The Experts below are selected from a list of 66849 Experts worldwide ranked by ideXlab platform

George P Patrinos - One of the best experts on this subject based on the ideXlab platform.

  • ashkenazi jewish genomic variants integrating data from the israeli national Genetic Database and gnomad
    Genetics in Medicine, 2018
    Co-Authors: Joel Zlotogora, George P Patrinos, Vardiella Meiner
    Abstract:

    The aim of the study was to compare the data for mutations related to clinical disorders reported among Ashkenazi Jewish patients in the Israeli National Genetic Database (INGD) with variants included in the Genome Aggregation Database (gnomAD). We extracted data for mutations claimed to cause disorders reported among Ashkenazi Jews from the INGD and searched gnomAD for each of them. We compared the allele frequency of each variant in Ashkenazi Jews with that of other delineated populations. Of the 58 INGD-reported mutations related to autosomal-dominant disorders, 19 were present in gnomAD (32.8%). Of the 309 mutations related to autosomal-recessive disorders, 240 (77.7%) were variants found in gnomAD. Of these variants, 202 (84.2%) were documented among one or more Ashkenazi individuals. At this point in the INGD, there are 168 Ashkenazi assumed founder mutations in 128 different genes corresponding to 111 autosomal-recessive disorders. Integration of information on mutations among Ashkenazi Jews extracted from the INGD with their population frequency recorded in gnomAD is important for effective straightforward molecular diagnosis as well as for targeted carrier screening either for reproductive decision-making or for implementation of disease-modifying behavior.

  • documentation of inherited disorders and mutation frequencies in the different religious communities in israel in the israeli national Genetic Database
    Human Mutation, 2007
    Co-Authors: Joel Zlotogora, Sjozef Van Baal, George P Patrinos
    Abstract:

    The National and Ethnic Mutation Databases (NEMDBs) are continuously updated mutation depositories that contain extensive information on the described Genetic heterogeneity of an ethnic group or population. Here, we report the construction of the Israeli National Genetic Database (Available at: www.goldenhelix.org/israeli; Last accessed: 20 April 2007) to document the sheer Genetic heterogeneity found in the Jewish and non-Jewish populations in Israel. The Database is built and maintained online using a newly developed customized version of the ETHNOS platform. The Israeli NEMDB is the richest in information among individual NEMDB, containing summaries of 347 Genetic disorders studied for the Israeli populations with numerous relevant references and links to the respective Online Mendelian Inheritance in Man (OMIM) entries. Summaries can be selected from an alphabetical summary index or queried using a keyword-based search functionality. An easy-to-use query interface provides access to the over 600 entries on allelic and carrier frequencies of the different mutations responsible for certain inherited disorders in the Jewish and non-Jewish populations, although such documentation is not as extensive as in the other ETHNOS-based NEMDBs. Also, the Israeli NEMDB provides a comprehensive listing of all laboratories providing molecular Genetic testing services in Israel with a separate query interface for the user to select which Genetic service is provided to a certain laboratory. The Israeli NEMDB is a useful user-friendly and extendable online resource for Genetic services in Israel, while the modified version of the ETHNOS software can be particularly useful for similar projects in other populations. Hum Mutat 28(10), 944–949, 2007. © 2007 Wiley-Liss, Inc.

Hoyng C.b. - One of the best experts on this subject based on the ideXlab platform.

  • Increased pro-MMP9 plasma levels are associated with neovascular age-related macular degeneration and with the risk allele of rs142450006 near MMP9
    2021
    Co-Authors: Lauwen S., Hoyng C.b., Fauser S., Lefeber D.j., Hollander, A.i. Den
    Abstract:

