergy Institute, Emeryville, CA (United States); Wright-Patterson Air Force Base, Dayton, OH (United States); Simmons, Blake A. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gladden, John M. [Joint BioEnergy Institute, Emeryville, CA (United States); Sandia National Lab. (SNL-CA), Livermore, CA (United States); Magnuson, Jon K. [Joint BioEnergy Institute, Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baker, Scott E. [Joint BioEnergy Institute, Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Plant biomass, once reduced to its composite sugars, can be converted to fuel substitutes. One means of overcoming the recalcitrance of lignocellulose is pretreatment followed by enzymatic hydrolysis. However, currently available commercial enzyme cocktails are inhibited in the presence of residual pretreatment chemicals. Recent studies have identified a number of cellulolytic enzymes from bacteria that are tolerant to pretreatment chemicals such as ionic liquids. The challenge now is generation of these enzymes in copious amounts, an arena where fungal organisms such as Aspergillus niger have proven efficient. Fungal host strains still need to be engineered to increase production titers of heterologous protein over native enzymes, which has been a difficult task. Here, we developed a forward genetics screen coupled with whole-genome resequencing to identify specific lesions responsible for a protein hyper-production phenotype in A. niger. This strategy successfully identified novel targets, including a low-affinity glucose transporter, MstC, whose deletion significantly improved secretion of recombinant proteins driven by a glucoamylase promoter.
The parents, F 1 , F 2 and backcrosses derived from triticale dwarf mutants and tall cultivars were studied during the 1979-80 crop season. Data was taken on individual plants to estimate dwarf inheritance, gene action and interrelationships of grain yield and selected yield related traits. The direct and indirect effects of grain yield per spike on other grain yield components were also studied. Results indicate that dwarfing is controlled by two, partially dominant, genes. Additional crosses involving other hexaploid triticale lines revealed the inheritance of other characters. The results in F 2 show that glossy plant, waxy covering of the neck and hairy neck are dominant, while short straw is recessive. Waxy covering on the spike seems to be controlled by two genes with additive action. Observation of F 2 progenies indicates that a gene for waxy neck covering Wx and hairy neck Hp might be located on the same chromosome at a distance of about 19 units. Plant height showed a positive phenotypic correlation with grain yield and 1,000 kernel weight. Non-significant correlations were found between plant height and number of grains per spike, harvest index and spikelet fertility. Path coefficient analyses at the phenotypic level indicated that the direct effects of grain number on grain yield were large while the direct effects of 1,000 kernel weight were relatively small. The results of this study indicate that selection for high kernel number is the most important factor in a breeding programme for increasing grain yield in some dwarf triticale. It was found that epistasis is not involved in the inheritance of harvest index. Additive, dominance and additive x dominance epistasis were important for grain yield per spike. A duplicate type of epistasis was found for 1,000 kernel weight and number of grains per spikelet. (author)
Al-Natour, A; Qandil, A; Gillespie, G L
To describe Jordanian nurses' roles and practices in screening for intimate partner violence. Intimate partner violence is a recognized global health problem with a prevalence of 37% for the Eastern Mediterranean region. Jordanian nurses screening for intimate partner violence is as low as 10.8%. Nurses have encountered institutional and personal barriers hindering their screening practice. A descriptive phenomenological design was used for this study. A purposive sample of 12 male and female Jordanian nurses working at a university hospital in Jordan participated. Participants were interviewed in 2014 using a semi-structured, face-to-face interview. Steps of Colaizzi's phenomenological method were used to analyse the qualitative data. Four themes were derived from the data: (1) screening practices and roles for suspected IPV cases, (2) advantages for screening and disadvantages for not screening for intimate partner violence, (3) factors hindering screening practice and (4) feelings towards screening and not screening for intimate partner violence. Increasing Jordanian nurses' awareness of the need for intimate partner violence screening in this sample was needed. Professional education and training may facilitate the adoption of intimate partner violence screening practices. A key barrier to intimate partner violence screening is Jordanian nurses' personal beliefs. Overcoming these personal beliefs will necessitate a multi-faceted approach starting with schools of nursing and bridging into healthcare settings. Healthcare professionals including nursing and policy makers at health institutions should enforce screening policies and protocols for all receipt of care at first contact. In addition, an emphasis on modelling culturally congruent approaches to develop the trusting nurse-patient relationships and process for screening patients for intimate partner violence. © 2016 International Council of Nurses.
Results published in the mid-1970s from the National Institute of Nutrition (NIN) in India showed increased numbers of polyploid cells in rats, mice, monkeys and malnourished children fed irradiated wheat products. This fact sheet considers the validity of these results. A large number of independent studies have been subsequently performed, and in none of these have results been obtained that support the NIN findings. The conclusion is that there is no evidence to link the consumption of irradiated food with any mutagenic effect. 3 refs
Zaveri, Kunal; Kiranmayi, Patnala
The prevalence of multi-drug resistance S. aureus is one of the most challenging tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. To screen the potential MurE inhibitor by in silico approach and evaluate the best potential lead molecule by in vitro methods. In the current study, we have employed structure based virtual screening targeting the active site of MurE, followed by Molecular dynamics and in vitro studies. Virtual screening resulted in successful screening of potential lead molecule ((2R)-2-[[1-[(2R)- 2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan). The molecular dynamics of the MurE and Lead molecule complex emphasizes that lead molecule has shown stable interactions with active site residues Asp 406 and with Glu 460. In vitro studies demonstrate that the lead molecule shows antibacterial activity close to standard antibiotic Vancomycin and higher than that of Ampicillin, Streptomycin and Rifampicin. The MIC of lead molecule at 50μg/mL was observed to be 3.75 μg/mL, MBC being bactericidal with value of 6.25 μg/mL, cytotoxicity showing 34.44% and IC50 of 40.06μg/mL. These results suggest ((2R)-2-[[1-[(2R)-2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan) as a promising lead molecule for developing a MurE inhibitor against treatment of S. aureus infections. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Russell, W.J.; Higashi, Yoshitaka; Fukuya, Tatsuro
To assess ultrasonography's capabilities in the detection of cancer and other diseases, abdominal ultrasonographic screening was performed for 3,707 Hiroshima and 2,294 Nagasaki atomic bomb survivors and comparison subjects who participated in the Adult Health Study from 1 November 1981 to 31 October 1985 in Hiroshima and from 1 August 1984 to 31 July 1986 in Nagasaki. A total of 20 cancers was detected, consisting of 7 hepatomas, 3 gastric cancers, 3 renal cancers, 2 cancers of the urinary bladder, and 1 cancer each of the ovary, pancreas, colon, ureter and liver (metastatic). The cancer detection rate was 0.33 %. The diagnoses of seven cancer subjects in each city were subsequently confirmed at autopsy or surgery; diagnoses of four cancer subjects in Hiroshima and two in Nagasaki were obtained from death certificates. Among the 20 cancer patients, 13 were asymptomatic. After the ultrasonographic detection and diagnosis of these 20 cancers, the medical records of each of the 20 cancer patients were reviewed for any evidence of cancer detection by other examining techniques, and the records of only 3 patients revealed such recent detection. The tumor and tissue registries were similarly checked, but no evidence of earlier diagnosis of their disease was found. Ten of the cancer patients had received ionizing radiation doses from the A-bombs ranging up to 3,421 mGy (DS86), but no correlation was established between cancer prevalence and the A-bomb doses. A variety of tumors, 259 in number and most probably benign, were also detected with ultrasonography. In addition, numerous other abnormalities were diagnosed, with prevalences of 7.7 % for cholelithiasis, 5.7 % for renal cysts, and 3.8 % for liver cysts. No statistical analysis was performed concerning the prevalence of the diseases detected. (author)
Genetic-linked Inattentiveness Protects Individuals from Internet Overuse: A Genetic Study of Internet Overuse Evaluating Hypotheses Based on Addiction, Inattention, Novelty-seeking and Harm-avoidance
Full Text Available The all-pervasive Internet has created serious problems, such as Internet overuse, which has triggered considerable debate over its relationship with addiction. To further explore its genetic susceptibilities and alternative explanations for Internet overuse, we proposed and evaluated four hypotheses, each based on existing knowledge of the biological bases of addiction, inattention, novelty-seeking, and harm-avoidance. Four genetic loci including DRD4 VNTR, DRD2 Taq1A, COMT Val158Met and 5-HTTLPR length polymorphisms were screened from seventy-three individuals. Our results showed that the DRD4 4R/4R individuals scored significantly higher than the 2R or 7R carriers in Internet Addiction Test (IAT. The 5-HTTLPR short/short males scored significantly higher in IAT than the long variant carriers. Bayesian analysis showed the most compatible hypothesis with the observed genetic results was based on attention (69.8%, whereas hypotheses based harm-avoidance (21.6%, novelty-seeking (7.8% and addiction (0.9% received little support. Our study suggests that carriers of alleles (DRD4 2R and 7R, 5-HTTLPR long associated with inattentiveness are more likely to experience disrupted patterns and reduced durations of Internet use, protecting them from Internet overuse. Furthermore, our study suggests that Internet overuse should be categorized differently from addiction due to the lack of shared genetic contributions.
Reeder, Rebecca; Veach, Patricia McCarthy; MacFarlane, Ian M; LeRoy, Bonnie S
Countertransference (CT) refers to conscious and unconscious emotions, fantasies, behaviors, perceptions, and psychological defenses genetic counselors experience in response to any aspect of genetic counseling situations (Weil 2010). Some authors theorize about the importance of recognizing and managing CT, but no studies solely aim to explore genetic counselors' experiences of the phenomenon. This study examined the extent to which clinical genetic counselors' perceive themselves as inclined to experience CT, gathered examples of CT encountered in clinical situations, and assessed their CT management strategies. An anonymous online survey, sent to NSGC members, yielded 127 usable responses. Participants completed Likert-type items rating their CT propensities; 57 of these individuals also provided examples of CT they experienced in their practice. Factor analysis of CT propensities tentatively suggested four factors: Control, Conflict Avoidance, Directiveness, and Self-Regulation, accounting for 38.5% of response variance. Thematic analysis of CT examples yielded five common triggers: general similarity to patient, medical/genetic similarity, angry patients, patient behaves differently from counselor expectations, and disclosing bad news; six common manifestations: being self-focused, projecting feelings onto the patient, intense emotional reaction to patient, being overly invested, disengagement, and physical reaction; five CT effects: disruption in rapport building, repaired empathy, over-identification, conversation does not reach fullest potential, and counselor is drained emotionally; and three management strategies: recognizing CT as it occurs, self-reflection, and consultation. Results suggest CT is a common experience, occurring in both "routine" and emotionally complex cases. Training programs, continuing education, and peer supervision might include discussion of CT, informed by examples from the present study, to increase genetic counselor awareness
Poirier, Catherine Serra; Brendgen, Mara; Girard, Alain; Vitaro, Frank; Dionne, Ginette; Boivin, Michel
This study examined (a) whether, in line with a gene-environment correlation (rGE), a genetic disposition for anxiety puts children at risk of having anxious friends or having no reciprocal friends; (b) to what extent these friendship experiences are related to anxiety symptoms, when controlling for sex and genetic disposition for this trait; and (c) the additive and interactive predictive links of the reciprocal best friend's anxiety symptoms and of friendship quality with children's anxiety symptoms. Using a genetically informed design based on 521 monozygotic and ic twins (264 girls; 87% of European descent) assessed in Grade 4 (M age = 10.04 years, SD = .26), anxiety symptoms and perceived friendship quality were measured with self-report questionnaires. Results indicated that, in line with rGE, children with a strong genetic disposition for anxiety were more likely to have anxious friends than nonanxious friends. Moreover, controlling for their genetic risk for anxiety, children with anxious friends showed higher levels of anxiety symptoms than children with nonanxious friends but did not differ from those without reciprocal friends. Additional analyses suggested a possible contagion of anxiety symptoms between reciprocal best friends when perceived negative features of friendship were high. These results underline the importance of teaching strategies such as problem solving that enhance friendship quality to limit the potential social contagion of anxiety symptoms.
