Single Gene

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 570351 Experts worldwide ranked by ideXlab platform

Anver Kuliev - One of the best experts on this subject based on the ideXlab platform.

  • Preimplation Diagnosis for Single-Gene Disorders
    Practical Preimplantation Genetic Diagnosis, 2012
    Co-Authors: Anver Kuliev
    Abstract:

    Single-Gene disorders are the first group of indications for which preimplantation Genetic diagnosis (PGD) was originally introduced 21 years ago, with the purpose of performing Genetic testing before pregnancy, in order to establish only unaffected pregnancies and avoid the need for pregnancy termination, which is the major limitation of traditional prenatal diagnosis [1, 2]. Despite the requirement for ovarian hyperstimulation and in vitro fertilization (IVF), needed to perform Genetic testing of oocyte or embryo prior to transfer, PGD has been accepted in most parts of the world [3, 4]. At least 10,000 PGD cycles were performed for Single-Gene disorders and, as will be shown below, is presently offered for some indications that have never been practiced in prenatal diagnosis, such as late-onset diseases with Genetic predisposition, and preimplantation HLA typing, making PGD not only an alternative but also a complement to prenatal diagnosis [5–8]. The progress of PGD has been extensively reviewed, so the present book will mainly concentrate on those aspects of PGD that are useful for reproductive medicine and Genetics practices, including available PGD approaches for different groups of Genetic disorders, their accuracy, and major indications compared to prenatal diagnosis, and present practical details useful for the realization of PGD for each of the conditions described.

  • Single Gene testing combined with Single nucleotide polymorphism microarray preimplantation Genetic diagnosis for aneuploidy a novel approach in optimizing pregnancy outcome
    Fertility and Sterility, 2011
    Co-Authors: Paul R Brezina, Anver Kuliev, Svetlana Rechitsky, A T Benner, Ekaterina Pomerantseva, Dana Pauling, W G Kearns
    Abstract:

    Objective To describe a method of amplifying DNA from blastocyst trophectoderm cells (two or three cells) and simultaneously performing 23-chromosome Single nucleotide polymorphism microarrays and Single-Gene preimplantation Genetic diagnosis. Design Case report. Setting IVF clinic and preimplantation Genetic diagnostic centers. Patient(s) A 36-year-old woman, gravida 2, para 1011, and her husband who both were carriers of GM 1 gangliosidosis. The couple wished to proceed with microarray analysis for aneuploidy detection coupled with DNA sequencing for GM 1 gangliosidosis. Intervention(s) An IVF cycle was performed. Ten blastocyst-stage embryos underwent trophectoderm biopsy. Twenty-three–chromosome microarray analysis for aneuploidy and specific DNA sequencing for GM 1 gangliosidosis mutations were performed. Main Outcome Measure(s) Viable pregnancy. Result(s) After testing, elective Single embryo transfer was performed followed by an intrauterine pregnancy with documented fetal cardiac activity by ultrasound. Conclusion(s) Twenty-three–chromosome microarray analysis for aneuploidy detection and Single-Gene evaluation via specific DNA sequencing and linkage analysis are used for preimplantation diagnosis for Single-Gene disorders and aneuploidy. Because of the minimal amount of Genetic material obtained from the day 3 to 5 embryos (up to 6 pg), these modalities have been used in isolation of each other. The use of preimplantation Genetic diagnosis for aneuploidy coupled with testing for Single-Gene disorders via trophectoderm biopsy is a novel approach to maximize pregnancy outcomes. Although further investigation is warranted, preimplantation Genetic diagnosis for aneuploidy and Single-Gene testing seem destined to be used increasingly to optimize ultimate pregnancy success.