    Item does not contain fulltextPURPOSE: To evaluate the plasma levels of matrix metalloproteinase 9 (MMP9) and tissue inhibitors of metalloproteinase 3 (TIMP3) in neovascular age-related macular degeneration (nAMD) patients compared to controls, and to explore the potential effect of AMD-associated Genetic variants on MMP9 and TIMP3 protein levels. METHODS: nAMD and control patients were selected from the European Genetic Database (EUGENDA) based on different genotypes of rs142450006 near MMP9 and rs5754227 near TIMP3. Plasma total MMP9, active MMP9 and TIMP3 levels were measured using the enzyme linked immunosorbent assay (ELISA) and compared between nAMD patients and controls, as well as between different genotype groups. RESULTS: nAMD patients had significantly higher total MMP9 levels compared to controls (median 46.58 versus 26.90 ng/ml; p = 0.0004). In addition, the median MMP9 level in the homozygous genotype group for the AMD-risk allele (44.23 ng/ml) was significantly higher than the median for the heterozygous genotype group (26.90 ng/ml; p = 0.0082) and the median for the homozygous group for the non-risk allele (28.55 ng/ml; p = 0.0355). No differences were detected for the active MMP9. TIMP3 levels did not significantly differ between the AMD and control groups, nor between the different genotype groups for rs5754227. CONCLUSIONS: The results of our MMP9 analyses indicate that nAMD patients have on average higher systemic MMP9 levels than control individuals, and that this is partly driven by the rs142450006 variant near MMP9. This finding might be an interesting starting point for further exploration of MMP9 as a therapeutic target in nAMD, particularly among individuals carrying the risk-conferring allele rs142450006

  • Increased pro-MMP9 plasma levels are associated with neovascular age-related macular degeneration and with the risk allele of rs142450006 near MMP9
    2021
    Co-Authors: Lauwen S., Hoyng C.b., Fauser S., Lefeber D.j., Hollander, A.i. Den
    Abstract:

    Contains fulltext : 235020.pdf (Publisher’s version ) (Closed access)PURPOSE: To evaluate the plasma levels of matrix metalloproteinase 9 (MMP9) and tissue inhibitors of metalloproteinase 3 (TIMP3) in neovascular age-related macular degeneration (nAMD) patients compared to controls, and to explore the potential effect of AMD-associated Genetic variants on MMP9 and TIMP3 protein levels. METHODS: nAMD and control patients were selected from the European Genetic Database (EUGENDA) based on different genotypes of rs142450006 near MMP9 and rs5754227 near TIMP3. Plasma total MMP9, active MMP9 and TIMP3 levels were measured using the enzyme linked immunosorbent assay (ELISA) and compared between nAMD patients and controls, as well as between different genotype groups. RESULTS: nAMD patients had significantly higher total MMP9 levels compared to controls (median 46.58 versus 26.90 ng/ml; p = 0.0004). In addition, the median MMP9 level in the homozygous genotype group for the AMD-risk allele (44.23 ng/ml) was significantly higher than the median for the heterozygous genotype group (26.90 ng/ml; p = 0.0082) and the median for the homozygous group for the non-risk allele (28.55 ng/ml; p = 0.0355). No differences were detected for the active MMP9. TIMP3 levels did not significantly differ between the AMD and control groups, nor between the different genotype groups for rs5754227. CONCLUSIONS: The results of our MMP9 analyses indicate that nAMD patients have on average higher systemic MMP9 levels than control individuals, and that this is partly driven by the rs142450006 variant near MMP9. This finding might be an interesting starting point for further exploration of MMP9 as a therapeutic target in nAMD, particularly among individuals carrying the risk-conferring allele rs142450006

  • Phenotype Characteristics of Patients With Age-Related Macular Degeneration Carrying a Rare Variant in the Complement Factor H Gene
    'American Medical Association (AMA)', 2017
    Co-Authors: Kersten E., Geerlings M.j., Hollander, A.i. Den, E.k. De ,jong, Fauser S., Peto T., Hoyng C.b.
    Abstract:

    Item does not contain fulltextImportance: Rare variants in the complement factor H (CFH) gene and their association with age-related macular degeneration (AMD) have been described. However, there is limited literature on the phenotypes accompanying these rare variants. Phenotypical characteristics could help ophthalmologists select patients for additional Genetic testing. Objective: To describe the phenotypical characteristics of patients with AMD carrying a rare variant in the CFH gene. Design, Setting, and Participants: In this cross-sectional study, we searched the Genetic Database of the department of ophthalmology at the Radboudumc (tertiary ophthalmologic referral center) and the European Genetic Database for patients with AMD with a rare Genetic variant in the CFH gene. Patient recruitment took place from March 30, 2006, to February 18, 2013, and data were analyzed from November 30, 2015, to May 8, 2017. Phenotypical features on fundus photographs of both eyes of patients were graded by 2 independent reading center graders masked for carrier status. Main Outcomes and Measures: Differences in phenotypical characteristics between rare variant carriers and noncarriers were analyzed using univariable generalized estimated equations logistic regression models accounting for intereye correlation. Results: Analyses included 100 eyes of 51 patients with AMD carrying a CFH variant (mean [SD] age, 66.7 [12.1] years; 64.7% female) and 204 eyes of 102 age-matched noncarriers (mean [SD] age, 67.1 [11.8] years; 54.9% female). Carrying a rare pathogenic CFH variant was associated with larger drusen area (odds ratio range, 6.98 [95% CI, 2.04-23.89] to 18.50 [95% CI, 2.19-155.99]; P = .002), presence of drusen with crystalline appearance (odds ratio, 3.24; 95% CI, 1.24-8.50; P = .02), and drusen nasal to the optic disc (odds ratio range, 4.03 [95% CI, 1.70-9.56] to 7.42 [95% CI, 0.65-84.84]; P = .003). Conclusions and Relevance: Identification of rare CFH variant carriers may be important for upcoming complement-inhibiting therapies. Patients with an extensive drusen area, drusen with crystalline appearance, and drusen nasal to the optic disc are more likely to have a rare variant in the CFH gene. However, it is not likely that carriers can be discriminated from noncarriers based solely on phenotypical characteristics from color fundus images. Therefore, ophthalmologists should consider Genetic testing in patients with these phenotypic characteristics in combination with other patient characteristics, such as early onset, cuticular drusen on fluorescein angiography, and family history of AMD

  • Phenotype Characteristics of Patients With Age-Related Macular Degeneration Carrying a Rare Variant in the Complement Factor H Gene
    2017
    Co-Authors: Kersten E., Geerlings M.j., Hollander, A.i. Den, E.k. De ,jong, Fauser S., Peto T., Hoyng C.b.
    Abstract:

    Importance: Rare variants in the complement factor H (CFH) gene and their association with age-related macular degeneration (AMD) have been described. However, there is limited literature on the phenotypes accompanying these rare variants. Phenotypical characteristics could help ophthalmologists select patients for additional Genetic testing. Objective: To describe the phenotypical characteristics of patients with AMD carrying a rare variant in the CFH gene. Design, Setting, and Participants: In this cross-sectional study, we searched the Genetic Database of the department of ophthalmology at the Radboudumc (tertiary ophthalmologic referral center) and the European Genetic Database for patients with AMD with a rare Genetic variant in the CFH gene. Patient recruitment took place from March 30, 2006, to February 18, 2013, and data were analyzed from November 30, 2015, to May 8, 2017. Phenotypical features on fundus photographs of both eyes of patients were graded by 2 independent reading center graders masked for carrier status. Main Outcomes and Measures: Differences in phenotypical characteristics between rare variant carriers and noncarriers were analyzed using univariable generalized estimated equations logistic regression models accounting for intereye correlation. Results: Analyses included 100 eyes of 51 patients with AMD carrying a CFH variant (mean [SD] age, 66.7 [12.1] years; 64.7% female) and 204 eyes of 102 age-matched noncarriers (mean [SD] age, 67.1 [11.8] years; 54.9% female). Carrying a rare pathogenic CFH variant was associated with larger drusen area (odds ratio range, 6.98 [95% CI, 2.04-23.89] to 18.50 [95% CI, 2.19-155.99]; P = .002), presence of drusen with crystalline appearance (odds ratio, 3.24; 95% CI, 1.24-8.50; P = .02), and drusen nasal to the optic disc (odds ratio range, 4.03 [95% CI, 1.70-9.56] to 7.42 [95% CI, 0.65-84.84]; P = .003). Conclusions and Relevance: Identification of rare CFH variant carriers may be important for upcoming complement-inhibiting therapies. Patients with an extensive drusen area, drusen with crystalline appearance, and drusen nasal to the optic disc are more likely to have a rare variant in the CFH gene. However, it is not likely that carriers can be discriminated from noncarriers based solely on phenotypical characteristics from color fundus images. Therefore, ophthalmologists should consider Genetic testing in patients with these phenotypic characteristics in combination with other patient characteristics, such as early onset, cuticular drusen on fluorescein angiography, and family history of AMD

Ajay N Sharma - One of the best experts on this subject based on the ideXlab platform.

