Literatura académica sobre el tema "Pathogenic variant"
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Artículos de revistas sobre el tema "Pathogenic variant"
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Civan, Hasret A. y Serhat Seyhan. "Molecular Heterogeneity in Cystic Fibrosis". Journal of Pediatric Genetics 09, n.º 03 (17 de febrero de 2020): 171–76. http://dx.doi.org/10.1055/s-0040-1701646.
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AbstractWe aimed to evaluate type, frequency, and variety of pathogenic variants according to clinical and demographic features of children diagnosed with cystic fibrosis (CF). Twenty-five CF patients were evaluated retrospectively. Patients' demographics, physical examination, imaging, laboratory, and molecular pathogenic variant analysis findings were evaluated. Phe508del was the most frequently (33.3%) detected pathogenic variant, followed by point pathogenic variants E92K, 1898 + lGA/7T/7T, and 2789 + 5GA, respectively. Statistically higher rates of pathogenic variants were detected in male patients. The most frequently detected pathogenic variant was Phe508del. The identification of nine additional pathogenic variants of Phe508del revealed the heterogeneous nature of the CF.
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Alenezi, Wejdan M., Caitlin T. Fierheller, Timothée Revil, Corinne Serruya, Anne-Marie Mes-Masson, William D. Foulkes, Diane Provencher, Zaki El Haffaf, Jiannis Ragoussis y Patricia N. Tonin. "Case Review: Whole-Exome Sequencing Analyses Identify Carriers of a Known Likely Pathogenic Intronic BRCA1 Variant in Ovarian Cancer Cases Clinically Negative for Pathogenic BRCA1 and BRCA2 Variants". Genes 13, n.º 4 (15 de abril de 2022): 697. http://dx.doi.org/10.3390/genes13040697.
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Background: Detecting pathogenic intronic variants resulting in aberrant splicing remains a challenge in routine genetic testing. We describe germline whole-exome sequencing (WES) analyses and apply in silico predictive tools of familial ovarian cancer (OC) cases reported clinically negative for pathogenic BRCA1 and BRCA2 variants. Methods: WES data from 27 familial OC cases reported clinically negative for pathogenic BRCA1 and BRCA2 variants and 53 sporadic early-onset OC cases were analyzed for pathogenic variants in BRCA1 or BRCA2. WES data from carriers of pathogenic BRCA1 or BRCA2 variants were analyzed for pathogenic variants in 10 other OC predisposing genes. Loss of heterozygosity analysis was performed on tumor DNA from variant carriers. Results: BRCA1 c.5407-25T>A intronic variant, identified in two affected sisters and one sporadic OC case, is predicted to create a new splice effecting transcription of BRCA1. WES data from BRCA1 c.5407-25T>A carriers showed no evidence of pathogenic variants in other OC predisposing genes. Sequencing the tumor DNA from the variant carrier showed complete loss of the wild-type allele. Conclusions: The findings support BRCA1 c.5407-25T>A as a likely pathogenic variant and highlight the importance of investigating intronic sequences as causal variants in OC families where the involvement of BRCA1 is highly suggestive.
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Du, Juanjiangmeng, Monica Sudarsanam, Eduardo Pérez-Palma, Andrea Ganna, Laurent Francioli, Sumaiya Iqbal, Lisa-Marie Niestroj et al. "Variant Score Ranker—a web application for intuitive missense variant prioritization". Bioinformatics 35, n.º 21 (25 de abril de 2019): 4478–79. http://dx.doi.org/10.1093/bioinformatics/btz252.
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Abstract Motivation The correct classification of missense variants as benign or pathogenic remains challenging. Pathogenic variants are expected to have higher deleterious prediction scores than benign variants in the same gene. However, most of the existing variant annotation tools do not reference the score range of benign population variants on gene level. Results We present a web-application, Variant Score Ranker, which enables users to rapidly annotate variants and perform gene-specific variant score ranking on the population level. We also provide an intuitive example of how gene- and population-calibrated variant ranking scores can improve epilepsy variant prioritization. Availability and implementation http://vsranker.broadinstitute.org Supplementary information Supplementary data are available at Bioinformatics online.
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Wiggins, George A. R., Logan C. Walker y John F. Pearson. "Genome-Wide Gene Expression Analyses of BRCA1- and BRCA2-Associated Breast and Ovarian Tumours". Cancers 12, n.º 10 (16 de octubre de 2020): 3015. http://dx.doi.org/10.3390/cancers12103015.
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Germline pathogenic variants in BRCA1 and BRCA2 increase cumulative lifetime risk up to 75% for breast cancer and 76% for ovarian cancer. Genetic testing for BRCA1 and BRCA2 pathogenic variants has become an important part of clinical practice for cancer risk assessment and for reducing individual risk of developing cancer. Genetic testing can produce three outcomes: positive (a pathogenic variant), uninformative (no pathogenic variant) and uncertain significance (a variant of unknown clinical significance). More than one third of BRCA1 and BRCA2 variants identified have been classified as variants of uncertain significance, presenting a challenge for clinicians. To address this important clinical challenge, a number of studies have been undertaken to establish a gene expression phenotype for pathogenic BRCA1 and BRCA2 variant carriers in several diseased and normal tissues. However, the consistency of gene expression phenotypes described in studies has been poor. To determine if gene expression analysis has been a successful approach for variant classification, we describe the design and comparability of 23 published gene expression studies that have profiled cells from BRCA1 and BRCA2 pathogenic variant carriers. We show the impact of advancements in expression-based technologies, the importance of developing larger study cohorts and the necessity to better understand variables affecting gene expression profiles across different tissue types.
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Safka Brozkova, Dana, Anna Uhrova Meszarosova, Petra Lassuthova, Lukáš Varga, David Staněk, Silvia Borecká, Jana Laštůvková et al. "The Cause of Hereditary Hearing Loss in GJB2 Heterozygotes—A Comprehensive Study of the GJB2/DFNB1 Region". Genes 12, n.º 5 (1 de mayo de 2021): 684. http://dx.doi.org/10.3390/genes12050684.
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Hearing loss is a genetically heterogeneous sensory defect, and the frequent causes are biallelic pathogenic variants in the GJB2 gene. However, patients carrying only one heterozygous pathogenic (monoallelic) GJB2 variant represent a long-lasting diagnostic problem. Interestingly, previous results showed that individuals with a heterozygous pathogenic GJB2 variant are two times more prevalent among those with hearing loss compared to normal-hearing individuals. This excess among patients led us to hypothesize that there could be another pathogenic variant in the GJB2 region/DFNB1 locus. A hitherto undiscovered variant could, in part, explain the cause of hearing loss in patients and would mean reclassifying them as patients with GJB2 biallelic pathogenic variants. In order to detect an unknown causal variant, we examined 28 patients using NGS with probes that continuously cover the 0.4 Mb in the DFNB1 region. An additional 49 patients were examined by WES to uncover only carriers. We did not reveal a second pathogenic variant in the DFNB1 region. However, in 19% of the WES-examined patients, the cause of hearing loss was found to be in genes other than the GJB2. We present evidence to show that a substantial number of patients are carriers of the GJB2 pathogenic variant, albeit only by chance.
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Rao, Nandana D. y Brian H. Shirts. "Using species richness calculations to model the global profile of unsampled pathogenic variants: Examples from BRCA1 and BRCA2". PLOS ONE 18, n.º 2 (8 de febrero de 2023): e0278010. http://dx.doi.org/10.1371/journal.pone.0278010.