Maňáková, E.; Hubičková, L.; Košťálová, J.; Zemanová, Zdeňka
Roč. 31, Suppl.2 (2010), s. 8-10 ISSN 0172-780X Institutional research plan: CEZ:AV0Z50110509 Keywords : embryo toxicity * screening test * mirtazapine Subject RIV: EA - Cell Biology Impact factor: 1.621, year: 2010
Sarmiento Campos, Jose A.; Squires, Jane; Ponte, Jaime
"A_Tempo" is a research project that is currently under development in Galicia, an autonomous community of Spain. Its main aim is to propose an effective universal screening procedure for early identification of developmental disorders in children from zero to three years of age who attend Galician pre-primary schools.…
In India, it is one the leading causes of mortality among women accounting for ... Knowledge about cervical cancer, its screening among women. • Role of health ..... by health professional [14 (16.9)], lack of time [4 (4.8)], fear of having a bad ...
Kurbatova, O L; Pobedonostseva, E Iu; Prokhorovskaia, V D; Kholod, O N; Evsiukov, A N; Bogomolov, V V; Voronkov, Iu I; Filatova, L M; Larina, O N; Sidorenko, L A; Morgun, V V; Kasparanskiĭ, R R; Altukhov, Iu P
Genetic demographic characteristics and immunogenetic markers (blood groups ABO, Rhesus, MNSs, P, Duffy, Kidd, and Kell) have been studied in a group of 132 Russian cosmonauts and test subjects (CTSG). Analysis of pedigrees has shown a high exogamy in the preceding generations: almost half of the subjects have mixed ethnic background. According to the results of genetic demographic analysis, a sample from the Moscow population was used as control group (CG). Comparison between the CTSG and CG has demonstrated significant differences in genotype frequencies for several blood group systems. The CTSG is characterized by a decreased proportion of rare interlocus genotypic combinations and an increased man heterozygosity. Analysis of the distributions of individual heterozygosity for loci with codominant expression of alleles has shown that highly heterozygous loci are more frequent in the CTSG. Taking into account that the CTSG has been thoroughly selected from the general population, it is concluded that heterozygosity is related to successful adaptation to a space flight.
Tan, Qihua; Li, Weilong; Vandin, Fabio
and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient...... concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases...... population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size...
Jelsig, Anne Marie
the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing. Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps...... appearance. Patients with one or a few juvenile polyps are usually not offered clinical follow-up as the polyp(s) are considered not to harbour any malignant potential. Nevertheless, it is important to note that juvenile polyps and HPs are also found in patients with hereditary hamartomatous polyposis......-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand...
Full Text Available About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net, to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions.
Full Text Available Improving accuracy in genetic studies would greatly accelerate understanding the genetic basis of complex diseases. One approach to achieve such an improvement for risk variants identified by the genome wide association study (GWAS approach is to incorporate previously known biology when screening variants across the genome. We developed a simple approach for improving the prioritization of candidate disease genes that incorporates a network diffusion of scores from known disease genes using a protein network and a novel integration with GWAS risk scores, and tested this approach on a large Alzheimer disease (AD GWAS dataset. Using a statistical bootstrap approach, we cross-validated the method and for the first time showed that a network approach improves the expected replication rates in GWAS studies. Several novel AD genes were predicted including CR2, SHARPIN, and PTPN2. Our re-prioritized results are enriched for established known AD-associated biological pathways including inflammation, immune response, and metabolism, whereas standard non-prioritized results were not. Our findings support a strategy of considering network information when investigating genetic risk factors.
Hryshchenko, N V; B'ichkova, A M; Lyvshyts, A B; Kravchenko, S A; Pampukha, V N; Solov'ev, A A; Kucherenko, A M; Tatarskiĭ, P F; Afanas'eva, N A; Dubrovskaia, E V; Patskun, Ie Y; Zymak-Zakutnaia, N O; Nykytchina, T V; Lohysh, S Iu; Lyvshyts, L A
The results of clinical, genealogical, cytogenetic and molecular genetic studies of 113 patients from 96 families with different forms of mental retardation from Ukraine are presented. This study was held as part of the CHERISH project of the 7-th Framework Program. The aim of the project is to improve diagnostics of mental retardation in children in Eastern Europe and Central Asia through detailed analysis of known chromosomal and gene's aberrations and to find the new gene-candidates that cause mental retardation. All patients have normal chromosome number (46XY or 46XX). The cases with fragile-X syndrome were eliminated using molecular genetic methods. Genome rearrangements were found among 28 patients using cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA analysis) ofsubtelomeric regions and array-based comparative genomic hybridisation (array CGH screening). In 10 cases known pathogenic CNV's were identified, 11 cases are unknown aberrations; their pathogenicity is being determined. The rest cases are known nonpathogenic gene rearrangements. Obtained results show the strong genetic heterogeneity of hereditary forms of mental retardation. The further studies will allow to identificate genes candidates and certain mutations in these genes that may be associated with this pathology.
Rivera, B; González, S; Sánchez-Tomé, E; Blanco, I; Mercadillo, F; Letón, R; Benítez, J; Robledo, M; Capellá, G; Urioste, M
Classical familial adenomatous polyposis (FAP) is characterized by the appearance of >100 colorectal adenomas. We screened the APC and MUTYH genes for mutations and evaluated the genotype-phenotype correlation in 136 Spanish classical FAP families. APC/MUTYH mutations were detected in 107 families. Sixty-four distinct APC point mutations were detected in 95 families of which all were truncating mutations. A significant proportion (39.6%) had not been previously reported. Mutations were spread over the entire coding region and great rearrangements were identified in six families. Another six families exhibited biallelic MUTYH mutations. No APC or MUTYH mutations were detected in 29 families. These APC/MUTYH-negative families showed clinical differences with the APC-positive families. A poor correlation between phenotype and mutation site was observed. Our results highlight that a broad approach in the genetic study must be considered for classical FAP due to involvement of both APC and MUTYH and the heterogeneous spectrum of APC mutations observed in this Spanish population. The scarcely consistent genotype-phenotype correlation does not allow making specific recommendations regarding screening and management. Differences observed in APC/MUTYH-negative families may reflect a genetic basis other than mutations in APC and MUTYH genes for FAP predisposition. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
In the present study, we tested rice genotypes that included un(der)exploited landraces of Tamil Nadu along with indica and japonica test cultivars to ascertain their genetic diversity structure. Highly polymorphic microsatellite markers were used for generating marker segregation data. A novel measure, allele discrimination ...
Gasparini, Claudia F; Sutherland, Heidi G.; Griffiths, Lyn R
Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies. PMID:24403849
Bivariate and multivariate analyses fitting an animal model, were conducted by means of (ASREML) ... aggregate genetic improvement in beef cattle is most ..... This trend was observed in the present study. .... effects hence the prediction of correlated responses to ... the shape of the growth curve as an animal can be.
Go, S.L.; Hoyng, C.B.; Klaver, C.C.W.
OBJECTIVE: To investigate the magnitude of the genetic risk of nonsyndromic rhegmatogenous retinal detachments (RRDs) in a familial aggregation study. DESIGN: Two hundred three consecutive patients with RRD and 461 controls without RRD were ascertained at the Department of Ophthalmology of the
S.L. Go (Sioe Lie); C. Hoyng (Carel); C.C.W. Klaver (Caroline)
textabstractObjective: To investigate the magnitude of the genetic risk of nonsyndromic rhegmatogenous retinal detachments (RRDs) in a familial aggregation study. Design: Two hundred three consecutive patients with RRD and 461 controls without RRD were ascertained at the Department of Ophthalmology
This study investigated comparatively the genetic influence on the susceptibility of exotic cockerels, pullets and broilers to natural infection with infectious bursal disease (IBD) virus in a flock of 150 seven-week-old exotic breed of chickens comprising of 50 Black Harco cockerels, 50 Black Harco pullets and 50 White ...
Iebba, Filippo; Di Sora, Fiorella; Leti, Wilma; Montella, Tatiana; Montella, Francesco
We report on the HLA typing of three brothers (A, B, C) with rheumatoid arthritis (RA) and their six sons. This family is interesting for the full concordance for RA between parents. The aim of this study was the discovery of genetic and/or enviromental cofactors determining this absolute concordance.
study. Onyilagha (1988) used polyacrylamide gel elctrophoresis on 13 cultivars of Dioscorea (5 of D.rotundata and 8 of D.cayenesis). The two taxa have some common morphological features, leading to .... g, potassium chloride = 0.725 g, ethylene ..... feasibility in broadening the genetic base for the improvement of yam.
Paap, Ellen; Verbeek, André L. M.; Botterweck, Anita A. M.; van Doorne-Nagtegaal, Heidi J.; Imhof-Tas, Mechli; de Koning, Harry J.; Otto, Suzie J.; de Munck, Linda; van der Steen, Annemieke; Holland, Roland; den Heeten, Gerard J.; Broeders, Mireille J. M.
Large-scale epidemiologic studies have consistently demonstrated the effectiveness of mammographic screening programs, however the benefits are still subject to debate. We estimated the effect of the Dutch screening program on breast cancer mortality. In a large multi-region case-referent study, we
Howard, TD; Wiesch, DG; Koppelman, GH; Postma, DS; Meyers, DA; Bleecker, ER
Allergy and asthma are closely related complex diseases caused by a combination of both genetic and environmental influences. Two common genetic approaches, candidate gene studies and genome-wide screens, have been used to localize and evaluate potential genetic factors that confer susceptibility or
Moran, S.; Warren-Forward, H.