  • species sex and geo location identification of seized tiger panthera tigris tigris parts in nepal a molecular forensic approach
    PLOS ONE, 2018
    Co-Authors: Dibesh Karmacharya, Adarsh Man Sherchan, Santosh Dulal, Prajwol Manandhar, Sulochana Manandhar, Jyoti Joshi, Susmita Bhattarai, Tarka Bhatta, Nagendra P Awasthi, Ajay N Sharma
    Abstract:

    : Tiger (Panthera tigris) populations are in danger across their entire range due to habitat loss, poaching and the demand for tiger parts. The Bengal tiger (Panthera tigris tigris) is an endangered apex predator with a population size estimated to be less than 200 in Nepal. In spite of strict wildlife protection laws, illegal trade of tiger parts is increasing; and Nepal has become one of the major sources and transit routes for poached wildlife parts. Identification of wildlife parts is often challenging for law enforcement officials due to inadequate training and lack of available tools. Here, we describe a molecular forensic approach to gain insight into illegally trafficked tiger parts seized across Nepal. We created Nepal's first comprehensive reference Genetic Database of wild tigers through the Nepal Tiger Genome Project (2011-2013). This Database has nuclear DNA microsatellite genotype and sex profiles, including geo-spatial information, of over 60% (n = 120) of the wild tigers of Nepal. We analyzed 15 putative cases of confiscated poached tiger parts and all were confirmed to be of tiger. Ten samples were identified as male and five were female. We determined probable geo-source location for 9 of the 14 samples with 6-8 nuclear DNA microsatellite loci using inferences from four different statistical assignment methods. Six samples were assigned to Bardia National Park and one of these was an exact match to a female tiger previously profiled in our fecal DNA reference Database. Two tiger samples were assigned to Shuklaphanta Wildlife Reserve and one to Chitwan National Park. We are unable to definitively assign five tiger samples which could be offspring dispersers or might have come from tiger population outside of Nepal. Our study revealed that the western region, particularly Bardia National Park, is a poaching hotspot for illegal tiger trade in Nepal. We present feasibility of using molecular forensic based evidence to incriminate criminals in a court of law in the fight against wildlife crime.

  • Species, sex and geo-location identification of seized tiger (Panthera tigris tigris) parts in Nepal—A molecular forensic approach
    2018
    Co-Authors: Dibesh Karmacharya, Adarsh Man Sherchan, Santosh Dulal, Prajwol Manandhar, Sulochana Manandhar, Jyoti Joshi, Susmita Bhattarai, Tarka R. Bhatta, Nagendra Awasthi, Ajay N Sharma
    Abstract:

    Tiger (Panthera tigris) populations are in danger across their entire range due to habitat loss, poaching and the demand for tiger parts. The Bengal tiger (Panthera tigris tigris) is an endangered apex predator with a population size estimated to be less than 200 in Nepal. In spite of strict wildlife protection laws, illegal trade of tiger parts is increasing; and Nepal has become one of the major sources and transit routes for poached wildlife parts. Identification of wildlife parts is often challenging for law enforcement officials due to inadequate training and lack of available tools. Here, we describe a molecular forensic approach to gain insight into illegally trafficked tiger parts seized across Nepal. We created Nepal’s first comprehensive reference Genetic Database of wild tigers through the Nepal Tiger Genome Project (2011–2013). This Database has nuclear DNA microsatellite genotype and sex profiles, including geo-spatial information, of over 60% (n = 120) of the wild tigers of Nepal. We analyzed 15 putative cases of confiscated poached tiger parts and all were confirmed to be of tiger. Ten samples were identified as male and five were female. We determined probable geo-source location for 9 of the 14 samples with 6–8 nuclear DNA microsatellite loci using inferences from four different statistical assignment methods. Six samples were assigned to Bardia National Park and one of these was an exact match to a female tiger previously profiled in our fecal DNA reference Database. Two tiger samples were assigned to Shuklaphanta Wildlife Reserve and one to Chitwan National Park. We are unable to definitively assign five tiger samples which could be offspring dispersers or might have come from tiger population outside of Nepal. Our study revealed that the western region, particularly Bardia National Park, is a poaching hotspot for illegal tiger trade in Nepal. We present feasibility of using molecular forensic based evidence to incriminate criminals in a court of law in the fight against wildlife crime.