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There have been many surveys of genetic variation in BRCA1 and BRCA2 to identify variant prevalence and catalogue population specific variants, yet none have evaluated the magnitude of unobserved variation. We applied species richness estimation methods from ecology to estimate “variant richness” and determine how many germline pathogenic BRCA1/2 variants have yet to be identified and the frequency of these missing variants in different populations. We also estimated the prevalence of germline pathogenic BRCA1/2 variants and identified those expected to be most common. Data was obtained from a literature search including studies conducted globally that tested the entirety of BRCA1/2 for pathogenic variation. Across countries, 45% to 88% of variants were estimated to be missing, i.e., present in the population but not observed in study data. Estimated variant frequencies in each country showed a higher proportion of rare variants compared to recurrent variants. The median prevalence estimate of BRCA1/2 pathogenic variant carriers was 0.64%. BRCA1 c.68_69del is likely the most recurrent BRCA1/2 variant globally due to its estimated prevalence in India. Modeling variant richness using ecology methods may assist in evaluating clinical targeted assays by providing a picture of what is observed with estimates of what is still unknown.
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Kyo, Chika, Takeshi Usui, Rieko Kosugi, Mizuki Torii, Takako Yonemoto, Tatsuo Ogawa, Masato Kotani et al. "ARMC5 Alterations in Primary Macronodular Adrenal Hyperplasia (PMAH) and the Clinical State of Variant Carriers". Journal of the Endocrine Society 3, n.º 10 (23 de julio de 2019): 1837–46. http://dx.doi.org/10.1210/js.2019-00210.
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Abstract Context Primary macronodular adrenal hyperplasia (PMAH) is a rare type of Cushing or subclinical Cushing syndrome and is associated with bilateral multinodular formation. ARMC5 is one of the responsible genes for PMAH. Objectives This study was performed to identify the genotype-phenotype correlation of ARMC5 in a cohort of Japanese patients. Patients and Methods Fourteen patients with clinically diagnosed PMAH and family members of selected patients were studied for ARMC5 gene alteration and clinical phenotype. The associated nonadrenal tumor tissues were also studied. Results Of fourteen patients with PMAH, 10 had pathogenic or likely pathogenic variants of ARMC5. We found two variants. Five unrelated patients had identical variants (p.R619*). In two patients, the variant was found in offspring with the asymptomatic or presymptomatic state. Six of ten patients who tested positive for the ARMC5 pathogenic or likely pathogenic variant carried nonadrenal tumors; however, no loss of heterozygosity (LOH) or second hit of the ARMC5 gene was evident. The ARMC5 variant–positive group showed a significantly higher basal cortisol level. Furthermore, age-dependent cortisol hypersecretion was seen in the ARMC5 variant–positive group. Conclusions ARMC5 pathogenic variants are common (71%) in Japanese patients with PMAH. p.R619* might be a hot spot in Japanese patients with PMAH. Asymptomatic or presymptomatic pathogenic variant carriers were found among the family members of the patients. Although 50% of ARMC5 variant carriers had nonadrenal neoplastic lesions, no LOH or second hit of ARMC5 in the tumor tissues was evident. The ARMC5 variant–positive mutant group showed a higher basal cortisol level than the negative group.
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Bennett, Mark F., Michael S. Hildebrand, Sayaka Kayumi, Mark A. Corbett, Sachin Gupta, Zimeng Ye, Michael Krivanek et al. "Evidence for a Dual-Pathway, 2-Hit Genetic Model for Focal Cortical Dysplasia and Epilepsy". Neurology Genetics 8, n.º 1 (25 de enero de 2022): e0652. http://dx.doi.org/10.1212/nxg.0000000000000652.
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Background and ObjectivesThe 2-hit model of genetic disease is well established in cancer, yet has only recently been reported to cause brain malformations associated with epilepsy. Pathogenic germline and somatic variants in genes in the mechanistic target of rapamycin (mTOR) pathway have been implicated in several malformations of cortical development. We investigated the 2-hit model by performing genetic analysis and searching for germline and somatic variants in genes in the mTOR and related pathways.MethodsWe searched for germline and somatic pathogenic variants in 2 brothers with drug-resistant focal epilepsy and surgically resected focal cortical dysplasia (FCD) type IIA. Exome sequencing was performed on blood- and brain-derived DNA to identify pathogenic variants, which were validated by droplet digital PCR. In vitro functional assays of a somatic variant were performed.ResultsExome analysis revealed a novel, maternally inherited, germline pathogenic truncation variant (c.48delG; p.Ser17Alafs*70) in NPRL3 in both brothers. NPRL3 is a known FCD gene that encodes a negative regulator of the mTOR pathway. Somatic variant calling in brain-derived DNA from both brothers revealed a low allele fraction somatic variant (c.338C>T; p.Ala113Val) in the WNT2 gene in 1 brother, confirmed by droplet digital PCR. In vitro functional studies suggested a loss of WNT2 function as a consequence of this variant. A second somatic variant has not yet been found in the other brother.DiscussionWe identify a pathogenic germline mTOR pathway variant (NPRL3) and a somatic variant (WNT2) in the intersecting WNT signaling pathway, potentially implicating the WNT2 gene in FCD and supporting a dual-pathway 2-hit model. If confirmed in other cases, this would extend the 2-hit model to pathogenic variants in different genes in critical, intersecting pathways in a malformation of cortical development. Detection of low allele fraction somatic second hits is challenging but promises to unravel the molecular architecture of FCDs.
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Kumar, Anil, Rajni Sharma, Mohammed Faruq, Varun Suroliya, Manoj Kumar, Shilpa Sharma, Ralf Werner, Olaf Hiort y Vandana Jain. "Spectrum of Pathogenic Variants in SRD5A2 in Indian Children with 46,XY Disorders of Sex Development and Clinically Suspected Steroid 5α-Reductase 2 Deficiency". Sexual Development 13, n.º 5-6 (2019): 228–39. http://dx.doi.org/10.1159/000509812.
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The aim of this study was to assess the prevalence of pathogenic variants in the <i>SRD5A2</i> gene in children with 46,XY disorders of sex development (DSD) with normal to high serum testosterone levels and absence of Müllerian structures on imaging and to evaluate the genotype-phenotype correlation. Seventy-five patients with 46,XY DSD and probable clinical diagnosis of 5α-reductase 2 deficiency or androgen insensitivity syndrome were enrolled. Genetic analysis was done for pathogenic variants in <i>SRD5A2</i>, and the genotype-phenotype correlation was studied. As a result, 10 pathogenic or likely pathogenic biallelic variants in <i>SRD5A2, </i>either homozygous or compound heterozygous, were identified in 25 of 75 (33.3%) patients. The hCG stimulated testosterone: dihydrotestosterone (T:DHT) ratio was elevated in all patients with pathogenic variants in <i>SRD5A2</i> and in nearly 90% of those without pathogenic variants in <i>SRD5A2</i> in whom this was assessed. The missense pathogenic variant p.R246Q was a hotspot. One novel pathogenic variant p.Y178*, and a variant p.F194I, not previously reported in patients with 5α-reductase 2 deficiency, were identified. The missense variant p.F194I was predicted as deleterious and damaging by in silico analysis and as likely to reduce the enzyme activity by protein modeling. In conclusion, pathogenic variants in <i>SRD5A2 </i>can be detected in a wide spectrum of Indian patients with 46,XY DSD. Molecular genetic analysis should be considered as a first-line test as the T:DHT ratio lacks specificity and a hotspot variant is present in a vast majority.
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Kumar, Anil, Rajni Sharma, Mohammed Faruq, Manoj Kumar, Shilpa Sharma, Ralf Werner, Olaf Hiort y Jain Vandana. "Clinical, Biochemical, and Molecular Characterization of Indian Children with Clinically Suspected Androgen Insensitivity Syndrome". Sexual Development 16, n.º 1 (22 de octubre de 2021): 34–45. http://dx.doi.org/10.1159/000519047.