Purpose: This paper provides data on the continued success of radiographers in reviewing mammograms with similar accuracy to screen readers. Method: The participants consisted of 7 radiographers and 2 current official screen readers. Two hundred and fifty sets of mammograms from 2003 were used in this study. Each participant reviewed each set of mammograms as a Rescreen or Recall. Patient outcomes were assessed by following up the results of any histology or pathology tests in 2003 or the 2005/2006 screening results. Results: The screen reader's sensitivities ranged from 79% to 93% and the specificities ranged from 82% to 84%. The radiographer values ranged from 57% to 97% and 63% to 80% respectively. Conclusion: The sensitivity and specificity values attained by some radiographers were equivalent to those of both the screen readers. Accuracy rates of the radiographers suggest that screen reading by selected and appropriately trained radiographers should be achievable in Australia.
... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...
This presentation will consider approaches to discover susceptibility genes for a complex genetic disorder such as preeclampsia. The clinical disease presumably results from the additive effects of multiple sequence variants from the mother and the foetus together with environmental factors. Disease heterogeneity and underpowered study designs are likely to be behind non-reproducible results in candidate gene association studies. To avoid spurious findings, sample size and characteristics of the study populations as well as replication studies in an independent study population should be an essential part of a study design. In family-based linkage studies relationship with genotype and phenotype may be modified by a variety of factors. The large number of families needed in discovering genetic variants with modest effect sizes is difficult to attain. Moreover, the identification of underlying mutations has proven difficult. When pooling data or performing meta-analyses from different populations, disease and locus heterogeneity may become a major issue. First genome-wide association studies (GWAS) have identified risk loci for preeclampsia. Adequately powered replication studies are critical in order to replicate the initial GWAS findings. This approach requires rigorous multiple testing correction. The expected effect sizes of individual sequence variants on preeclampsia are small, but this approach is likely to decipher new clues to the pathogenesis. The rare variants, gene-gene and gene-environmental interactions as well as noncoding genetic variations and epigenetics are expected to explain the missing heritability. Next-generation sequencing technologies will make large amount of data on genomes and transcriptomes available. Complexity of the data poses a challenge. Different depths of coverage might be chosen depending on the design of the study, and validation of the results by different methods is mandatory. In order to minimize disease heterogeneity in
Van't Hoog, Anna H; Onozaki, Ikushi; Lonnroth, Knut
To inform the choice of an appropriate screening and diagnostic algorithm for tuberculosis (TB) screening initiatives in different epidemiological settings, we compare algorithms composed of currently available methods. Of twelve algorithms composed of screening for symptoms (prolonged cough or any TB symptom) and/or chest radiography abnormalities, and either sputum-smear microscopy (SSM) or Xpert MTB/RIF (XP) as confirmatory test we model algorithm outcomes and summarize the yield, number needed to screen (NNS) and positive predictive value (PPV) for different levels of TB prevalence. Screening for prolonged cough has low yield, 22% if confirmatory testing is by SSM and 32% if XP, and a high NNS, exceeding 1000 if TB prevalence is ≤0.5%. Due to low specificity the PPV of screening for any TB symptom followed by SSM is less than 50%, even if TB prevalence is 2%. CXR screening for TB abnormalities followed by XP has the highest case detection (87%) and lowest NNS, but is resource intensive. CXR as a second screen for symptom screen positives improves efficiency. The ideal algorithm does not exist. The choice will be setting specific, for which this study provides guidance. Generally an algorithm composed of CXR screening followed by confirmatory testing with XP can achieve the lowest NNS and highest PPV, and is the least amenable to setting-specific variation. However resource requirements for tests and equipment may be prohibitive in some settings and a reason to opt for symptom screening and SSM. To better inform disease control programs we need empirical data to confirm the modeled yield, cost-effectiveness studies, transmission models and a better screening test.
Ivan de Carlos Cáceres
Full Text Available C. elegans is an excellent model system for studying neuroscience using genetics because of its relatively simple nervous system, sequenced genome, and the availability of a large number of transgenic and mutant strains. Recently, microfluidic devices have been used for high-throughput genetic screens, replacing traditional methods of manually handling C. elegans. However, the orientation of nematodes within microfluidic devices is random and often not conducive to inspection, hindering visual analysis and overall throughput. In addition, while previous studies have utilized methods to bias head and tail orientation, none of the existing techniques allow for orientation along the dorso-ventral body axis. Here, we present the design of a simple and robust method for passively orienting worms into lateral body positions in microfluidic devices to facilitate inspection of morphological features with specific dorso-ventral alignments. Using this technique, we can position animals into lateral orientations with up to 84% efficiency, compared to 21% using existing methods. We isolated six mutants with neuronal development or neurodegenerative defects, showing that our technology can be used for on-chip analysis and high-throughput visual screens.
Thamsborg, Lise Holst; Andersen, Berit; Larsen, Lise Grupe; Christensen, Jette; Johansen, Tonje; Hariri, Jalil; Christiansen, Sanne; Rygaard, Carsten; Lynge, Elsebeth
The first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated women. These women are better protected against cervical cancer and could therefore be offered less intensive screening. Primary HPV testing is more sensitive than cytology, allowing for a longer screening interval. The aim of Trial23 is to investigate if primary HPV testing with cytology triage of HPV positive samples is a reasonable screening scheme for women offered HPV vaccination as girls. Trial23 is a method study embedded in the existing cervical screening programme in four out of five Danish regions. Without affecting the screening programme, women born in 1994 are randomised to present screening with liquid-based cytology every third year (present programme arm) or present screening plus an HPV test (HPV arm). The study started 1 February 2017 and will run over three screening rounds corresponding to 7-8 years. The primary endpoint is cervical intraepithelial neoplasia grade 3 or above. The trial is undertaken as a non-inferiority study including intention-to-treat and per-protocol analyses. The potential effect of primary HPV screening with a 6-year interval will be calculated from the observed data. The study protocol has been submitted to the ethical committee and deemed a method study. All women are screened according to routine guidelines. The study will contribute new evidence on the future screening of HPV vaccinated birth cohorts of women. All results will be published in open-access journal. NCT03049553; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Livingstone, Mark; Larsson, Ola; Sukarieh, Rami; Pelletier, Jerry; Sonenberg, Nahum
The signal transduction pathway wherein mTOR regulates cellular growth and proliferation is an active target for drug discovery. The search for new mTOR inhibitors has recently yielded a handful of promising compounds that hold therapeutic potential. This search has been limited by the lack of a high-throughput assay to monitor the phosphorylation of a direct rapamycin-sensitive mTOR substrate in cells. Here we describe a novel cell-based chemical genetic screen useful for efficiently monitoring mTOR signaling to 4E-BPs in response to stimuli. The screen is based on the nuclear accumulation of eIF4E, which occurs in a 4E-BP-dependent manner specifically upon inhibition of mTOR signaling. Using this assay in a small-scale screen, we have identified several compounds not previously known to inhibit mTOR signaling, demonstrating that this method can be adapted to larger screens. Copyright 2009 Elsevier Ltd. All rights reserved.
Cohen, Stacey A; Laurino, Mercy; Bowen, Deborah J; Upton, Melissa P; Pritchard, Colin; Hisama, Fuki; Jarvik, Gail; Fichera, Alessandro; Sjoding, Britta; Bennett, Robin L; Naylor, Lorraine; Jacobson, Angela; Burke, Wylie; Grady, William M
Lynch syndrome confers a hereditary predisposition to colorectal and other cancers. Universal tumor screening (UTS) for Lynch syndrome is recommended by several professional societies, but the implementation can be complex. This article describes the evaluation, process development, and initiation of Lynch syndrome UTS at a tertiary referral cancer center. A multidisciplinary team developed the new process design. Issues in 5 themes were noted: timing, funding, second-opinion patients, result processing, and the role of genetics providers. A committee approach was used to examine each issue for process-improvement development. The issues related to testing were addressed individually for the successful implementation of UTS at the institutional level. In the conventional-care period, 9 of 30 cases (30%) received Lynch syndrome screening, and 4 cases were referred to medical genetics. During the 6 months following the implementation of UTS, 32 of 44 patients (73%) received Lynch syndrome screening. The 13 unscreened patients all had identified reasons for nonscreening (eg, financial limitations). Ten patients were referred to medical genetics, which identified no new cases of Lynch syndrome, but a low-risk adenomatous polyposis coli (APC) variant was detected in 1 individual. The implementation of effective Lynch syndrome UTS can feasibly alter practice at the institutional level. This experience with the assessment and management of issues relevant to the successful implementation of a new clinical care paradigm based on emerging technology has implications for the uptake of advances across molecular oncology into clinical practice, and this is highly relevant in the current era of rapidly evolving genomic technology. © 2015 American Cancer Society.
Production environments are expected to change, mostly to a hotter climate but also possibly more extreme and drier. Can the current generation of farm animals cope with the changes or should it be specifically selected for changing conditions? In general, genetic selection produces animals with a smaller environmental footprint but also with smaller environmental flexibility. Some answers are coming from heat-stress research across species, with heat tolerance partly understood as a greater environmental flexibility. Specific studies in various species show the complexities of defining and selecting for heat tolerance. In Holsteins, the genetic component for effect of heat stress on production approximately doubles in second and quadruples in third parity. Cows with elevated body temperature have the greatest production under heat stress but probably are at risk for increased mortality. In hot but less intensive environments, the effect of heat stress on production is minimal, although the negative effect on fertility remains. Mortality peaks under heat stress and increases with parity. In Angus, the effect of heat stress is stronger only in selected regions, probably because of adaptation of calving seasons to local conditions and crossbreeding. Genetically, the direct effect shows variability because of heat stress, but the maternal effect does not, probably because dams shield calves from environmental challenges. In pigs, the effect of heat stress is strong for commercial farms but almost nothing for nucleus farms, which have lower pig density and better heat abatement. Under intensive management, heat stress is less evident in drier environments because of more efficient cooling. A genetic component of heat stress exists, but it is partly masked by improving management and selection based on data from elite farms. Genetic selection may provide superior identification of heat-tolerant animals, but a few cycles may be needed for clear results. Also, simple
van der Vleuten Cees
Full Text Available Abstract Background Available evidence suggests that improvements in genetics education are needed to prepare primary care providers for the impact of ongoing rapid advances in genomics. Postgraduate (physician training and master (midwifery training programmes in primary care and public health are failing to meet these perceived educational needs. The aim of this study was to explore the role of genetics in primary care (i.e. family medicine and midwifery care and the need for education in this area as perceived by primary care providers, patient advocacy groups and clinical genetics professionals. Methods Forty-four participants took part in three types of focus groups: mono-disciplinary groups of general practitioners and midwives, respectively and multidisciplinary groups composed of a diverse set of experts. The focus group sessions were audio-taped, transcribed verbatim and analysed using content analysis. Recurrent themes were identified. Results Four themes emerged regarding the educational needs and the role of genetics in primary care: (1 genetics knowledge, (2 family history, (3 ethical dilemmas and psychosocial effects in relation to genetics and (4 insight into the organisation and role of clinical genetics services. These themes reflect a shift in the role of genetics in primary care with implications for education. Although all focus group participants acknowledged the importance of genetics education, general practitioners felt this need more urgently than midwives and more strongly emphasized their perceived knowledge deficiencies. Conclusion The responsibilities of primary care providers with regard to genetics require further study. The results of this study will help to develop effective genetics education strategies to improve primary care providers' competencies in this area. More research into the educational priorities in genetics is needed to design courses that are suitable for postgraduate and master programmes for
Doris Y. P. Leung
Full Text Available Colorectal cancer (CRC is a major health problem in Asia. It has been reported that the Chinese are more susceptible to CRC than many other ethnic groups. Screening for CRC is a cost-effective prevention and control strategy; however, the screening rates among the Chinese are sub-optimal. We conducted a review to identify the factors associated with CRC screening participation among Chinese people. Twenty-two studies that examined the factors related to CRC screening behaviors among the Chinese were identified through five databases. Seven factors were consistently reported to influence CRC screening behaviors in at least one of the studies: socio-demographic characteristics (educational level, health insurance, and knowledge about CRC and its screening; psychological factors (perceived severity of CRC, susceptibility of having CRC, and barriers to screening; and contact with medical provider (physician recommendation. The evidence base for many of these relationships is quite limited. Furthermore, the associations of many factors, including age, gender, income, cancer worry/fear, and self-efficacy with CRC screening behaviors, were mixed or inconsistent across these studies, thereby indicating that more studies are needed in this area.