Dibesh Karmacharya - One of the best experts on this subject based on the ideXlab platform.

  • species sex and geo location identification of seized tiger panthera tigris tigris parts in nepal a molecular forensic approach
    PLOS ONE, 2018
    Co-Authors: Dibesh Karmacharya, Adarsh Man Sherchan, Santosh Dulal, Prajwol Manandhar, Sulochana Manandhar, Jyoti Joshi, Susmita Bhattarai, Tarka Bhatta, Nagendra P Awasthi, Ajay N Sharma
    Abstract:

    : Tiger (Panthera tigris) populations are in danger across their entire range due to habitat loss, poaching and the demand for tiger parts. The Bengal tiger (Panthera tigris tigris) is an endangered apex predator with a population size estimated to be less than 200 in Nepal. In spite of strict wildlife protection laws, illegal trade of tiger parts is increasing; and Nepal has become one of the major sources and transit routes for poached wildlife parts. Identification of wildlife parts is often challenging for law enforcement officials due to inadequate training and lack of available tools. Here, we describe a molecular forensic approach to gain insight into illegally trafficked tiger parts seized across Nepal. We created Nepal's first comprehensive reference Genetic Database of wild tigers through the Nepal Tiger Genome Project (2011-2013). This Database has nuclear DNA microsatellite genotype and sex profiles, including geo-spatial information, of over 60% (n = 120) of the wild tigers of Nepal. We analyzed 15 putative cases of confiscated poached tiger parts and all were confirmed to be of tiger. Ten samples were identified as male and five were female. We determined probable geo-source location for 9 of the 14 samples with 6-8 nuclear DNA microsatellite loci using inferences from four different statistical assignment methods. Six samples were assigned to Bardia National Park and one of these was an exact match to a female tiger previously profiled in our fecal DNA reference Database. Two tiger samples were assigned to Shuklaphanta Wildlife Reserve and one to Chitwan National Park. We are unable to definitively assign five tiger samples which could be offspring dispersers or might have come from tiger population outside of Nepal. Our study revealed that the western region, particularly Bardia National Park, is a poaching hotspot for illegal tiger trade in Nepal. We present feasibility of using molecular forensic based evidence to incriminate criminals in a court of law in the fight against wildlife crime.

  • Assessment of Genetic diversity, population structure, and gene flow of tigers (Panthera tigris tigris) across Nepal's Terai Arc Landscape
    2018
    Co-Authors: Dibesh Karmacharya
    Abstract:

    Nepal Tiger Genome Project (NTGP), a two year (June 2011- 2013) research project to build Genetic Database of wild Bengal tigers of Nepal. NTGP is a collaborative effort of Center for Molecular Dynamics Nepal, Nepal Government’s Ministry of Forest and Soil Conservation, Department of National Parks and Wildlife Conservation, University of Idaho and Virginia Tech University. The project introduced latest Genetic technology in Nepal for wildlife conservation and has built Nepal’s first geo-spatial Genetic Database of Bengal tigers from throughout the Terai Arc landscape. NTGP was made possible through generous funding support of the American people through USAID/Nepal under Fixed Obligation Grant (FOG) no. AID-367-G-11-00001. Conservation of the Bengal tigers in Nepal is a top priority due to its dwindling number of species worldwide. It is important to have a comprehensive understanding of tiger conservation from a landscape perspective. In order to develop effective policies and strategies for the conservation of Bengal tigers, effective census tools need to be developed and deployed. The conventional tools for conservation are often inadequate and ineffective to address the problem. NTGP introduced the latest in non-invasive Genetic technology to address many challenges of tiger conservation in Nepal. Due to its high specificity and sensitivity, information obtained through a Genetic study is more detailed than conventionally gathered data. It can also be applied to understand landscape Genetics of the species which has great utility for developing overall conservation policies and strategies on a landscape scale. In addition to introducing new Genetic technology in Nepal, NTGP also enhanced existing laboratory capacity and fostered an environment of conservation research collaboration in a global scale. A comprehensive Bengal tiger Genetic Database has been created with detailed field, laboratory and Genetic information on confirmed tiger samples. This elaborate searchable Database is designed to be highly secure and accessible only to the government with CMDN being the caretaker of the information; this Database has a greater utility for wildlife research and forensic purposes. NTGP has been able to leave a long lasting impact in the field of conservation Genetics in Nepal. The project itself has trained 75 local experts, created 43 jobs, brought in experts from 4 countries, and helped in five other similar researches in Nepal.