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This study describes the clinical, biochemical, and molecular characteristics of Indian children with 46,XY DSD and suspected androgen insensitivity syndrome (AIS). Fifty children (median age 3.0 years, range 0–16.5 years) with 46,XY DSD and a suspected diagnosis of AIS were enrolled. Sanger sequencing was performed to identify pathogenic variants in the androgen receptor (<i>AR</i>) gene and to study genotype-phenotype correlations. All 5 (100%) patients with CAIS and 14/45 (31%) patients with PAIS had pathogenic/likely pathogenic variants in the <i>AR</i> gene (overall, 14 different variants in 19 patients; 38.8%). There was no significant difference in clinical (cryptorchidism, hypospadias, or external masculinizing score) or biochemical parameters (gonadotropins and testosterone) between patients with or without pathogenic variants. However, patients with AIS were more likely to have a positive family history, be assigned female gender at birth, and present with gynaecomastia at puberty. Three novel pathogenic/likely pathogenic variants, including one splice donor site variant c.2318+1G>A, one frameshift variant p.H790Lfs*40, and one missense variant p.G821E, were identified in 3 patients with CAIS. The missense variant p.G821E was predicted as deleterious, damaging, disease-causing, and likely functionally inactive by in silico analysis and protein modelling study. Two previously not reported pathogenic/likely pathogenic variants, including p.R386H and p.G396R, were identified in patients with PAIS. This study contributes in expanding the spectrum of pathogenic variants in the <i>AR</i> gene in patients with AIS. Only 31% patients with a provisional diagnosis of PAIS had pathogenic variants in the <i>AR</i> gene, suggesting other possible mechanisms or candidate genes may be responsible for such a phenotypic presentation.
Tesis sobre el tema "Pathogenic variant"
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Röhrs, Susanne. "A neuraminidase-negative variant of highly pathogenic avian influenza virus H5N1". Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-177974.
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Hochpathogene Aviäre Influenzaviren (HPAIV) des Subtypes H5N1 zirkulieren seit den ersten Ausbrüchen vor mehr als 10 Jahren in Wirtschaftsgeflügel und Wildvögeln, vor allem in Asien und Afrika. Vakzinekampagnien mit ungeeigneten oder unwirksamen Impfstoffen sowie Transporte von infiziertem Geflügel, sowie Wildvogelzüge führten nicht nur zur Verbreitung der Viren, sondern auch zu Reassortierungen mit anderen zirkulierenden Influenzaviren und zur antigenetischen Drift. Bis heute ist kein Impfstoff verfügbar der ausreichenden und schnellen Schutz vor einer HPAIV H5N1 Infektion, sowie der Ausscheidung bietet, genauso wie eine einfache Applikation ermöglicht und sowohl im Säugetier, als auch Vogel einsetzbar ist. Im Falle eines Ausbruches wäre eine solche Vaccine das perfekte Werkzeug, um eine Pandemie zu verhindern.
Die in dieser Dissertation vorgestellten Arbeiten zeigen die in-vitro und in-vivo Charakterisierung und einer Neuraminidase-negativen H5N1 Mutante, so wie den Einsatz als Impfstoffmodel zur Untersuchung der Frühimmunisierung.
Ein hochpathogenes H5N1 Isolat des Stammes 2.1 (A/swan/Germany/R65/2006) wurde fünfzigmal im embryonierten Hühnerei passagiert. Den Passagen wurde bei jedem Durchgang polybasisches Hühnerserum mit Antikörper gegen H5 und N2 beigemischt, um einen selektiven Druck auf das Virus zu erzeugen. Die daraus resultierende Mutante zeigte überaschenderweise nicht die erwarteten Veränderungen und Anpassungen im Haemagglutinin, sondern Deletionen und „Segment-shuffling“ im Segment 6, welches für das Neuraminidaseprotein kodiert. Des Weiteren konnte keine Neuraminidaseaktivität mehr nachgewiesen werden.
Die Deletionen führten zu Veränderungen im Wachstumsverhalten des Virus und der Pathogenität im Tier. So konnte hier gezeigt werden, dass die Mutante ohne Zugabe von externer Neuraminidase oder Adaptation des Haemagglutinins in Zellkultur und Ei hohe Infektionstiter erreichen kann. Im Vergleich zum Ursprungsvirus aber Wachstumsdefizite aufweist, die sich in kleineren Plaques und langsamerem Wachstum auf Zellkultur zeigen.
Infektionsversuche im Huhn zeigten, dass das Virus weder Klinik auslöst, noch ausgeschieden oder übertragen wird, aber eine gute Immunantwort induziert. Hohe Antikörper konnten nur erreicht werden, wenn Hühner intramuskulär infiziert wurden, wohingegen eine Applikation über den oronasalen Weg nicht bei allen Tieren gelang.
Die gute Immunantwort und Apathogenität des Virus machten es im weiteren Verlauf zu einem geeigneten Kandidaten für Frühimmunisierungsversuche im Säugetier- und Vogelmodell. So wurden Balb/C Mäuse, Frettchen und Hühner ein, drei und sieben Tage vor einer H5N1 Belastungsinfektion mit der H5N1 Mutante intramuskulär oder intranasal immunisiert. Dabei konnte ein 100% Schutz vor klinischen Symptomen und der Ausscheidung des Challenge-Virus nach nur 7 Tagen gezeigt werden. Darüber hinaus waren die Tiere vor Klinik bereits drei Tage nach der Immunisierung geschützt, wobei aber virale RNA in oronasalen Proben und auch den Organen nachgewiesen werden konnte.
Die Neuraminidasedeletion der Mutante ermöglichte außerdem eine Unterscheidung von immunisierten zu infizierten Tieren, da erstere im ELISA NP- aber keine NA-Antikörper zeigten, wohingegen infizierte Tiere Antikörper gegen beide Proteine bildeten.
In Zukunft könnten NA negative Influenzaviren zusätzlich oder als Alternative zu den gängigen stamping out Strategien eingesetzt werden. Dafür aber sind weiter Untersuchungen essentiell. Die hochpathogene Spaltstelle im HA von „EscEgg50A“ impliziert das Risiko mit zirkulierenden AI Stämmen zu reassortieren und ist daher für den Einsatz zum Beispiel in Zuchtherden ungeeignet. Darüber hinaus ist das Wissen über das NA Protein und seine Funktionsweise sehr lückenhaft und NA-negative Mutanten könnten für zukünftige Untersuchungen genutzt werden.
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CICCARESE, GIULIA. "GENOTYPE – PHENOTYPE CORRELATIONS IN CUTANEOUS MELANOMA PATIENTS CARRIER OF THE MITF p.E318K PATHOGENIC VARIANT". Doctoral thesis, Università degli studi di Genova, 2019. http://hdl.handle.net/11567/945094.
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Background: The p.E318K variant of the microphthalmia-associated transcription factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined. The purpose of our study was to assess the association between the p.E318K germline variant and clinic-phenotypical features of MITF+ compared to non-carriers (MITF-), including dermoscopic findings of melanomas and dysplastic nevi.
Methods: we retrospectively analyzed a consecutive series of 1386 patients recruited between 2000 and 2017 who underwent genetic testing for CDKN2A, CDK4, MC1R and MITF germline variants in our laboratory for diagnostic/research purposes. The patients were probands of melanoma-prone families and apparently sporadic single or multiple primary melanoma patients. For all, we collected clinical, pathological information and dermoscopic images of the histopathologically diagnosed melanomas and dysplastic nevi, when available.