Reynolds, Fiona; Stanistreet, Debbi; Elton, Peter
Background Several studies in the UK have suggested that women with learning disabilities may be less likely to receive cervical screening tests and a previous local study in had found that GPs considered screening unnecessary for women with learning disabilities. This study set out to ascertain whether women with learning disabilities are more likely to be ceased from a cervical screening programme than women without; and to examine the reasons given for ceasing women with learning disabilities. It was carried out in Bury, Heywood-and-Middleton and Rochdale. Methods Carried out using retrospective cohort study methods, women with learning disabilities were identified by Read code; and their cervical screening records were compared with the Call-and-Recall records of women without learning disabilities in order to examine their screening histories. Analysis was carried out using case-control methods – 1:2 (women with learning disabilities: women without learning disabilities), calculating odds ratios. Results 267 women's records were compared with the records of 534 women without learning disabilities. Women with learning disabilities had an odds ratio (OR) of 0.48 (Confidence Interval (CI) 0.38 – 0.58; X2: 72.227; p.value learning disabilities. Conclusion The reasons given for ceasing and/or not screening suggest that merely being coded as having a learning disability is not the sole reason for these actions. There are training needs among smear takers regarding appropriate reasons not to screen and providing screening for women with learning disabilities. PMID:18218106
Field, John K.; Smith, Robert A.; Aberle, Denise R.; Oudkerk, Matthijs; Baldwin, David R.; Yankelevitz, David; Pedersen, Jesper Holst; Swanson, Scott James; Travis, William D.; Wisbuba, Ignacio I.; Noguchi, Masayuki; Mulshine, Jim L.
The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer
Jørgensen, F S; Valentin, L; Salvesen, K A
AIM: To study the detection rates of second trimester ultrasound screening for neural tube defects (NTD), abdominal wall defects (AWD) and Down's syndrome (DS) in low risk populations at tertiary centers, and to compare the ultrasound screening detection rates with those that were obtainable by b...
Blecic, Deborah D.; Dorsch, Josephine L.; Koenig, Melissa H.; Bangalore, Nimala S.
Describes a longitudinal study of four sets of OPAC (online public access catalog) transaction logs that examined the effects of screen changes in helping searchers improve their search behavior. Results show that while screen changes initially had a positive impact on search behavior, they were not always sustained over time. (Author/LRW)
Dimou, Niki L; Pantavou, Katerina G; Braliou, Georgia G; Bagos, Pantelis G
Multivariate meta-analysis of genetic association studies and genome-wide association studies has received a remarkable attention as it improves the precision of the analysis. Here, we review, summarize and present in a unified framework methods for multivariate meta-analysis of genetic association studies and genome-wide association studies. Starting with the statistical methods used for robust analysis and genetic model selection, we present in brief univariate methods for meta-analysis and we then scrutinize multivariate methodologies. Multivariate models of meta-analysis for a single gene-disease association studies, including models for haplotype association studies, multiple linked polymorphisms and multiple outcomes are discussed. The popular Mendelian randomization approach and special cases of meta-analysis addressing issues such as the assumption of the mode of inheritance, deviation from Hardy-Weinberg Equilibrium and gene-environment interactions are also presented. All available methods are enriched with practical applications and methodologies that could be developed in the future are discussed. Links for all available software implementing multivariate meta-analysis methods are also provided.
Thanh T Hoang
Full Text Available The Pediatric Cardiac Genomics Consortium (PCGC designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs cohort. This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome. Cases with CHDs were recruited through ten sites, 2010-2014. Information on cases (N = 9,727 and their parents was collected through interviews and medical record abstraction. Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes. Eleven percent of cases had a genetic diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40% or left ventricular outflow tract obstruction (21%. Across CHD types, there were significant differences (p<0.05 in the distribution of all four case characteristics (e.g., sex, four parental characteristics (e.g., maternal pregestational diabetes, and five neurodevelopmental outcomes (e.g., learning disabilities. Several characteristics (e.g., sex were also significantly different across CHD subtypes. The PCGC cohort is one of the largest CHD cohorts available for the study of genetic determinants of risk and outcomes. The majority of cases do not have a genetic diagnosis. This description of the PCGC cohort, including differences across CHD types and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC.
Lynge, Elsebeth; Beau, Anna-Belle; Christiansen, Peer; von Euler-Chelpin, My; Kroman, Niels; Njor, Sisse; Vejborg, Ilse
Overdiagnosis in breast cancer screening is an important issue. A recent study from Denmark concluded that one in three breast cancers diagnosed in screening areas in women aged 50-69 years were overdiagnosed. The purpose of this short communication was to disentangle the study's methodology in order to evaluate the soundness of this conclusion. We found that both the use of absolute differences as opposed to ratios; the sole focus on non-advanced tumours and the crude allocation of tumours and person-years by screening history for women aged 70-84 years, all contributed to the very high estimate of overdiagnosis. Screening affects cohorts of screened women. Danish registers allow very accurate mapping of the fate of every woman. We should be past the phase where studies of overdiagnosis are based on the fixed age groups from routine statistics. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Fletcher Robert H
Full Text Available Abstract Background Colorectal cancer screening rates are low among disadvantaged patients; few studies have explored barriers to screening in community health centers. The purpose of this study was to describe barriers to/facilitators of colorectal cancer screening among diverse patients served by community health centers. Methods We identified twenty-three outpatients who were eligible for colorectal cancer screening and their 10 primary care physicians. Using in-depth semi-structured interviews, we asked patients to describe factors influencing their screening decisions. For each unscreened patient, we asked his or her physician to describe barriers to screening. We conducted patient interviews in English (n = 8, Spanish (n = 2, Portuguese (n = 5, Portuguese Creole (n = 1, and Haitian Creole (n = 7. We audiotaped and transcribed the interviews, and then identified major themes in the interviews. Results Four themes emerged: 1 Unscreened patients cited lack of trust in doctors as a barrier to screening whereas few physicians identified this barrier; 2 Unscreened patients identified lack of symptoms as the reason they had not been screened; 3 A doctor's recommendation, or lack thereof, significantly influenced patients' decisions to be screened; 4 Patients, but not their physicians, cited fatalistic views about cancer as a barrier. Conversely, physicians identified competing priorities, such as psychosocial stressors or comorbid medical illness, as barriers to screening. In this culturally diverse group of patients seen at community health centers, similar barriers to screening were reported by patients of different backgrounds, but physicians perceived other factors as more important. Conclusion Further study of these barriers is warranted.
Jing, Shuang; Luo, Keli; He, Hui; Lu, Changfu; Zhang, Shuoping; Tan, Yueqiu; Gong, Fei; Lu, Guangxiu; Lin, Ge
To study whether embryo biopsy for preimplantation genetic diagnosis/preimplantation genetic screening (PGD/PGS) can influence pregnancy complications and neonatal outcomes. Retrospective analysis. University-affiliated center. This study included data from women and their neonates born after PGD/PGS (n = 317). Questionnaires were designed to obtain information relating to pregnancy complications and neonatal outcomes. Two major strategies for PGD/PGS were evaluated. Blastocyst-stage biopsy and frozen embryo transfer (BB-FET) was carried out in 166 patients, and cleavage-stage biopsy and fresh embryo transfer (CB-ET) was carried out in 129 patients. The incidence of gestational hypertension was significantly higher in BB-FET compared with in CB-ET (9.0% vs. 2.3%, adjusted odds ratio [OR] and 95% confidence interval [CI], 4.85 [1.34, 17.56]). In twins, the birthweight (median [range], 2.70 kg [1.55-3.60 kg] vs. 2.50 kg [1.23-3.75 kg]) was higher in BB-FET than in CB-ET and the gestational age was longer in BB-FET than in CB-ET (median [range], 36.71 weeks [31.14-39.29 weeks] vs. 35.57 weeks [30.57-38.43 weeks]). There was no difference in the incidence of singleton births between the two groups except in the incidence of preterm births (28-37 weeks; 5.3% vs. 16.5% in CB-ET and BB-FET). No significant differences were detected in the incidence of perinatal deaths, birth defects, gender of neonates, and large for gestational age in both singletons and twins, although the numbers of some events were small. BB-FET is associated with a higher incidence of gestational hypertension but better neonatal outcomes compared with CB-ET, especially in twins. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling.
Full Text Available In the current context of food security, increase of plant protein production in a sustainable manner represents one of the major challenges of agronomic research, which could be partially resolved by increased cultivation of legume crops. Medicago truncatula is now a well-established model for legume genomic and genetic studies. With the establishment of genomics tools and mutant populations in M. truncatula, it has become an important resource to answer some of the basic biological questions related to plant development and stress tolerance. This review has an objective to overview a decade of genetic studies in this model plant from generation of mutant populations to nowadays. To date, the three biological fields, which have been extensively studied in M. truncatula, are the symbiotic nitrogen fixation, the seed development, and the abiotic stress tolerance, due to their significant agronomic impacts. In this review, we summarize functional genetic studies related to these three major biological fields. We integrated analyses of a nearly exhaustive list of genes into their biological contexts in order to provide an overview of the forefront research advances in this important legume model plant.