  • Current status of preimplantation diagnosis for Single Gene disorders.
    Reproductive BioMedicine Online, 2003
    Co-Authors: Yury Verlinsky, Anver Kuliev
    Abstract:

    Preimplantation Genetic diagnosis (PGD) has become an established procedure for avoiding the birth of affected children with Single Gene disorders. PGD is performed through polar body or blastomere biopsy, which has no deleterious effect on pre- and post-implantation development. This review describes the most recent developments and current changes in the spectrum of conditions for which PGD has been applied. The most recent applications of PGD include congenital malformations, blood group incompatibility and an increasing number of late onset disorders with Genetic predisposition, all of which have not previously been diagnosed using PGD. Despite ethical concerns, PGD has also been used for preselection of unaffected and HLA matched embryos, and recently for preimplantation HLA matching without testing for the causative Gene. This extends the practical value of PGD, with its utility being no longer limited to prevention of Single Gene disorders, by expanding it to treatment of siblings requiring stem cell transplantation.

  • accuracy of preimplantation diagnosis of Single Gene disorders by polar body analysis of oocytes
    Journal of Assisted Reproduction and Genetics, 1999
    Co-Authors: Svetlana Rechitsky, Anver Kuliev, Oleg Verlinsky, T. Amet, V. Ivakhnenko, V Kukharenko, C Strom, Yury Verlinsky
    Abstract:

    Purpose:A number of pitfalls in Single-cell DNA analysis, including undetected DNA contamination, undetected allele drop out, and preferential amplification, may lead to misdiagnosis in preimplantation Genetic diagnosis of Single-Gene disorders.

  • Accuracy of preimplantation diagnosis of Single-Gene disorders by polar body analysis of oocytes.
    Journal of Assisted Reproduction and Genetics, 1999
    Co-Authors: Svetlana Rechitsky, Anver Kuliev, Oleg Verlinsky, Charles M. Strom, T. Amet, V. Ivakhnenko, V Kukharenko, Yury Verlinsky
    Abstract:

    Purpose: A number of pitfalls in Single-cell DNA analysis, including undetected DNA contamination, undetected allele drop out, and preferential amplification, may lead to misdiagnosis in preimplantation Genetic diagnosis of Single-Gene disorders. Methods: Preimplantation Genetic diagnosis was performed by sequential first and second polar body analysis of oocytes in 26 couples at risk for having children with various Single-Gene disorders. Mutant Genes were amplified simultaneously with linked polymorphic markers, and only embryos resulting from the mutation-free oocytes predicted by polar body analysis with confirmation by polymorphic marker testing were transferred back to patients. Results: Overall 529 oocytes from 48 clinical cycles (26 patients) were tested, resulting in the transfer of 106 embryos in 44 clinical cycles. As many as 46 (9.6%) instances of allele dropout were observed, the majority (96%) of which were detected. Seventeen unaffected pregnancies were established, of which nine resulted in the birth of an unaffected child, and the rest are ongoing. Conclusions: A high accuracy of preimplantation Genetic diagnosis of Single-Gene disorders is achieved by application of sequential analysis of the first and second polar body and multiplex polymerase chain reaction.

Svetlana Rechitsky - One of the best experts on this subject based on the ideXlab platform.

  • Single Gene testing combined with Single nucleotide polymorphism microarray preimplantation Genetic diagnosis for aneuploidy a novel approach in optimizing pregnancy outcome
    Fertility and Sterility, 2011
    Co-Authors: Paul R Brezina, Anver Kuliev, Svetlana Rechitsky, A T Benner, Ekaterina Pomerantseva, Dana Pauling, W G Kearns
    Abstract:

    Objective To describe a method of amplifying DNA from blastocyst trophectoderm cells (two or three cells) and simultaneously performing 23-chromosome Single nucleotide polymorphism microarrays and Single-Gene preimplantation Genetic diagnosis. Design Case report. Setting IVF clinic and preimplantation Genetic diagnostic centers. Patient(s) A 36-year-old woman, gravida 2, para 1011, and her husband who both were carriers of GM 1 gangliosidosis. The couple wished to proceed with microarray analysis for aneuploidy detection coupled with DNA sequencing for GM 1 gangliosidosis. Intervention(s) An IVF cycle was performed. Ten blastocyst-stage embryos underwent trophectoderm biopsy. Twenty-three–chromosome microarray analysis for aneuploidy and specific DNA sequencing for GM 1 gangliosidosis mutations were performed. Main Outcome Measure(s) Viable pregnancy. Result(s) After testing, elective Single embryo transfer was performed followed by an intrauterine pregnancy with documented fetal cardiac activity by ultrasound. Conclusion(s) Twenty-three–chromosome microarray analysis for aneuploidy detection and Single-Gene evaluation via specific DNA sequencing and linkage analysis are used for preimplantation diagnosis for Single-Gene disorders and aneuploidy. Because of the minimal amount of Genetic material obtained from the day 3 to 5 embryos (up to 6 pg), these modalities have been used in isolation of each other. The use of preimplantation Genetic diagnosis for aneuploidy coupled with testing for Single-Gene disorders via trophectoderm biopsy is a novel approach to maximize pregnancy outcomes. Although further investigation is warranted, preimplantation Genetic diagnosis for aneuploidy and Single-Gene testing seem destined to be used increasingly to optimize ultimate pregnancy success.

  • accuracy of preimplantation diagnosis of Single Gene disorders by polar body analysis of oocytes
    Journal of Assisted Reproduction and Genetics, 1999
    Co-Authors: Svetlana Rechitsky, Anver Kuliev, Oleg Verlinsky, T. Amet, V. Ivakhnenko, V Kukharenko, C Strom, Yury Verlinsky
    Abstract:

    Purpose:A number of pitfalls in Single-cell DNA analysis, including undetected DNA contamination, undetected allele drop out, and preferential amplification, may lead to misdiagnosis in preimplantation Genetic diagnosis of Single-Gene disorders.

  • prepregnancy testing for Single Gene disorders by polar body analysis
    Genetic Testing, 1999
    Co-Authors: Yury Verlinsky, Svetlana Rechitsky, Oleg Verlinsky, V Ivachnenko, A Lifchez, B Kaplan, J Moise, J Valle, A Borkowski, J Nefedova
    Abstract:

    Preventive measures for Single-Gene disorders are currently based on carrier screening in pregnancy and prenatal diagnosis. Although this has been extremely effective for preventing new cases of common inherited conditions, the major limitation is still termination of 25% of wanted pregnancies following detection of affected fetuses. To overcome this important problem, we developed a method for prepregnancy Genetic testing that involves DNA analysis of the first and second polar bodies, which are extruded during maturation and fertilization of oocytes. We offered this option to 28 couples at risk for having children with Single-Gene disorders. Fifty clinical cycles were performed from these patients for the following conditions: 20 for cystic fibrosis, 18 for thalassemia, 6 for sickle cell disease, 2 each for Gaucher disease and LCHAD (long-chain 3-hydroxyacyl-COA dehydrogenase deficiency), and 1 each for hemophilia B and phenylketonuria. Oocytes obtained from these patients using in vitro fertilization p...

  • Accuracy of preimplantation diagnosis of Single-Gene disorders by polar body analysis of oocytes.
    Journal of Assisted Reproduction and Genetics, 1999
    Co-Authors: Svetlana Rechitsky, Anver Kuliev, Oleg Verlinsky, Charles M. Strom, T. Amet, V. Ivakhnenko, V Kukharenko, Yury Verlinsky
    Abstract:

    Purpose: A number of pitfalls in Single-cell DNA analysis, including undetected DNA contamination, undetected allele drop out, and preferential amplification, may lead to misdiagnosis in preimplantation Genetic diagnosis of Single-Gene disorders. Methods: Preimplantation Genetic diagnosis was performed by sequential first and second polar body analysis of oocytes in 26 couples at risk for having children with various Single-Gene disorders. Mutant Genes were amplified simultaneously with linked polymorphic markers, and only embryos resulting from the mutation-free oocytes predicted by polar body analysis with confirmation by polymorphic marker testing were transferred back to patients. Results: Overall 529 oocytes from 48 clinical cycles (26 patients) were tested, resulting in the transfer of 106 embryos in 44 clinical cycles. As many as 46 (9.6%) instances of allele dropout were observed, the majority (96%) of which were detected. Seventeen unaffected pregnancies were established, of which nine resulted in the birth of an unaffected child, and the rest are ongoing. Conclusions: A high accuracy of preimplantation Genetic diagnosis of Single-Gene disorders is achieved by application of sequential analysis of the first and second polar body and multiplex polymerase chain reaction.

Ian Bone - One of the best experts on this subject based on the ideXlab platform.

  • Single Gene disorders causing ischaemic stroke
    Journal of Neurology, 2006
    Co-Authors: Saif S. M. Razvi, Ian Bone
    Abstract:

    Stroke is the third most common cause of death and the leading cause of long-term neurological disability in the world. Conventional vascular risk factors for stroke contribute approximately to only forty to fifty percent of stroke risk. Genetic factors may therefore contribute to a significant proportion of stroke and may be polygenic, monogenic or multi-factorial. Monogenic (Single Gene) disorders may potentially account for approximately one percent of all ischaemic stroke. Monogenic stroke disorders include conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) and hereditary endotheliopathy, retinopathy, nephropathy and stroke (HERNS). In addition, other monogenic conditions such as sickle cell and Fabry disease also lead to stroke. These monogenic disorders cause either small vessel or large vessel stroke (or a combination of both) and serve as useful models for understanding and studying conventional stroke and cerebrovascular disease and its accompaniments such as vascular dementia.

Yury Verlinsky - One of the best experts on this subject based on the ideXlab platform.

  • Current status of preimplantation diagnosis for Single Gene disorders.
    Reproductive BioMedicine Online, 2003
    Co-Authors: Yury Verlinsky, Anver Kuliev
    Abstract:

    Preimplantation Genetic diagnosis (PGD) has become an established procedure for avoiding the birth of affected children with Single Gene disorders. PGD is performed through polar body or blastomere biopsy, which has no deleterious effect on pre- and post-implantation development. This review describes the most recent developments and current changes in the spectrum of conditions for which PGD has been applied. The most recent applications of PGD include congenital malformations, blood group incompatibility and an increasing number of late onset disorders with Genetic predisposition, all of which have not previously been diagnosed using PGD. Despite ethical concerns, PGD has also been used for preselection of unaffected and HLA matched embryos, and recently for preimplantation HLA matching without testing for the causative Gene. This extends the practical value of PGD, with its utility being no longer limited to prevention of Single Gene disorders, by expanding it to treatment of siblings requiring stem cell transplantation.

  • accuracy of preimplantation diagnosis of Single Gene disorders by polar body analysis of oocytes
    Journal of Assisted Reproduction and Genetics, 1999
    Co-Authors: Svetlana Rechitsky, Anver Kuliev, Oleg Verlinsky, T. Amet, V. Ivakhnenko, V Kukharenko, C Strom, Yury Verlinsky
    Abstract:

    Purpose:A number of pitfalls in Single-cell DNA analysis, including undetected DNA contamination, undetected allele drop out, and preferential amplification, may lead to misdiagnosis in preimplantation Genetic diagnosis of Single-Gene disorders.