Results: After excluding patients positive for CDKN2A/CDK4 pathogenic variants and those affected by non-cutaneous melanomas, our study cohort comprised 984 cutaneous melanoma patients, 22 MITF+ and 962 MITF-. MITF+ were more likely to develop dysplastic nevi and multiple primary melanomas. Nodular melanoma was more common in MITF+ patients (32% compared to 19% in MITF-). MITF+ patients showed more frequently dysplastic nevi and melanomas with uncommon dermoscopic patterns (unspecific), as opposed to MITF- patients, whose most prevalent pattern was the multicomponent.
Conclusions: MITF+ patients tend to develop melanomas and dysplastic nevi with histopathological features, frequency and dermoscopic patterns often different from those prevalent in MITF- patients. Our results emphasize the importance of melanoma prevention programs for MITF+ patients, including dermatologic surveillance with digital follow-up.
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Almanza, Deanna J. "Medical Decision Making among Individuals with a Variant of Uncertain Significance in a Hereditary Cancer Gene and those with a CHEK2 Pathogenic Variant". Scholar Commons, 2019. https://scholarcommons.usf.edu/etd/7726.
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Despite national guidelines, women with a BRCA VUS or CHEK2 pathogenic variant are choosing to have risk-reducing surgeries such as bilateral mastectomies which are not aligned with their level of cancer risk based on genetic test results alone. Semi-structured telephone interviews were conducted with 6 women with a BRCA VUS and 12 with a CHEK2 pathogenic variant exploring the factors influencing their decision-making process when considering medical management options. Patients from a cancer registry agreed to a recorded telephone interview. Coding was performed using the main constructs from the Ottawa Patient Decision Guide including: knowledge, uncertainty, values, and support. Iterative analysis was used to identify emerging themes.
Analysis of the interviews revealed overlapping of the four constructs in the decision-making process. The knowledge sought to make medical management decisions was driven by the uncertainty associated with the genetic test results. Participants often contextualized their risk by building on the risk associated with genetic test results with family history, variant re-interpretation, and the knowledge that the risks associated with other genes may be higher. Patients generally made the decision they thought was best for them, even though it was more difficult if that decision was not supported by healthcare providers, friends, or family. When faced with uncertain cancer risks and presented with options for medical management, values were weighed against the negatives of each option. Often mental health was prioritized over the negatives associated with ‘removing body parts’.
These findings offer a look into the decisional needs of patients such as accurate knowledge, certainty, decisional support, and attention to personal values. Better understanding of the unmet needs of these patients and working to rectify them through provider education, outreach, counseling strategies to mitigate uncertainty, and research on how to best address and identify each patient’s specific decisional needs can contribute to the goal of risk-appropriate and values-based decision-making. With a better understanding of patients’ decisional needs, healthcare providers can better advocate for tailored counseling sessions which explore and address specific patient needs to help them make informed, risk-appropriate, and value-based medical management decisions.
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Mondal, Shankar Prosad. "Molecular characterization of the features of antigenic and pathogenic variant strains of infectious bronchitis virus /". For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2005. http://uclibs.org/PID/11984.
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Darmawan, Hariyanto. "Transport of a pathogenic bacterium and its non-pathogenic variant strain through a granular porous medium: from a simple system to a real system". Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104768.
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The attachment efficiency of two strains of Escherichia coli O157:H7 – one pathogenic strain and another non-pathogenic strain – was measured over a range of solution ionic strengths and in two different granular systems: a simple system made of clean quartz sand and a real system made of natural subsurface soil. In this study, the relevance of the non-pathogenic strain of E. coli O157:H7 as a potential surrogate for its pathogenic counterpart was investigated. The results suggest that it is not straightforward to find an appropriate surrogate for the pathogenic strain. Different porous media begets different attachment efficiency of the potential surrogate strain relative to the attachment efficiency of the toxigenic strain. A modest attempt was also made to build an artificial system that mimics the natural soil, by coating the clean granular sand with humic acids and adding clay component.Pour étudier la contamination d'eaux souterraines, l'efficacité d'adhésion de deux variétés d'E. coli O157:H7 – une pathogène et une autre non-pathogène – a été mesurée sur une gamme de force ionique dans deux systèmes granulaires : un système simple fait de sable de quartz propre et un système naturel de sol souterrain. Dans cette étude, la pertinence de la variété non-pathogène (E. coli O157:H7) comme substitut potentiel pour sa contrepartie fut étudiée. Les résultats suggèrent qu'il est très difficile de trouver un substitut approprié de la variété pathogène pour ce type d'études, car différents médias porreaux engendrent différentes efficacités d'adhésion de la variété substitut potentielle. Une tentative a aussi été faite de construire un système artificiel dans le labo qui imite le sol naturel, en enrobant le sable de quartz avec des acides humiques et par l'addition d'un composé d'argile.
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Al-Saadi, Abdulwahid. "Phenotypic characterization and sequence analysis of pthA homologs from five pathogenic variant groups of Xanthomonas citri". [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0011580.
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Kvist, Alexander. "Identifying Pathogenic Amino Acid Substitutions in Human Proteins Using Deep Learning". Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-233513.
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Many diseases of genetic origin originate from non-synonymous single nucleotide polymorphisms (nsSNPs). These cause changes in the final protein product encoded by a gene. Through large scale sequencing and population studies, there is growing availability of information of which variations are tolerated and which are not. Variant effect predictors use a wide range of information about such variations to predict their effect, often focusing on evolutionary information. Here, a novel amino acid substitution variant effect predictor is developed. The predictor is a deep convolutional neural network incorporating evolutionary information, sequence information, as well as structural information, to predict both the pathogenicity as well as the severity of amino acid substitutions. The model achieves state-of-the-art performance on benchmark datasets.
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HASSAN, AMAL. "FROM PROTEIN STRUCTURE TO DRUG DESIGN (DISCOVERY): TARGETING THE ION CHANNEL ASIC1 AND A PATHOGENIC VARIANT OF HUMAN GELSOLIN". Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/629877.
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La conoscenza della struttura tridimensionale di un potenziale target farmacologico apre la via a nuove strategie terapeutiche (ad esempio tramite structure-based drug design (SBDD)) ed è requisito fondamentale per la bioinformatica strutturale.
In questo contesto, durante la mia tesi di dottorato, sono state studiate due proteine di interesse biomedico. La prima è una proteina di membrana, l’isoforma 1 dell’Acid Sensing Ion Channel (ASIC), implicata in diverse malattie neurodegenerative. In studi precedenti il diminazene aceturato (DA) si era dimostrato un potente inibitore del canale. Diversi analoghi di DA sono stati progettati su base strutturale e la loro affinità per ASIC analizzata tramite docking molecolare. Le molecole migliori sono state testate in saggi cellulari per valutarne l’efficacia. Per caratterizzare la capacità inibitoria degli analoghi sintetizzati in vitro, è stato messo a punto un protocollo per la produzione della proteina ASIC1, utilizzando diversi sistemi di espressione eterologa. La purificazione della proteina è stata effettuata usando un approccio high-throughput per supportare successivamente la cristallizzazione della proteina, al fine di ottenere informazioni più dettagliate sul meccanismo d’azione degli analoghi del DA e, di conseguenza, disegnare nuovi farmaci, isoforma-selettivi e in grado di attraversare la barriera emato-encefalica.