  • Species, sex and geo-location identification of seized tiger (Panthera tigris tigris) parts in Nepal—A molecular forensic approach
    2018
    Co-Authors: Dibesh Karmacharya, Adarsh Man Sherchan, Santosh Dulal, Prajwol Manandhar, Sulochana Manandhar, Jyoti Joshi, Susmita Bhattarai, Tarka R. Bhatta, Nagendra Awasthi, Ajay N Sharma
    Abstract:

    Tiger (Panthera tigris) populations are in danger across their entire range due to habitat loss, poaching and the demand for tiger parts. The Bengal tiger (Panthera tigris tigris) is an endangered apex predator with a population size estimated to be less than 200 in Nepal. In spite of strict wildlife protection laws, illegal trade of tiger parts is increasing; and Nepal has become one of the major sources and transit routes for poached wildlife parts. Identification of wildlife parts is often challenging for law enforcement officials due to inadequate training and lack of available tools. Here, we describe a molecular forensic approach to gain insight into illegally trafficked tiger parts seized across Nepal. We created Nepal’s first comprehensive reference Genetic Database of wild tigers through the Nepal Tiger Genome Project (2011–2013). This Database has nuclear DNA microsatellite genotype and sex profiles, including geo-spatial information, of over 60% (n = 120) of the wild tigers of Nepal. We analyzed 15 putative cases of confiscated poached tiger parts and all were confirmed to be of tiger. Ten samples were identified as male and five were female. We determined probable geo-source location for 9 of the 14 samples with 6–8 nuclear DNA microsatellite loci using inferences from four different statistical assignment methods. Six samples were assigned to Bardia National Park and one of these was an exact match to a female tiger previously profiled in our fecal DNA reference Database. Two tiger samples were assigned to Shuklaphanta Wildlife Reserve and one to Chitwan National Park. We are unable to definitively assign five tiger samples which could be offspring dispersers or might have come from tiger population outside of Nepal. Our study revealed that the western region, particularly Bardia National Park, is a poaching hotspot for illegal tiger trade in Nepal. We present feasibility of using molecular forensic based evidence to incriminate criminals in a court of law in the fight against wildlife crime.

Takumi Oti - One of the best experts on this subject based on the ideXlab platform.

  • the gastrin releasing peptide bombesin system revisited by a reverse evolutionary study considering xenopus
    Scientific Reports, 2021
    Co-Authors: Asuka Hirooka, Keiko Takanami, Mayuko Hamada, Daiki Fujiyama, Yasuhisa Kobayashi, Takumi Oti
    Abstract:

    Bombesin is a putative antibacterial peptide isolated from the skin of the frog, Bombina bombina. Two related (bombesin-like) peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been found in mammals. The history of GRP/bombesin discovery has caused little attention to be paid to the evolutionary relationship of GRP/bombesin and their receptors in vertebrates. We have classified the peptides and their receptors from the phyloGenetic viewpoint using a newly established Genetic Database and bioinformatics. Here we show, by using a clawed frog (Xenopus tropicalis), that GRP is not a mammalian counterpart of bombesin and also that, whereas the GRP system is widely conserved among vertebrates, the NMB/bombesin system has diversified in certain lineages, in particular in frog species. To understand the derivation of GRP system in the ancestor of mammals, we have focused on the GRP system in Xenopus. Gene expression analyses combined with immunohistochemistry and Western blotting experiments demonstrated that GRP peptides and their receptors are distributed in the brain and stomach of Xenopus. We conclude that GRP peptides and their receptors have evolved from ancestral (GRP-like peptide) homologues to play multiple roles in both the gut and the brain as one of the 'gut-brain peptide' systems.