  • prepregnancy testing for Single Gene disorders by polar body analysis
    Genetic Testing, 1999
    Co-Authors: Yury Verlinsky, Svetlana Rechitsky, Oleg Verlinsky, V Ivachnenko, A Lifchez, B Kaplan, J Moise, J Valle, A Borkowski, J Nefedova
    Abstract:

    Preventive measures for Single-Gene disorders are currently based on carrier screening in pregnancy and prenatal diagnosis. Although this has been extremely effective for preventing new cases of common inherited conditions, the major limitation is still termination of 25% of wanted pregnancies following detection of affected fetuses. To overcome this important problem, we developed a method for prepregnancy Genetic testing that involves DNA analysis of the first and second polar bodies, which are extruded during maturation and fertilization of oocytes. We offered this option to 28 couples at risk for having children with Single-Gene disorders. Fifty clinical cycles were performed from these patients for the following conditions: 20 for cystic fibrosis, 18 for thalassemia, 6 for sickle cell disease, 2 each for Gaucher disease and LCHAD (long-chain 3-hydroxyacyl-COA dehydrogenase deficiency), and 1 each for hemophilia B and phenylketonuria. Oocytes obtained from these patients using in vitro fertilization p...

  • Accuracy of preimplantation diagnosis of Single-Gene disorders by polar body analysis of oocytes.
    Journal of Assisted Reproduction and Genetics, 1999
    Co-Authors: Svetlana Rechitsky, Anver Kuliev, Oleg Verlinsky, Charles M. Strom, T. Amet, V. Ivakhnenko, V Kukharenko, Yury Verlinsky
    Abstract:

    Purpose: A number of pitfalls in Single-cell DNA analysis, including undetected DNA contamination, undetected allele drop out, and preferential amplification, may lead to misdiagnosis in preimplantation Genetic diagnosis of Single-Gene disorders. Methods: Preimplantation Genetic diagnosis was performed by sequential first and second polar body analysis of oocytes in 26 couples at risk for having children with various Single-Gene disorders. Mutant Genes were amplified simultaneously with linked polymorphic markers, and only embryos resulting from the mutation-free oocytes predicted by polar body analysis with confirmation by polymorphic marker testing were transferred back to patients. Results: Overall 529 oocytes from 48 clinical cycles (26 patients) were tested, resulting in the transfer of 106 embryos in 44 clinical cycles. As many as 46 (9.6%) instances of allele dropout were observed, the majority (96%) of which were detected. Seventeen unaffected pregnancies were established, of which nine resulted in the birth of an unaffected child, and the rest are ongoing. Conclusions: A high accuracy of preimplantation Genetic diagnosis of Single-Gene disorders is achieved by application of sequential analysis of the first and second polar body and multiplex polymerase chain reaction.

Georg Seelig - One of the best experts on this subject based on the ideXlab platform.

  • microrna based Single Gene circuits buffer protein synthesis rates against perturbations
    ACS Synthetic Biology, 2014
    Co-Authors: Timothy Strovas, Alexander B Rosenberg, Brianna E Kuypers, Richard A Muscat, Georg Seelig
    Abstract:

    Achieving precise control of mammalian transGene expression has remained a long-standing, and increasingly urgent, challenge in biomedical science. Despite much work, Single-cell methods have consistently revealed that mammalian Gene expression levels remain susceptible to fluctuations (noise) and external perturbations. Here, we show that precise control of protein synthesis can be realized using a Single-Gene microRNA (miRNA)-based feed-forward loop (sgFFL). This minimal autoregulatory Gene circuit consists of an intronic miRNA that targets its own transcript. In response to a step-like increase in transcription rate, the network Generated a transient protein expression pulse before returning to a lower steady state level, thus exhibiting adaptation. Critically, the steady state protein levels were independent of the size of the stimulus, demonstrating that this simple network architecture effectively buffered protein production against changes in transcription. The Single-Gene network architecture was also effective in buffering against transcriptional noise, leading to reduced cell-to-cell variability in protein synthesis. Noise was up to 5-fold lower for a sgFFL than for an unregulated control Gene with equal mean protein levels. The noise buffering capability varied predictably with the strength of the miRNA-target interaction. Together, these results suggest that the sgFFL Single-Gene motif provides a General and broadly applicable platform for robust Gene expression in synthetic and natural Gene circuits.