In secondo luogo, ho studiato la proteina Gelsolin (GSN), responsabile di una malattia familiare degenerativa (detta amiloidosi AGel). Lo scopo di questo progetto era quello di investigare l'effetto della mutazione D187N sulla struttura di GSN e la sua propensione ad aggregare e/o degradarsi in maniera anomala. Il D187N GSN è stato il primo mutante ad essere identificato, ma, ad oggi, non si avevano informazioni sulla sua struttura. In uno studio precedente, era stato identificato un nanobody (Nb11) in grado di proteggere la proteina dalla degradazione, ma il meccanismo di protezione non era stato chiarito. Nel mio lavoro ho risolto la struttura del complesso Nb11:D187N a 1.9 Å, permettendo la caratterizzazione molecolare del meccanismo di azione del Nb11. I dati strutturali ottenuti sono stati completati con una caratterizzazione biofisica e biochimica, estesa anche ad altre due varianti patologiche della GSN, recentemente identificate (G167R e N184K).Knowledge of the three-dimensional structure of therapeutically relevant proteins paves the way for novel strategies in pharmacological research (such as the structure-based drug design (SBDD) method) and establishes the foundations for structural bioinformatics. In this context, during my PhD Thesis, two therapeutically relevant proteins have been studied. First, a membrane protein, Acid Sensing Ion Channel (ASIC) isoform 1, a validated target in neurodegenerative disorders, was selected. Previous studies showed that diminazene aceturate (DA) is a potent small-molecule inhibitor of ASIC channels. Here, several DA analogues were screened by molecular docking and the best binders were tested in cell-based assays to further assess their efficacy. In order to determine the inhibitory capability of the synthesized analogues in vitro on the purified protein, the expression of ASIC1 was undertaken, using different organisms of expression. The protein purification was performed in a high-throughput approach in order to recover enough protein for crystallization, with the final aim of studying the mechanism of action of DA analogs, and support the design of new, isoform-selective and brain-penetrant drugs. Secondly, the soluble protein Gelsolin (GSN), responsible for a familial degenerative disease (AGel amyloidosis) was studied. Aim of this project was to understand the impact of the D187N mutation on GSN structure and its propensity to aberrant aggregation and/or degradation. D187N GSN mutant was the first identified in man, but its crystal structure had until now eluded any characterization. Conversely, a nanobody (Nb11) was shown to protect GSN from aberrant proteolysis, but its mechanism of protection remained unclear. Here, the structure of the Nb11:D187N complex was solved at 1.9 Å resolution, enabling the characterization of the Nb11action mechanism. The structural data were complemented with biophysical and biochemical characterisations. These studies were then extended to two recently identified pathological variants of GSN (G167R and N184K).
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Röhrs, Susanne [Verfasser] y Gerd [Akademischer Betreuer] Sutter. "A neuraminidase-negative variant of highly pathogenic avian influenza virus H5N1 : generation, characterization and use as a model for early onset of immunity / Susanne Röhrs. Betreuer: Gerd Sutter". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/1065610890/34.
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Bryen, Samantha Jane. "Identification and molecular mechanisms of pathogenic splicing variants in neuromuscular disorders". Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/26955.
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Background
For families with rare Mendelian disorders, obtaining a precise genetic diagnosis is essential to enable personalised and preventative medicine. However, only ∼50% of families receive a genetic diagnosis following genetic testing, as there are still many challenges in the clinical interpretation of genetic variation. One such challenge is the identification and classification of variants that disrupt precursor messenger RNA (pre-mRNA) splicing, hereafter termed splicing variants. Even though splicing variants are well recognised as a common cause of Mendelian disorders, they are regularly classified as Variants of Uncertain Significance (VUS) rendering them clinically unactionable. It is our inability to accurately predict if and how a variant disrupts pre-mRNA splicing that prevents definitive classification of putative splicing variants.
Aims
To explore the molecular mechanisms by which variants disrupt pre-mRNA splicing, thereby improving our ability to detect and accurately assign pathogenicity to splicing variants in the context of genetically diagnosing individuals with neuromuscular disorders.
Methods
We have a cohort of 214 families with neuromuscular disorders for whom we have iteratively applied exomic, genomic and transcriptomic diagnostic sequencing approaches. Putative splicing variants were identified within this cohort or referred to us as VUSs from collaborators. Functional studies were performed to assess variant effect on pre-mRNA splicing. Analysis of datasets derived from variant databases and the human reference genome provided additional insights.
Results
Numerous complex splicing variants were investigated and established as pathogenic for a variety of neuromuscular conditions. Splicing variants analysed included intronic deletions, deep intronic variants, coding variants, structural rearrangements, and extended splice site variants. The mechanistic basis of aberrant pre-mRNA splicing arising from these variants were explored, revealing novel or under-recognised disease mechanisms.
Conclusions
We reveal important mechanistic insights behind pre-mRNA splicing that can be incorporated into diagnostic pipelines and used to inform new splicing prediction algorithms. The discoveries and lessons learned within this thesis are applicable to all rare Mendelian disorders and cancer genomics.
Libros sobre el tema "Pathogenic variant"
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Syrris, Petros y Alexandros Protonotarios. Arrhythmogenic right ventricular cardiomyopathy: genetics. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0359.
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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of the heart muscle which is typically inherited in an autosomal dominant manner. It is believed to be familial in over 50% of cases. A recessive mode of inheritance has also been reported in syndromic cases with cardiocutaneous features. The classic form of the disorder is considered to be ‘a disease of the desmosome’ as pathogenic variants have been identified in five genes encoding key desmosomal proteins: plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. Mutations in these genes account for 30–50% of ARVC cases. A further eight non-desmosomal genes have also been implicated in the pathogenesis of the disorder but only account for rare cases. Studies of patients with ARVC-associated gene mutations have revealed marked genetic heterogeneity and very limited genotype–phenotype correlation. Disease expression often varies significantly amongst individuals carrying the same mutation. It has been proposed that the presence of more than one sequence variant is required to determine overt clinical disease and patients with multiple variants have a more severe phenotype compared to single variant carriers. Identification of a potentially pathogenic variant comprises a major criterion in the diagnosis of ARVC but informative integration of genetic testing into clinical practice remains challenging. Gene testing should be used to identify asymptomatic family members at risk and only aids diagnosis in cases of high suspicion for ARVC, along with other evident features of the disease already present. However, genetic findings should be used with caution in clinical practice and their interpretation must be performed in expert centres.
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McKinlay Gardner, R. J. y David J. Amor. Normal Chromosomal Variation. Editado por R. J. McKinlay Gardner y David J. Amor. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199329007.003.0017.
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Knowing what is normal and what is not is becoming a particular challenge in this era of molecular karyotyping. This chapter reviews the normal chromosome variation from classical times, now very well understood. This is followed by a discussion of the complexity and uncertainty that the molecular approach has, in this century, challenged researchers with. In particular, the chapter discusses the concept of the copy number variant (CNV) and how the harmlessness, or not, of a CNV may be assessed. Mention is made of CNVs potentially acting as “second hits,” such that, while nonpathogenic in one setting, they may contribute to an abnormal phenotype in the context of another, independent chromosome abnormality or CNV. The “sliding scale” of interpretation from “known pathogenic” through “known benign” Is noted. The chapter refers to useful databases to which the counselor may have access.
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Merriman, Tony R. The genetic basis of gout. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0040.
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An individual’s risk of gout is determined by a complex relationship between inherited genetic variants and environmental exposures. Genetic variants that control hyperuricaemia and subsequent progression to clinical gout specify pathogenic pathways that could be therapeutically targeted. Genome-wide association studies (GWAS) have provided novel insights into the pathways leading to hyperuricaemia. GWAS have identified the renal uric acid transporter SLC2A9/GLUT9 and the gut excretory molecule ABCG2, which each have very strong genetic effects in the control of urate levels and risk of gout. Histone deacetylase inhibitors are able to correct the genetically-determined ABCG2 dysfunction. Other renal uric acid transporters, such as SLC22A11/OAT4 and SLC22A12/URAT1 have been confirmed to be genetically associated with urate and the risk of gout. Genes that generate urate during glycolysis (e.g. GCKR) are also implicated. In contrast very little is known about genetic variants that control the progression from hyperuricaemia to gout with the toll-like receptor 4 gene being the only gene with replicated evidence of association.