Jamieson, Annie; Radick, Gregory
Twenty-first-century biology rejects genetic determinism, yet an exaggerated view of the power of genes in the making of bodies and minds remains a problem. What accounts for such tenacity? This article reports an exploratory study suggesting that the common reliance on Mendelian examples and concepts at the start of teaching in basic genetics is…
Full Text Available Background: Inborn metabolic disorders (IMDs form a large group of rare, but often serious, metabolic disorders. Aims: Our objective was to construct a decision tree, based on classification algorithm for the data on three metabolic disorders, enabling us to take decisions on the screening and clinical diagnosis of a patient. Settings and Design: A non-incremental concept learning classification algorithm was applied to a set of patient data and the procedure followed to obtain a decision on a patient’s disorder. Materials and Methods: Initially a training set containing 13 cases was investigated for three inborn errors of metabolism. Results: A total of thirty test cases were investigated for the three inborn errors of metabolism. The program identified 10 cases with galactosemia, another 10 cases with fructosemia and the remaining 10 with propionic acidemia. The program successfully identified all the 30 cases. Conclusions: This kind of decision support systems can help the healthcare delivery personnel immensely for early screening of IMDs.
Herlihy, Amy Simone
Klinefelter Syndrome (KS) is a genetic condition (47,XXY) affecting males and resulting in a spectrum of clinical features, ranging from azoospermia, small testes, breast development, testosterone deficiency, and decreased body and facial hair to varying levels of cognitive, social, behavioural and learning difficulties. The phenotype can be highly variable between individuals, and genetic factors such as functionality of the androgen receptor have been postulated to play a role. The pre...
Fahimzad, Alireza; Afgeh, Seyyed Abolfazl; Eghbali, Elham; Abdinia, Babak; Shiva, Farideh; Rahbar, Mohammad
Cytomegalovirus (CMV) is a leading cause of congenital infection in neonates. Most infants with congenital CMV infection are asymptomatic at birth and not diagnosed on routine clinical examination. To identify these at-risk infants early in life, polymerase chain reaction (PCR) assays are done to screen large populations of newborn infants. We carried out a pilot study to estimate the prevalence of CMV in saliva from newborns by DNA PCR assay. This study was performed from January 2012 to March 2012 at a maternity hospital in the south of Tehran. All newborns aged between 1 to 14 days born at this hospital were enrolled. Saliva specimens from newborns were collected by swabbing the inside of the baby's mouth and stored at -70 degrees C until PCR processing for virus detection. Six-hundred and twenty infants between 1 to 14 days of age were enrolled during the study period of two months. The PCR assay was positive for CMV in 2 newborns [0.3%]. Both of these infants were asymptomatic for congenital CMV at birth and also when followed up at three months and six months of age. Our findings reveal that because of a low yield of positive results, screening for congenital CMV infection would not be cost-effective in Iranian neonates.
Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Kalager, Mette; Zahl, Per-Henrik
Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Cohort study. Denmark from 1980 to 2010. Women aged 35 to 84 years. Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times. Trends in the incidence of advanced (>20 mm) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing the incidence for nonadvanced tumors among women aged 35 to 49, 50 to 69, and 70 to 84 years in screening and nonscreening areas. Screening was not associated with lower incidence of advanced tumors. The incidence of nonadvanced tumors increased in the screening versus prescreening periods (incidence rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted for regional differences in women younger than the screening age, found that 711 invasive tumors and 180 cases of DCIS were overdiagnosed in 2010 (overdiagnosis rate of 48.3% [including DCIS] and 38.6% [excluding DCIS]). Regional differences complicate interpretation. Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%). None.
Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous
Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.
Zhang, Wen-Jing; Zhang, Yong-Qing; Yuan, Qing-Jun; Huang, Lu-Qi; Jiang, Dan; Jing, Li
The author introduces the basic concepts of microsatellite and population genetics and its characteristics, expounds the application of these theories for population genetic structure and genetic diversity, gene flow and evolutionary significant unit ESU division research. This paper discuss its applicationin study of genetic causes, origin of cultivation, different regional origins of geoherbs, aiming at providing a new theory and method for geoherbs.
del Giacco Stefano
Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is
Tsai, Chia-Ti; Hsieh, Chia-Shan; Chang, Sheng-Nan; Chuang, Eric Y.; Ueng, Kwo-Chang; Tsai, Chin-Feng; Lin, Tsung-Hsien; Wu, Cho-Kai; Lee, Jen-Kuang; Lin, Lian-Yu; Wang, Yi-Chih; Yu, Chih-Chieh; Lai, Ling-Ping; Tseng, Chuen-Den; Hwang, Juey-Jen; Chiang, Fu-Tien; Lin, Jiunn-Lee
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10−24). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway. PMID:26831368
雷彩霞; 张月萍; 孙晓溪
植入前遗传学诊断/筛查(PGD/PGS)技术发展多年,其指征始终存在争议.PGD指征较为明确,单基因遗传病、染色体异常人群、人类白细胞抗原(HLA)配型为其适用人群.PGS的指征争议较多,主要面向反复流产、反复植入失败、高龄人群,目的是提高妊娠率及活产率.然而第一代PGS技术[PGS#1,卵裂球活检及荧光原位杂交(FISH)-PGS]技术未显示明显效果,甚至降低了妊娠率及活产率.第二代PGS技术(PGS2.0)增加了严重男性因素不育为指征,其核心为囊胚活检及全染色体筛查(CCS),对上述人群的临床效果较为明显,降低了流产风险并提高了成功率及活产率.PGS2.0已极大地改变了辅助生殖技术(ART)面貌,可能成为未来生殖中心对所有患者的一个常规项目.目前仍然需要多中心前瞻性随机病例对照研究重新评估PGS.%Controversies in indications of preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) are developing with the rapid improvement of the technology for years.PGD is clearly indicated for monogenetic diseases,chromosome abnormalities and HLA typing,while PGS is ambiguous in indications,with the purpose to improve fertility rate and take-home baby rate for patients suffered from recurrent spontaneous abortion (RSA),recurrent implantation failure and advanced maternal age.However,the first generation PGS technology [PGS#1,biopsy of blastomere plus fluorescent in situ hybridization (FISH)-PGS] has failed to provide promising clinical effect,and to the contrary decreased the fertility and take-home baby rate.The second generation PGS technology (PGS2.0),which is focused on biopsy ofblastocyst plus comprehensive chromosome screening (CCS) and adds severe male infertility factor as an indicator,has shown promising clinical effect of decreased abortion rate and increased fertility and take-home baby rate.PGS2.0 has dramatically changed features of assisted reproductive
Laura J James
Full Text Available Prostate cancer is the most commonly diagnosed non-skin cancer in men. Screening for prostate cancer is widely accepted; however concerns regarding the harms outweighing the benefits of screening exist. Although patient's play a pivotal role in the decision making process, men may not be aware of the controversies regarding prostate cancer screening. Therefore we aimed to describe men's attitudes, beliefs and experiences of prostate cancer screening.Systematic review and thematic synthesis of qualitative studies on men's perspectives of prostate cancer screening. Electronic databases and reference lists were searched to October 2016.Sixty studies involving 3,029 men aged from 18-89 years, who had been screened for prostate cancer by Prostate Specific Antigen (PSA or Digital Rectal Examination (DRE and not screened, across eight countries were included. Five themes were identified: Social prompting (trusting professional opinion, motivation from family and friends, proximity and prominence of cancer; gaining decisional confidence (overcoming fears, survival imperative, peace of mind, mental preparation, prioritising wellbeing; preserving masculinity (bodily invasion, losing sexuality, threatening manhood, medical avoidance; avoiding the unknown and uncertainties (taboo of cancer-related death, lacking tangible cause, physiological and symptomatic obscurity, ambiguity of the procedure, confusing controversies; and prohibitive costs.Men are willing to participate in prostate cancer screening to prevent cancer and gain reassurance about their health, particularly when supported or prompted by their social networks or healthcare providers. However, to do so they needed to mentally overcome fears of losing their masculinity and accept the intrusiveness of screening, the ambiguities about the necessity and the potential for substantial costs. Addressing the concerns and priorities of men may facilitate informed decisions about prostate cancer screening
O Dea, Angela
The risks associated with gestational diabetes mellitus (GDM) are well recognized, and there is increasing evidence to support treatment of the condition. However, clear guidance on the ideal approach to screening for GDM is lacking. Professional groups continue to debate whether selective screening (based on risk factors) or universal screening is the most appropriate approach. Additionally, there is ongoing debate about what levels of glucose abnormalities during pregnancy respond best to treatment and which maternal and neonatal outcomes benefit most from treatment. Furthermore, the implications of possible screening options on health care costs are not well established. In response to this uncertainty there have been repeated calls for well-designed, randomised trials to determine the efficacy of screening, diagnosis, and management plans for GDM. We describe a randomised controlled trial to investigate screening uptake rates and the clinical and cost effectiveness of screening in primary versus secondary care settings. The objective of this study is to assess screening uptake rates, and the clinical and cost effectiveness of screening for GDM in primary versus secondary care.
Smoller Jordan W
Full Text Available Abstract Background One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder. Methods and design We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD. The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach. Discussion Identification of
Driver, John P; Chen, Yi-Guang; Mathews, Clayton E
Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.
Full Text Available Apart from the well-known role of somatic cell count as a parameter reflecting the inflammatory status of the mammary gland, the composition of cells isolated from milk is considered as a valuable material for gene expression studies in mammals. Due to its unique composition, in recent years an increasing interest in mare's milk consumption has been observed. Thus, investigating the genetic background of horse's milk variability presents and interesting study model. Relying on 39 milk samples collected from mares representing three breeds (Polish Primitive Horse, Polish Cold-blooded Horse, Polish Warmblood Horse we aimed to investigate the utility of equine milk somatic cells as a source of mRNA and to screen the best reference genes for RT-qPCR using geNorm and NormFinder algorithms. The results showed that despite relatively low somatic cell counts in mare's milk, the amount and the quality of the extracted RNA are sufficient for gene expression studies. The analysis of the utility of 7 potential reference genes for RT-qPCR experiments for the normalization of equine milk somatic cells revealed some differences between the outcomes of the applied algorithms, although in both cases the KRT8 and TOP2B genes were pointed as the most stable. Analysis by geNorm showed that the combination of 4 reference genes (ACTB, GAPDH, TOP2B and KRT8 is required for apropriate RT-qPCR experiments normalization, whereas NormFinder algorithm pointed the combination of KRT8 and RPS9 genes as the most suitable. The trial study of the relative transcript abundance of the beta-casein gene with the use of various types and numbers of internal control genes confirmed once again that the selection of proper reference gene combinations is crucial for the final results of each real-time PCR experiment.