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Gleń-Karolczyk, Katarzyna. Zabiegi ochronne kształtujące plonowanie zdrowotność oraz różnorodność mikroorganizmów związanych z czernieniem pierścieniowym korzeni chrzanu (Atmoracia rusticana Gaertn.). Publishing House of the University of Agriculture in Krakow, 2019. http://dx.doi.org/10.15576/978-83-66602-39-7.
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Horseradish roots, due to the content of many valuable nutrients and substances with healing and pro-health properties, are used more and more in medicine, food industry and cosmetics. In Poland, the cultivation of horseradish is considered minor crops. In addition, its limited size causes horseradish producers to encounter a number of unresolved agrotechnical problems. Infectious diseases developing on the leaves and roots during the long growing season reduce the size and quality of root crops. The small range of protection products intended for use in the cultivation of horseradish generates further serious environmental problems (immunization of pathogens, low effectiveness, deterioration of the quality of raw materials intended for industry, destruction of beneficial organisms and biodiversity). In order to meet the problems encountered by horseradish producers and taking into account the lack of data on: yielding, occurrence of infectious diseases and the possibility of combating them with methods alternative to chemical ones in the years 2012–2015, rigorous experiments have been carried out. The paper compares the impact of chemical protection and its reduced variants with biological protection on: total yield of horseradish roots and its structure. The intensification of infectious diseases on horseradish leaves and roots was analyzed extensively. Correlations were examined between individual disease entities and total yield and separated root fractions. A very important and innovative part of the work was to learn about the microbial communities involved in the epidemiology of Verticillium wilt of horseradish roots. The effect was examined of treatment of horseradish cuttings with a biological preparation (Pythium oligandrum), a chemical preparation (thiophanate-methyl), and the Kelpak SL biostimulator (auxins and cytokinins from the Ecklonia maxima algae) on the quantitative and qualitative changes occurring in the communities of these microorganisms. The affiliation of species to groups of frequencies was arranged hierarchically, and the biodiversity of these communities was expressed by the following indicators: Simpson index, Shannon–Wiener index, Shannon evenness index and species richness index. Correlations were assessed between the number of communities, indicators of their biodiversity and intensification of Verticillium wilt of horseradish roots. It was shown that the total yield of horseradish roots was on average 126 dt · ha–1. Within its structure, the main root was 56%, whereas the fraction of lateral roots (cuttings) with a length of more than 20 cm accounted for 26%, and those shorter than 20 cm for 12%, with unprofitable yield (waste) of 6%. In the years with higher humidity, the total root yield was higher than in the dry seasons by around 51 dt · ha–1 on average. On the other hand, the applied protection treatments significantly increased the total yield of horseradish roots from 4,6 to 45,3 dt · ha–1 and the share of fractions of more than 30 cm therein. Higher yielding effects were obtained in variants with a reduced amount of foliar application of fungicides at the expense of introducing biopreparations and biostimulators (R1, R2, R3) and in chemical protection (Ch) than in biological protection (B1, B2) and with the limitation of treatments only to the treatment of cuttings. The largest increments can be expected after treating the seedlings with Topsin M 500 SC and spraying the leaves: 1 × Amistar Opti 480 SC, 1 × Polyversum WP, 1 × Timorex Gold 24 EC and three times with biostimulators (2 × Kelpak SL + 1 × Tytanit). In the perspective of the increasing water deficit, among the biological protection methods, the (B2) variant with the treatment of seedlings with auxins and cytokinins contained in the E. maxima algae extract is more recommended than (B1) involving the use of P. oligandrum spores. White rust was the biggest threat on horseradish plantations, whereas the following occurred to a lesser extent: Phoma leaf spot, Cylindrosporium disease, Alternaria black spot and Verticillium wilt. In turn, on the surface of the roots it was dry root rot and inside – Verticillium wilt of horseradish roots. The best health of the leaves and roots was ensured by full chemical protection (cuttings treatment + 6 foliar applications). A similar effect of protection against Albugo candida and Pyrenopeziza brassicae was achieved in the case of reduced chemical protection to one foliar treatment with synthetic fungicide, two treatments with biological preparations (Polyversum WP and Timorex Gold 24 EC) and three treatments with biostimulators (2 × Kelpak SL, 1 × Tytanit). On the other hand, the level of limitation of root diseases comparable with chemical protection was ensured by its reduced variants R3 and R2, and in the case of dry root rot, also both variants of biological protection. In the dry years, over 60% of the roots showed symptoms of Verticillium wilt, and its main culprits are Verticillium dahliae (37.4%), Globisporangium irregulare (7.2%), Ilyonectria destructans (7.0%), Fusarium acuminatum (6.7%), Rhizoctonia solani (6.0%), Epicoccum nigrum (5.4%), Alternaria brassicae (5.17%). The Kelpak SL biostimulator and the Polyversum WP biological preparation contributed to the increased biodiversity of microbial communities associated with Verticillium wilt of horseradish roots. In turn, along with its increase, the intensification of the disease symptoms decreased. There was a significant correlation between the richness of species in the communities of microbial isolates and the intensification of Verticillium wilt of horseradish roots. Each additional species of microorganism contributed to the reduction of disease intensification by 1,19%.
Capítulos de libros sobre el tema "Pathogenic variant"
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Aguti, Sara, Fady Guirguis, Carsten Bönnemann, Francesco Muntoni, Véronique Bolduc y Haiyan Zhou. "Exon-Skipping for a Pathogenic COL6A1 Variant in Ullrich Congenital Muscular Dystrophy". En Methods in Molecular Biology, 387–407. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2772-3_20.
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Lamontagne, L. y J. M. Dupuy. "Characterization of a Non-Pathogenic MHV3 Variant Derived from a Persistently Infected Lymphoid Cell Line". En Coronaviruses, 255–63. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4684-1280-2_30.
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Proctor, Richard A. "Microbial Pathogenic Factors: Small-Colony Variants". En Infections Associated with Indwelling Medical Devices, 41–54. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555818067.ch3.
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Velaga, Ravi, Masakazu Toi, Nobuko Kawaguchi-Sakita, John R. Benson y Noriko Senda. "Hereditary Breast Cancer and Pathogenic Germline Variants". En Screening and Risk Reduction Strategies for Breast Cancer, 45–59. Singapore: Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-19-7630-8_3.
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Proctor, Richard A. "Respiration and Small-Colony Variants of Staphylococcus aureus". En Gram-Positive Pathogens, 434–42. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555816513.ch35.
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Proctor, Richard. "Respiration and Small Colony Variants of Staphylococcus aureus". En Gram-Positive Pathogens, 549–61. Washington, DC, USA: ASM Press, 2019. http://dx.doi.org/10.1128/9781683670131.ch34.
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Kolc, Kristy L., Rikke S. Møller, Lynette G. Sadleir, Ingrid E. Scheffer, Raman Kumar y Jozef Gecz. "PCDH19 Pathogenic Variants in Males: Expanding the Phenotypic Spectrum". En Cell Biology and Translational Medicine, Volume 10, 177–87. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/5584_2020_574.
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Neil, J. C., R. Fulton, M. Rigby y M. Stewart. "Feline Leukaemia Virus: Generation of Pathogenic and Oncogenic Variants". En Current Topics in Microbiology and Immunology, 67–93. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-76524-7_4.
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Fleming, J. O., M. D. Trousdale, S. A. Stohlman y L. P. Weiner. "Pathogenic Characteristics of Neutralization-Resistant Variants of JHM Coronavirus (MHV-4)". En Coronaviruses, 333–42. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4684-1280-2_42.
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Proctor, Richard A., Donna M. Bates y Peter J. McNamara. "Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens". En Emerging Infections 5, 95–110. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555816988.ch6.
Texto completoActas de conferencias sobre el tema "Pathogenic variant"
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Goveia, Rebeca Mota, Paula Francinete Faustino Silva, Thais Bomfim Teixeira, Isabela Gasparini Arraes, Ruffo Freitas-Júnior y Elisângela Paula Silveira Lacerda. "ANALYSIS OF PATHOGENIC AND UNCERTAIN SIGNIFICANCE VARIANTS IN NINE GENES OF THE BRCA1-MEDIATED HOMOLOGOUS RECOMBINATION PATHWAY IN PATIENTS WITH SUSPECTED HEREDITARY BREAST AND OVARIAN CANCER SYNDROME IN CENTRAL BRAZIL." En Scientifc papers of XXIII Brazilian Breast Congress - 2021. Mastology, 2021. http://dx.doi.org/10.29289/259453942021v31s1038.
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Introduction: Breast cancer is the most frequent type of cancer in the world and the biggest cause of female deaths. About 10%–15% of cases are due to hereditary factors. The profile of genetic variants is still scarcely known among the Brazilian population and there are no published data for the central region of the country. Objectives: This study aimed to analyze the profile of pathogenic variants (PV) and of the ones of uncertain significance (VUS) for the RAD50, RAD51C, RAD51D, ATM, PALB2, BRIP1, BARD1 and CHEK2 genes in this population. Methods: 113 patients diagnosed with breast or ovarian cancer who met the National Comprehensive Cancer Networking criteria for hereditary breast and ovarian cancer syndrome were selected. The genes had all regions sequenced using NGS (New Generation Sequencing) and the raw data were evaluated using the Sophia DDM and IonReporter softwares. Results: A total of 3.53% of patients had PV in the PALB2 (c.2257C>T), BARD1 (c.176_177delAG), RAD50 (c.2165dupA) or ATM (c.7913G>A) genes. Patients with pathogenic variants in ATM and PALB2 genes were diagnosed before the age of 40. Patients with pathogenic variants in the BARD1 and RAD50 genes had triple negative breast cancer before the age of 60. The patient with a pathogenic variant in the RAD50 gene also developed ovarian cancer. It was observed that 24.77% of the patients had some VUS, 35.29% of which were in the ATM gene, and a new VUS in the CHEK2 gene (c.1151T>C), related to male breast cancer. Conclusions: These findings contribute to a better understanding of the phenotype of patients with pathogenic variants related to breast cancer in non-BRCA genes. In addition, it reveals a new pathogenic variant in the CHEK2 gene, not described in the literature, related to a case of male breast cancer.
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Tanatar, Ayşe, Şerife Gül Karadağ, Hafize Emine Sonmez, Mustafa Çakan y Nuray Aktay Ayaz. "SAT0522 COMPARISON OF CHILDREN CARRYING E148Q VARIANT WITH CHILDREN CARRYING HOMOZYGOUS PATHOGENIC VARIANTS". En Annual European Congress of Rheumatology, EULAR 2019, Madrid, 12–15 June 2019. BMJ Publishing Group Ltd and European League Against Rheumatism, 2019. http://dx.doi.org/10.1136/annrheumdis-2019-eular.7098.
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Xian, W., W. Rao y F. Mckeon. "Variant and Potentially Pathogenic Stem Cells in COPD Lung". En American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a4548.
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Braga, Vinícius Lopes, Wladimir Bocca Vieira de Rezende Pinto, Bruno de Mattos Lombardi Badia, José Marcos Vieira de Albuquerque Filho, Igor Braga Farias, Paulo Victor Sgobbi de Souza y Acary Souza Bulle Oliveira. "Spastic paraplegia type 73: expanding phenotype of the first two Brazilian families". En XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.552.
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Context: Hereditary spastic paraplegias (HSPs) represent an expanding group of neurodegenerative diseases characterized mainly by progressive spastic paraparesis of the lower limbs. More than 80 different genetic loci have been associated with HSPs. In 2015, heterozygous pathogenic variants in the CPT1C gene were first associated with SPG73, not yet described in Brazilian patients. Objective: We present clinical, neuroimaging and genetic features of three Brazilian patients with SPG73. Cases reports: We report one male and two female patients, age range 36 to 78 years old. Case 1 presented with a 4-year-history of spasticity, predominantly crural tetraplegia, bladder incontinence, dysphagia and dysphonia. Family history disclosed a sister with epilepsy. Whole-exome sequencing (WES) disclosed a heterozygosis variant c.863G>A (p.Arg288His) in exon 9 of the CPT1C. Cases 2 and 3 are first degree relatives (mother and son). Both presented with long-standing slowly progressive spastic paraplegia. Case 3 presented bladder incontinence, constipation, dysphagia and dysphonia at late stages. Cases 2 and 3 WES disclosed the heterozygosis variant c.196T>G (p.Phe66Val) in exon 4 of the CPT1C. Discussion: Previous literature described six patients from an Italian family with pure HSPs phenotype and the pathogenic variant c.109C>G (p.Arg3. 7Cys) in CPT1C gene. Another group described three patients associated with pure HSPs phenotype and the pathogenic variant (c.226C>T) in the CPT1C gene. All previous reported cases had benign clinical course and bulbar involvement was not described before. One of our cases presented with a de novo variant and rapidly progressive motor and bulbar compromise. Conclusion: our cases expand the current knowledge about SPG73, including a rapidly progressive phenotype with bulbar involvement and cognitive compromise at late stages of disease course.
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Klauser, Anna-Lena, Miriam Erlacher y Wibke G. Janzarik. "Pathogenic Compound-Heterozygous PARN Variant Mimicking Pontocerebellar Hypoplasia Type 2A". En Abstracts of the 46th Annual Meeting of the Society for Neuropediatrics. Georg Thieme Verlag KG, 2021. http://dx.doi.org/10.1055/s-0041-1739580.
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Brooks, Joseph Bruno Bidin. "De novo variant in the MAPK8IP3 gene in the differential diagnosis of global development delay. Case report." En XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.181.
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Context: The global development delay has a high prevalence and heterogeneity in the world population. With the advancement of technology and detection of pathogenic variants detected by sequencing the exome, genes related to global developmental delay could be identified and collaborate for further clinical clarification. Among the studied genes, the MAPK8IP3 gene, became an attractive candidate due to its performance in neuronal axonal transport in vertebrates and invertebrates. This case report was approved by the Ethics Committee of Universidade Metropolitana de Santos. Case Report: The present case refers to a 6-year-old male patient presenting with a clinical picture of global developmental delay without bodily dysmorphia. Cerebellar ataxia, muscle hypotonia and intellectual impairment are important clinical impairments. Skull MRI and complementary exams were normal. The genetic study showed a new and heterozygous pathogenic variant in the MAPK8IP3 gene. Conclusions: Symptomatic treatment with multiprofessional rehabilitation was instituted with partial improvement of symptoms.
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Reyes De Jesus, D., R. A. Mosquera y W. De Jesus-Rojas. "New Pathogenic RSPH4A Variant in a Child with Primary Ciliary Dyskinesia". En American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a3390.