Nathaniel D Maynard
Full Text Available Latently infecting viruses are an important class of virus that plays a key role in viral evolution and human health. Here we report a genome-scale forward-genetics screen for host-dependencies of the latently-infecting bacteriophage lambda. This screen identified 57 Escherichia coli (E. coli genes--over half of which have not been previously associated with infection--that when knocked out inhibited lambda phage's ability to replicate. Our results demonstrate a highly integrated network between lambda and its host, in striking contrast to the results from a similar screen using the lytic-only infecting T7 virus. We then measured the growth of E. coli under normal and infected conditions, using wild-type and knockout strains deficient in one of the identified host genes, and found that genes from the same pathway often exhibited similar growth dynamics. This observation, combined with further computational and experimental analysis, led us to identify a previously unannotated gene, yneJ, as a novel regulator of lamB gene expression. A surprising result of this work was the identification of two highly conserved pathways involved in tRNA thiolation-one pathway is required for efficient lambda replication, while the other has anti-viral properties inhibiting lambda replication. Based on our data, it appears that 2-thiouridine modification of tRNAGlu, tRNAGln, and tRNALys is particularly important for the efficient production of infectious lambda phage particles.
Full Text Available Most genetic epidemiological study designs fall into one of two categories: family-based and population-based (case-control. However, recent advances in statistical genetics call for study designs that combine these two approaches. We describe the household contact study design as we have applied it in our several years of study of the epidemiology of tuberculosis. Though we highlight its applicability for genetic epidemiological studies of infectious diseases, there are many facets of this design that are appealing for modern genetic studies, including the simultaneous enrollment of related and unrelated individuals, closely and distantly related individuals, collection of extensive epidemiologic and phenotypic data, and evaluation of effects of shared environment and gene by environment interaction. These study design characteristics are particularly appealing for current sequencing studies.
Kaufmann, J. O.; Krapels, I. P. C.; Van Brussel, B. T. J.; Zekveld-Vroon, R. C.; Oosterwijk, J. C.; van Erp, F.; van Echtelt, J.; Zwijnenburg, P. J. G.; Petrij, F.; Bakker, E.; Giordano, P. C.
OBJECTIVE: Universal newborn screening for hemoglobinopathies started in The Netherlands in 2007. Herewith severe conditions, such as sickle cell disease, β-thalassemia major and hemoglobin H disease are putatively identified. Additionally, at least 1,800 carriers of hemoglobin variants associated
Staunstrup, Nicklas Heine; Sharma, Nynne; Bak, Rasmus Otkjær
Analogues of vitamin D3 are extensively used in the treatment of various illnesses, such as osteoporosis, inflammatory skin diseases, and cancer. Functional testing of new vitamin D3 analogues and formulations for improved systemic and topical administration is supported by sensitive screening me...
Tohno, Eriko; Umemoto, Takeshi; Sasaki, Kyoko; Morishima, Isamu; Ueno, Ei
Purpose: To determine whether adding screening ultrasonography to screening mammography can reduce patient recall rates and increase cancer detection rates. Materials and methods: We analyzed the results of mammography and ultrasonography breast screenings performed at the Total Health Evaluation Center Tsukuba, Japan, between April 2011 and March 2012. We also reviewed the modalities and results of diagnostic examinations from women with mammographic abnormalities who visited the Tsukuba Medical Center Hospital for further testing. Results: Of 11,753 women screened, cancer was diagnosed in 10 (0.22%) of the 4529 participants who underwent mammography alone, 23 (0.37%) of the 6250 participants who underwent ultrasonography alone, and 5 (0.51%) of the 974 participants who underwent mammography and ultrasonography. The recall rate due to mammographic abnormalities was 4.9% for women screened only with mammography and 2.6% for those screened with both modalities. The cancer detection rate was 0.22% for women screened only with mammography (positive predictive value, 4.5%) and 0.31% for those screened with both modalities (positive predictive value, 12.0%). Of the 211 lesions presenting as mammographic abnormalities investigated further, diagnostic ultrasonography found no abnormalities in 63 (29.9%) and benign findings in 69 (33.7%). The rest 36.4% needed mammography, cytological or histological examinations or follow-up in addition to diagnostic ultrasonography. Conclusions: It is possible to reduce the recall rate in screening mammography by combining mammography and ultrasonography for breast screening
Leung, Doris Y P; Chen, Joanne M T; Lou, Vivian W Q; Wong, Eliza M L; Chan, Aileen W K; So, Winnie K W; Chan, Carmen W H
Colorectal cancer (CRC) screening is a cost-effective prevention and control strategy. However, the promotion of CRC screening for older adults may be difficult because reading CRC prevention information may evoke embarrassment, fear, and anxiety towards the screening procedure and cancer diagnosis. This study aims to (1) examine the effects of three promotional materials for CRC screening on the attitudes toward CRC screening tests (screening interest, screening effectiveness, and trust in the screening results) and cancer fear, and (2) to explore the interaction effect of cancer fear with screening effectiveness and trust in the screening results on screening interest of the three screening tests (fecal occult blood test (FOBT), flexible sigmoidoscopy, and colonoscopy) among Chinese older adults. A total of 114 community-dwelling older adults were asked to look at the corresponding promotional materials (pamphlet, cartoon, and video) of one of the three study groups. The pamphlet and video represent convention strategies and the cartoon represents an innovative strategy. No significant difference was observed in the screening interest and cancer fear across groups. FOBT was the most preferred screening modality. The video group has a large proportion agreed screening effectiveness of flexible sigmoidoscopy than pamphlet and cartoon groups and trusted in the screening results for FOBT and flexible sigmoidoscopy than the pamphlet group. Logistic regression results showed that the effect of trust in the screening results on screening interest for colonoscopy was greater among participants with higher cancer fear than those with lower cancer fear level. In conclusion, the three promotional groups had produced similar results in their attitudes toward CRC screening and cancer fear. The use of cartoons may be a comparable approach with conventional methods in the promotion of CRC screening. Additional components that can arouse fear and boost response efficacy
Full Text Available BACKGROUND Cervical and breast cancers are the common malignancies among female population in India. Though there are approved screening methods available to prevent and detect these cancers at an early stage, there is a lack of awareness about cancer screening among general public as well as the health care professionals. This study is aimed to identify the knowledge, attitude and practice (KAP among the nursing staff regarding cancer screening in these two diseases. METHOD A cross-sectional interview based survey was conducted among 303 female nursing staff working in a government medical college hospital from November 2015 to December 2015. Ethical committee approval was taken. Verbal informed consent was sought from the study subjects. Nursing staff who gave consent to participate in the study were enrolled. There were no specific inclusion or exclusion criteria for the study subjects. A structured pretested questionnaire regarding knowledge, attitude and practice (KAP was used to collect the data. The questions were open-ended. Recall and recognition type of questions were used. The data was entered into MS Excel worksheet and analysed using descriptive statistics. RESULTS Total of 303 nurses included in the study. The age ranged from 21 to 64 years. Median age is 38 years. Only 24.4% (74/303 of Nurses were aware of cancer screening and many of them were aware of Pap smear (55.1%, 167/303 and mammogram (66.3%, 201/303 as investigational tools in diagnosing cancer. Only 17 out of 303 (5.6% nurses had Pap smear test done with an average of 1.23% Pap smear per individual. Mammogram screening was done in 13% (15/115 of the eligible nurses with an average of 1.2% mammogram per individual. The most common reason for not undergoing screening as expressed was they did not feel the need to be screened unless they were symptomatic (55%, they are too young for screening (14.8%, shyness (11.1%, fear (11.1% and lack of time (7.4%. However, 90% of them
Freeman, Elaine; Howell-Jones, Rebecca; Oliver, Isabel; Randall, Sarah; Ford-Young, William; Beckwith, Philippa; McNulty, Cliodna
General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP), have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. The NCSP should consider developing a range of more discrete but eye
Freeman, Elaine; Howell-Jones, Rebecca; Oliver, Isabel; Randall, Sarah; Ford-Young, William; Beckwith, Philippa; McNulty, Cliodna
Background General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP), have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Methods Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Results Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. Conclusion The NCSP should consider developing
Full Text Available Abstract Background General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP, have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Methods Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Results Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. Conclusion The NCSP
Full Text Available First international conference on composites, biocomposites and nanocomposites, DUT, Durban, South Africa, 2-4 December 2013 SCREENING LIFE CYCLE ASSESSMENT STUDY OFA SISAL FIBRE REINFORCED MICRO-CONCRETE STRUCTURAL INSULATED PANEL Naa Lamkai Ampofo...
Li, H., E-mail: firstname.lastname@example.org [Department of Precision Instrument, Tsinghua University, Beijing, 100084 (China); Gillen, R. [Institut für Festkörperphysik. Technische Universität Berlin. Hardenbergstr. 36, 10623 Berlin (Germany); Robertson, J., E-mail: email@example.com [Engineering Department, University of Cambridge, Cambridge CB2 1PZ (United Kingdom)
The screened exchange (sX) hybrid functional has been widely used in computational material science. Although it has widely been studied in bulk systems, less is known about its functional behavior in surface systems which are crucial to many technologies such as materials synthesis and nano-electronic devices. Assessing the screening dependent functional behaviors in the surface systems is therefore important for its application in such systems. In this work, we investigate the screening effects of the sX in CO adsorption on Pt(111) surface. The differences between the sX and Heyd-Scuseria-Ernzerhof (HSE06) hybrid functionals, and the effects of screening parameters are studied. The screening has two effects: first, the HOMO-LUMO gap is screening dependent. This affects the site preference most significantly. In this work, atop adsorption of CO/Pt(111) is predicted by the hybrid functionals with screened exchange potential. The sX(1.44) gives the largest HOMO-LUMO gap for the isolated CO molecule. The adsorption energy difference between the atop and fcc site is also the largest by the sX(1.44) which is explained by the reduced metal d states to the CO 2π* state back-donation, with stronger effect for the fcc adsorption than for the atop adsorption; second, the adsorption energy is screening dependent. This can be seen by comparing the sX(2.38) and HSE06 which have different screening strengths. They show similar surface band structures for the CO adsorption but different adsorption energies, which is explained by the stronger CO 5σ state to the metal d states donation or the effectively screened Pauli repulsion. This work underlines the screening strength as a main difference between sX and HSE06, as well as an important hybrid functional parameter for surface calculation.
Pignone Michael P
Full Text Available Abstract Background An estimated one-half of Americans have limited health literacy skills. Low literacy has been associated with less receipt of preventive services, but its impact on colorectal cancer (CRC screening is unclear. We sought to determine whether low literacy affects patients' knowledge or receipt of CRC screening. Methods Pilot survey study of patients aged 50 years and older at a large, university-affiliated internal medicine practice. We assessed patients' knowledge and receipt of CRC screening, basic sociodemographic information, and health literacy level. We defined limited literacy as reading below the ninth grade level as determined by the Rapid Estimate of Adult Literacy in Medicine. Bivariate analyses and exact logistic regression were used to determine the association of limited health literacy with knowledge and receipt of CRC screening. Results We approached 105 patients to yield our target sample of 50 completing the survey (recruitment rate 48%. Most subjects were female (72%, African-American (58%, and had household incomes less than $25,000 (87%. Overall, 48% of patients had limited literacy skills (95% CI 35% to 61%. Limited literacy patients were less likely than adequate literacy patients to be able to name or describe any CRC screening test (50% vs. 96%, p Conclusion Patients with limited literacy skills are less likely to be knowledgeable of CRC screening compared to adequate literacy patients. Primary care providers should ensure patients' understanding of CRC screening when discussing screening options. Further research is needed to determine if educating low literacy patients about CRC screening can increase screening rates.
Gendarme, S; Perrot, É; Reskot, F; Bhoowabul, V; Fourre, G; Souquet, P-J; Milleron, B; Couraud, S
The National Lung Screening Trial found that, in a selected population with a high risk of lung cancer, an annual low-dose CT-scan decreased lung cancer mortality by 20% and overall mortality by 7% compared to annual chest X-Ray. In France, a work group stated that individual screening should be considered in this setting. However, the economic impact of an organized and generalized (to all eligible individuals) screening in France was never reported. This is a modeling study using French population demographic data and published data from randomized screening trials. We used the same selection criteria as NLST: 55-74-year-old smokers for at least 30 pack-years, current smoker or quit less than 15 years. We computed a second model including also 50-54-year-old individuals. Then, we used different participation rates: 65%, 45%, and 32%. According to the considered model, there would be 1,650,588 to 2,283,993 subjects eligible to screening in France. According to the model and participation rate, lung cancer screening would diagnose 3600 to 10,118 stages 1/2 lung cancer each year. There would be 5991 to 16,839 false-positives, of whom 1416 to 3981 would undergo unnecessary surgery. Screening policy would cost 105 to 215 € million per year. However, increasing the price of a cigarette pack by 0.05 to 0.10 € would fully cover the screening costs. Participation rate is a key point for screening impact. Screening could be easily funded by a small increase in cigarette prices. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Full Text Available Recent report of WHO shows 113000 children in India succumb to death due to Rotavirus diarrhea. Lack of knowledge about pathogenesis of virus has led to lack of therapy for severely infected patients. Previous studies have found that, animal rotavirus requires sialyl glycan moieties on cell surface for pathogenesis. Present study states that human rotaviruses also follows same path and this specificity of virus leads to host genetic predisposition for the infection as well as the disease. Two hundred children less than 5 years of age clinically suspected of viral diarrhea were screened for rotavirus infection. EDTA blood was processed for analyzing DNA sequences of various fucosyltransferase genes. Lewis antigens which are secretory form of ABO Histo Blood Group Antigens were correlated with the genotype of patient. Genetics of HBGA secretion, particularly, basis of Leb expression manifested by fucosyltransferase-2 enzyme was studied in healthy individuals and was compared in cases of rotavirus positive and negative diarrhea. Positive clinical isolates with various genotypes were purified from stool samples and gene for VP4 - surface spike protein was sequenced. Using Bioinformatics interphase, three dimensional protein structures were modeled and their functional domains were analyzed. All these modeled proteins were docked with Leb HBGA (Lewis-b Histo Blood Group Antigens using molecular docking software. In present study, to investigate possible association of the rotavirus with host genome, we screened highly suspected genes involved in expression of glycoproteins on enterocytes. This study performed for prevalent Indian strains of rotaviruses provides possible evidence that, VP8 domain of VP4 spike protein utilizes Leb surface antigen for attachment and entry to enterocytes in the intestine. The FUT2 and FUT3 gene has been found to show significant association with the rotavirus infection hence can serve as a biomarker for genetic
Dibosa-Osadolor, Onome; Roberts, Tracy
The aim of this study was to review, systematically and critically, evidence used to derive estimates of cost-effectiveness of human immunodeficiency virus (HIV) screening. A systematic review was conducted. Searched were three main electronic bibliographic databases from 1993 to 2008 using key words including HIV, mass screening, HAART, economic evaluation, cost-effectiveness analysis, modeling. We included studies of sexually transmitted HIV infection in both sexes, including studies comparing diagnostic testing protocols and partner notification. Outcomes included were cases of HIV infection detected, deterioration to the AIDS state, secondary transmission of HIV, the quality-adjusted life-years/survival, costs, and cost-effectiveness of HIV screening. Eighty-four papers were identified; ten of which were formal economic evaluations, one cost study, three effectiveness studies, and three systematic reviews of HIV prevention programs. The predominant assertion was that HIV screening is cost-effective; methodological problems, such as the preponderance of static models which are inappropriate for infectious diseases, varying perspectives from which the studies were analyzed, and arbitrary threshold incremental cost-effectiveness ratio levels, limited the validity of these findings, and their usefulness in informing health policy decisions. The majority of published economic evaluations are based on inappropriate static models. This flaw renders the results of these studies as inconclusive and the purported cost-effectiveness of HIV screening debatable. The results of this review could form a basis for consideration of further research and analysis by health economists into the cost-effectiveness of HIV screening.
Bertola Débora Romeo
Full Text Available Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71%; craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87%; cardiac anomalies (65%, and fetal pads in fingers and toes (70%. After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic.
Ingebrigtsen, Truls S; Thomsen, Simon F; van der Sluis, Sophie
Heritability of forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), and peak expiratory flow (PEF) has not been previously addressed in large twin studies. We evaluated the genetic contribution to individual differences observed in FEV(1), FVC, and PEF using data from...... the largest population-based twin study on spirometry. Specially trained lay interviewers with previous experience in spirometric measurements tested 4,314 Danish twins (individuals), 46-68 years of age, in their homes using a hand-held spirometer, and their flow-volume curves were evaluated. Modern variance...
Wilfond, Benjamin S; Kauffman, Tia L; Jarvik, Gail P; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Gilmore, Marian; Himes, Patricia; Kraft, Stephanie A; Porter, Kathryn M; Schneider, Jennifer L; Punj, Sumit; Leo, Michael C; Dickerson, John F; Lynch, Frances L; Clarke, Elizabeth; Rope, Alan F; Lutz, Kevin; Goddard, Katrina A B
Genomics-based carrier screening is one of many opportunities to use genomic information to inform medical decision making, but clinicians, health care delivery systems, and payers need to determine whether to offer screening and how to do so in an efficient, ethical way. To shed light on this issue, we conducted a study in the period 2014-17 to inform the design of clinical screening programs and guide further health services research. Many of our results have been published elsewhere; this article summarizes the lessons we learned from that study and offers policy insights. Our experience can inform understanding of the potential impact of expanded carrier screening services on health system workflows and workforces-impacts that depend on the details of the screening approach. We found limited patient or health system harms from expanded screening. We also found that some patients valued the information they learned from the process. Future policy discussions should consider the value of offering such expanded carrier screening in health delivery systems with limited resources.
Jung Hyun Lee, MPH
Full Text Available Summary: Purpose: The purpose of this study was to evaluate the contributions and limitations of the cervical cancer screening test with accuracy in Korea. Methods: This was a retrospective observational study. The study population consisted of all participants who underwent cervical cancer screening test from 2009 to 2014. The data were obtained from National Health Information Database (NHID which represents medical use records of most Koreans. As the indices for contributions and limitations of the screening test, crude detection rate, incidence rate of interval cancer, sensitivity, specificity, and positive predictive value were used. Results: The crude detection rate of screening test per 100,000 participants increased from 100.7 in 2009 to 102.1 in 2014. The incidence rate of interval cancer per 100,000 negatives decreased from 13.0 in 2009 to 10.2 in 2014. The sensitivities of screening test were 88.7% in 2009 and 91.2% in 2014, and the specificities were 98.5% in 2009 and 97.7% in 2014. The positive predictive value of screening decreased from 6.2% in 2009 to 4.3% in 2014. Conclusion: The Korean national cervical cancer screening program has improved in accuracy and has contributed to detection of early stage of cervical cancer over the years. Along with efforts to promote participation in cancer screening programs, quality control over the screening program should be enhanced. Keywords: carcinoma in situ, early detection of cancer, Papanicolaou test, sensitivity and specificity, uterine cervical neoplasms
Ndejjo, Rawlance; Mukama, Trasias; Kiguli, Juliet; Musoke, David
To explore community knowledge, facilitators and barriers to cervical cancer screening among women in rural Uganda so as to generate data to inform interventions. A qualitative study using focus group discussions and key informant interviews. Discussions and interviews carried out in the community within two districts in Eastern Uganda. Ten ( 10) focus group discussions with 119 screening-eligible women aged between 25 and 49 years and 11 key informant interviews with healthcare providers and administrators. Study participants' knowledge about cervical cancer causes, signs and symptoms, testing methods and prevention was poor. Many participants attributed the cause of cervical cancer to use of contraception while key informants said that some believed it was due to witchcraft. Perceptions towards cervical cancer and screening were majorly positive with many participants stating that they were at risk of getting cervical cancer. The facilitators to accessing cervical cancer screening were: experiencing signs and symptoms of cervical cancer, family history of the disease and awareness of the disease/screening service. Lack of knowledge about cervical cancer and screening, health system challenges, fear of test outcome and consequences and financial constraints were barriers to cervical cancer screening. Whereas perceptions towards cervical cancer and screening were positive, knowledge of study participants on cervical cancer was poor. To improve cervical cancer screening, effort should be focused on reducing identified barriers and enhancing facilitators. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Levels of Evidence for Cancer Genetics Studies addresses the process and challenges of developing evidence-based summaries. Get information about how to weigh the strength of the evidence from cancer genetics studies in this summary for clinicians.
Brezina, Paul R; Kutteh, William H
Genetic diagnostic technologies are rapidly changing the way medicine is practiced. Preimplantation genetic testing is a well established application of genetic testing within the context of in vitro fertilization cycles. It involves obtaining a cell(s) from a developing embryo in culture, which is then subjected to genetic diagnostic analysis; the resulting information is used to guide which embryos are transferred into the uterus. The potential applications and use of this technology have increased in recent years. Experts agree that preimplantation genetic diagnosis is clinically appropriate for many known genetic disorders. However, some applications of such testing, such as preimplantation genetic screening for aneuploidy, remain controversial. Clinical data suggest that preimplantation genetic screening may be useful, but further studies are needed to quantify the size of the effect and who would benefit most. © BMJ Publishing Group Ltd 2015.
Dietrich, Andrea; Fernandez, Thomas V; King, Robert A; State, Matthew W; Tischfield, Jay A; Hoekstra, Pieter J; Heiman, Gary A
Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarified fully. There is now mounting evidence that the genetic risks for TS include both common and rare variants and may involve complex multigenic inheritance or, in rare cases, a single major gene. Based on recent progress in many other common disorders with apparently similar genetic architectures, it is clear that large patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent-child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA) are part of a sharing repository located within the National Institute for Mental Health Center for Collaborative Genomics Research on Mental Disorders, USA, and will be made available to the broad scientific community. This resource will ultimately facilitate better understanding of the pathophysiology of TS and related disorders and the development of novel therapies. Here, we describe the objectives and methods of the TIC Genetics study as a reference for future studies from our group and to facilitate collaboration between genetics consortia in the field of TS.
Zahl, Per-Henrik; Gøtzsche, Peter C; Mæhlen, Jan
The natural history of screen-detected breast cancers is not well understood. A previous analysis of the incidence change during the introduction of the Norwegian screening programme in the late 1990s suggested that the natural history of many screen-detected invasive breast cancers is to regress...... spontaneously but the study was possibly confounded by use of hormone replacement therapy in the population. We did a similar analysis of data collected during an earlier period when few women were exposed to hormone replacement therapy....
Scholtens-Toma, I.M.J.; Laurensse, E.; Molenaar, B.; Zaaijer, S.; Gaballo, H.M.S.; Boleij, P.A.; Bak, A.; Kok, E.J.
Nowadays most animal feed products imported into Europe have a GMO (genetically modified organism) label. This means that they contain European Union (EU)-authorized GMOs. For enforcement of these labeling requirements, it is necessary, with the rising number of EU-authorized GMOs, to perform an
VanDenHeuvel, A; Fitzgerald, M; Greiner, B; Perry, I J
The objectives of this study were to assess the feasibility of administering the CHecklist for Autism in Toddlers (CHAT) at the 18-month developmental check, estimate the prevalence of screening positive for autism at the first and second administrations of the CHAT and estimate the prevalence of diagnosed cases of autism. A cross-sectional study design was utilised and data was collected at child developmental screening clinics in counties Cork and Kerry. The sample group consisted of infants attending the routine 18-month developmental assessment, who were broadly representative of infants in the catchment area. The main outcome measure was a medium or high-risk score following two administrations of the CHAT screening instrument and a positive diagnosis of autism after clinical assessment. The CHAT was administered to 2117 infants (79% of those approached) of whom 29 were scored at medium or high risk at first screening, resulting in a prevalence rate of 137 per 10,000 (95% CI: 87-187). A total of 7 of the 29 first screen positive infants were positive (medium or high risk) at second screening, 12 were low risk and 10 parents refused to participate. On subsequent clinical assessment of the 7 infants screening positive on first and second assessment and assessment of 5 of the 10 infants whose parents declined second screening, 7 children received a diagnosis of autism. Thus the overall prevalence of clinically diagnosed autism following this screening exercise was 33.1 per 10,000 (95% CI: 13.3 to 68.0). The CHAT instrument is a useful tool to help identify childhood autism among infants. Routine use of this instrument at 18-month developmental assessment merits consideration.
Yeniçerioğlu, Yavuz; Akdam, Hakan; Dursun, Belda; Alp, Alper; Sağlam Eyiler, Funda; Akın, Davut; Gün, Yelda; Hüddam, Bülent; Batmazoğlu, Mehmet; Gibyeli Genek, Dilek; Pirinççi, Serhat; Ersoy, İsmail Rıfkı; Üzüm, Atilla; Soypaçacı, Zeki; Tanrısev, Mehmet; Çolak, Hülya; Demiral Sezer, Sibel; Bozkurt, Gökay; Akyıldız, Utku Oğan; Akyüz Ünsal, Ayşe İpek; Ünübol, Mustafa; Uslu, Meltem; Eryılmaz, Ufuk; Günel, Ceren; Meteoğlu, İbrahim; Yavaşoğlu, İrfan; Ünsal, Alparslan; Akar, Harun; Okyay, Pınar
Fabry's disease is an X-linked inherited, rare, progressive, lysosomal storage disorder, affecting multiple organs due to the deficient activity of α-galactosidase A (α-Gal A) enzyme. The prevalence has been reported to be 0.15-1% in hemodialysis patients; however, the information on the prevalence in chronic kidney disease not on dialysis is lacking. This study aimed to determine the prevalence of Fabry's disease in chronic kidney disease. The patients older than 18 years, enclosing KDIGO 2012 chronic kidney disease definitions, not on dialysis, were enrolled. Dried blood spots on Guthrie papers were used to analyze α-Gal A enzyme and genetic analysis was performed in individuals with enzyme activity ≤1.2 μmol/L/h. A total of 1453 chronic kidney disease patients not on dialysis from seven clinics in Turkey were screened. The mean age of the study population was 59.3 ± 15.9 years. 45.6% of patients were female. The creatinine clearance of 77.3% of patients was below 60 mL/min/1.73 m 2 , 8.4% had proteinuria, and 2.5% had isolated microscopic hematuria. The mean value of patients' α-Gal A enzyme was detected as 2.93 ± 1.92 μmol/L/h. 152 patients had low levels of α-Gal A enzyme activity (≤1.2 μmol/L/h). In mutation analysis, A143T and D313Y variants were disclosed in three male patients. The prevalence of Fabry's disease in chronic kidney disease not on dialysis was found to be 0.2% (0.4% in male, 0.0% in female). Fabry's disease should be considered in the differential diagnosis of chronic kidney disease with unknown etiology even in the absence of symptoms and signs suggestive of Fabry's disease.
Full Text Available Excess lipid storage is an epidemic problem in human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications is of great interest. Here we screened >320.000 compounds for their ability to prevent a cellular lipid accumulation phenotype. We used fly cells because the multifarious tools available for this organism should facilitate unraveling the mechanism-of-action of active small molecules. Of the several hundred lipid storage inhibitors identified in the primary screen we concentrated on three structurally diverse and potent compound classes active in cells of multiple species (including human and negligible cytotoxicity. Together with Drosophila in vivo epistasis experiments, RNA-Seq expression profiles suggested that the target of one of the small molecules was diacylglycerol acyltransferase 1 (DGAT1, a key enzyme in the production of triacylglycerols and prominent human drug target. We confirmed this prediction by biochemical and enzymatic activity tests.
Background Oral cancer is increasing in incidence in the UK and indeed worldwide. Delay in diagnosis is common; up to half of patients are diagnosed with advanced lesions. Thus it is essential to develop methods to aid early detection. This study aimed to assess dental patients’ experiences and awareness of oral cancer and screening within general dental practice. Methods A cross-sectional questionnaire survey of 184 English-speaking adults, with no previous history of oral cancer was conducted. The questionnaire collected data on participant’s knowledge of oral cancer, experience of ‘screening’, attitudes and feelings towards having a screening, anticipated help-seeking behaviours, health-related behaviours (particularly risk factors) and sociodemographics. Results Twenty percent of respondents had never heard of oral cancer; 77% knew little or nothing about it and 72% did not know that their Dentist routinely screens for oral cancer. Overall, attitudes to screening were positive. Ninety two percent of respondents would like their Dentist to tell them if they were being screened for signs of oral cancer and 97% would like help from their Dentists to reduce their risk. Conclusion Patients seem generally unaware of oral cancer screening by their dentist but are happy to take part in screening, would like to be informed, and welcome the support of their Dentist to reduce their risk of developing oral cancer. PMID:23249393
Maxwell, Annette E; Danao, Leda L; Bastani, Roshan
Filipino Americans underutilize life-saving screening tests for colorectal cancer, resulting in late stage of diagnosis and poor survival relative to other racial/ethnic groups. Education regarding colorectal cancer screening and distribution of free fecal occult blood test (FOBT) kits are evidence-based interventions that can significantly increase screening. However, this community will only benefit if the intervention is broadly disseminated. We assessed the feasibility of promoting colorectal cancer screening in Filipino American community settings working with community health advisors, and the practicality of conducting one-on-one or small group education, in addition to passing out free FOBT kits. Twenty community health advisors from 4 organizations engaged in recruitment and education activities with 132 participants. Community health advisors consistently completed screening questionnaires to establish eligibility and kept logs of FOBT distribution. However, they did not consistently record eligible participants who did not consent to participate. Process checklists that indicated what information was covered in each educational session and postsession follow-up logs were partially completed. Almost all participants reported receipt of intervention components and receipt of screening at 4-month follow-up and reported high acceptability of the program. The pilot study established the feasibility of working with community health advisors to promote colorectal cancer screening in Filipino American community settings. Findings informed the design of a dissemination trial that is currently ongoing with regards to monitoring recruitment, intervention implementation and follow-up and allowing flexibility regarding one-on-one or small group education.
van der Waal, Daniëlle; Ripping, Theodora M; Verbeek, André L M; Broeders, Mireille J M
Breast cancer screening is known to reduce breast cancer mortality. A high breast density may affect this reduction. We assessed the effect of screening on breast cancer mortality in women with dense and fatty breasts separately. Analyses were performed within the Nijmegen (Dutch) screening programme (1975-2008), which invites women (aged 50-74 years) biennially. Performance measures were determined. Furthermore, a case-control study was performed for women having dense and women having fatty breasts. Breast density was assessed visually with a dichotomized Wolfe scale. Breast density data were available for cases. The prevalence of dense breasts among controls was estimated with age-specific rates from the general population. Sensitivity analyses were performed on these estimates. Screening performance was better in the fatty than in the dense group (sensitivity 75.7% vs 57.8%). The mortality reduction appeared to be smaller for women with dense breasts, with an odds ratio (OR) of 0.87 (95% CI 0.52-1.45) in the dense and 0.59 (95% CI 0.44-0.79) in the fatty group. We can conclude that high density results in lower screening performance and appears to be associated with a smaller mortality reduction. Breast density is thus a likely candidate for risk-stratified screening. More research is needed on the association between density and screening harms. © 2016 UICC.
Bunyoz, Kristine Ifigenia; Krarup, Henrik; Weis, Nina
INTRODUCTION: Difficulty in identifying patients who are at risk for hepatitis B virus (HBV) reactivation makes it import-ant to screen for HBV before initiating immunosuppressive therapy. The aim of this study was to investigate screening procedures for HBV infection before initiation of immunos......INTRODUCTION: Difficulty in identifying patients who are at risk for hepatitis B virus (HBV) reactivation makes it import-ant to screen for HBV before initiating immunosuppressive therapy. The aim of this study was to investigate screening procedures for HBV infection before initiation...... of immunosuppressive therapy and to explore HBV treatment strategies. METHODS: All Danish units of haematology, oncology, dermatology, rheumatology and gastroenterology using immunosuppressive agents were invited to fill out a questionnaire for The Danish Database for Hepatitis B and C. RESULTS: A total of 28 (53...
Tekes, Gergely; Spies, Danica; Bank-Wolf, Barbara; Thiel, Volker; Thiel, Heinz-Jürgen
Feline infectious peritonitis (FIP) is a lethal immunopathological disease caused by feline coronaviruses (FCoVs). Here, we describe a reverse genetics approach to study FIP by assessing the pathogenicity of recombinant type I and type II and chimeric type I/type II FCoVs. All recombinant FCoVs established productive infection in cats, and recombinant type II FCoV (strain 79-1146) induced FIP. Virus sequence analyses from FIP-diseased cats revealed that the 3c gene stop codon of strain 79-1146 has changed to restore a full-length open reading frame (ORF).