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Hensen, F., V. C. Stark, D. Diaz-Gil, F. Kortüm, R. Kozlik-Feldmann, K. Kutsche, J. Olfe y T. S. Mir. "Genotype–Phenotype Correlations in Pediatric Patients with a Heterozygous Pathogenic FBN1 Variant". En The 54th Annual Meeting of the German Society for Pediatric Cardiology (DGPK). Georg Thieme Verlag KG, 2022. http://dx.doi.org/10.1055/s-0042-1742982.
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Iordache, Ovidiu, Elena-Cornelia Tănăsescu, Elena Perdum, Lucia Secareanu, Mihaela-Cristina Lite y Irina-Mariana Sandulache. "Antimicrobial Activity of FIR Functionalized Textile Materials against Pathogenic Fungi Strains". En The 9th International Conference on Advanced Materials and Systems. INCDTP - Leather and Footwear Research Institute (ICPI), Bucharest, Romania, 2022. http://dx.doi.org/10.24264/icams-2022.ii.10.
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Far infrared (FIR) functional textiles are a new category of functional textiles that have the potential to improve well-being and health. At the molecular level, FIR exerts strong rotational and vibrational effects with potential biological benefits. The majority of textiles with antimicrobial functionalization are based on synthetic products, and there is a need to link current end-user demands with both efficient products and low environmental impact, promoting natural antimicrobial treatments as viable solutions. Two structures of knitwear were obtained, with functional inorganic particles with antimicrobial, anti-UV and IR emission properties: variant 1: 100% BBC gauze ground yarn plated with functionalized polyamide yarn; variant 2: 85% wool/15% cashmere blend ground yarn plated with functionalized polyamide yarn. The antimicrobial efficiency of two types of functionalized materials was tested against six pathogenic microbial strains: Tricoderma viride (laboratory strain), Aspergillus flavus (laboratory strain), Candida albicans (ATCC 90028), Epidermophyton floccosum (CCM 8339), Trichophyton interdigitale (ATCC 9533) and Aspergillus niger (IMI 45551), highlighting various degrees of microbial reduction, depending on both the material and the tested strain, with lowest percentage microbial reduction of 9.67&, against Aspergillus niger strain, and highest of 86.65%, against Candida albicans.
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Albuquerque Filho, José Marcos Vieira de, Natália Merten Athayde, Alzira Alves de Siqueira Carvalho, Igor Braga Farias, Roberta Ismael Lacerda Machado y Marco Antônio Troccoli Chieia. "Familial ALS Type 25 – A Brazillian Case Serie". En XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.186.
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Introduction: Familial Amyotrophic Lateral Sclerosis (fALS) represent 5-10% of ALS patients. Different mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) cause Hereditary Spastic Paraplegia Type 10 (HSP10), Charcot-Marie-Tooth 2 (CMT2), Neonatal Intractable Myoclonus and more recently described fALS Type 25. Previous described phenotypes are very similar to the sporadic type, except from the long course of disease. Methods: We describe four Brazillian patients, under clinical follow-up on two Neuromuscular services with genetic diagnosis of fALS25. Results: Four diferent fALS25 are described. Two brothers and two unrelated patients, with distinct features, three males and one female, age range from 72 to 24; age of onset ranged from 62 to 22. The genetic mutations were the following: simple heterozygous pathogenic variant c.1651C>G (p. Leu551Val), simple heterozygous pathogenic variant c.2953G>A (p. Gly985Ser) and pathogenic variant c.484C>T (p.Arg162Trp); all of KIF5A gene (fALS25). Only one patient presented with similar phenoptype and age of onset as sporadic ALS (sALS), the two brothers presented the symptoms at the ages of 28 and 30, the female patient at 22. All patients still walk without assistence after the diagnosis. All patients showed classic superior and inferior motor neuron involvement signs, but one brother had a mild limb ataxia. The three younger patients had MRI with no specific findings, except from subtle cortical atrophy in one brother, and mild vermis and corpus callosum atrophy on the other brother. Only the female patient had negative familiar history. Conclusions: fALS25 should be suspected in patient with fALS and longer course disease. Mutations KIF5A gene must be remembered either in juvenile form of ALS.
Informes sobre el tema "Pathogenic variant"
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Jia, Ziqi, Jiang Wu, Jiaxin Li, Jiaqi Liu y Xiang Wang. Meta-analysis of breast cancer risk associated with established germline pathogenic variants in breast cancer-predisposition genes in population-based studies. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, febrero de 2021. http://dx.doi.org/10.37766/inplasy2021.2.0017.
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Brayton, Kelly A., Varda Shkap, Guy H. Palmer, Wendy C. Brown y Thea Molad. Control of Bovine Anaplasmosis: Protective Capacity of the MSP2 Allelic Repertoire. United States Department of Agriculture, enero de 2014. http://dx.doi.org/10.32747/2014.7699838.bard.
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Anaplasmosis is an arthropod-borne disease of cattle caused by the rickettsia Anaplasmamarginale and is an impediment to efficient production of healthy livestock in both Israel and the United States. Currently, the only effective vaccines are derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Consequently, development of a safe, effective vaccine is a high priority. Despite its drawbacks as a live, blood-based vaccine, the Israel vaccine strain protects against disease upon challenge with wild-type A. marginale in extensive experimental trials and during 50 years of deployment in Israel. Field studies in Australia and Argentina indicate that this protection is broadly effective. Thus, to identify antigens for development of a safe and effective recombinant vaccine, we have used a comparative genomics approach by sequencing the Israel vaccine strain and searching for shared surface antigens with sequenced wild-type U.S. strains. We have focused on Msp2, the immune-dominant but antigenically variable surface protein, based on shared structure among strains and demonstration that antibody from cattle immunized with the Israel vaccine strain binds Msp2 from the genetically and geographically distinct U.S. St. Maries strain, consistent with the ability to protect against St. Maries challenge. Importantly, we have defined the full repertoire of Msp2 simple variants encoded by the vaccine strain and hypothesize that a recombinant vaccine encoding this full repertoire will induce protection equivalent to that induced by the live vaccine strain. Any escape from immunity by generation of complex Msp2 variants is predicted to carry a severe fitness cost that prevents high-level bacteremia and disease— consistent with the type of protection induced by the live vaccine strain. We tested the hypothesis that the Msp2 simple variant repertoires in wild-type A. marginale strains are recognized by antibody from cattle immunized with the Israel vaccine strain and that immunization with the vaccine strain Msp2 repertoire can recapitulate the protection provided by the vaccine strain upon challenge with Israel and U.S. strains of A. marginale. Our findings demonstrate that a set of conserved outer membrane proteins are recognized by immune serum from A. centrale vaccinated animals but that this set of proteins does not include Msp2. These findings suggest that “subdominant” immunogens are required for vaccine induced protection.
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Dubcovsky, Jorge, Tzion Fahima y Ann Blechl. Molecular characterization and deployment of the high-temperature adult plant stripe rust resistance gene Yr36 from wheat. United States Department of Agriculture, noviembre de 2013. http://dx.doi.org/10.32747/2013.7699860.bard.
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Stripe rust, caused by Puccinia striiformis f. sp. tritici is one of the most destructive fungal diseases of wheat. Virulent races that appeared within the last decade caused drastic cuts in yields. The incorporation of genetic resistance against this pathogen is the most cost-effective and environmentally friendly solution to this problem. However, race specific seedling resistance genes provide only a temporary solution because fungal populations rapidly evolve to overcome this type of resistance. In contrast, high temperature adult plant (HTAP) resistance genes provide a broad spectrum resistance that is partial and more durable. The cloning of the first wheat HTAP stripe rust resistance gene Yr36 (Science 2009, 323:1357), funded by our previous (2007-2010) BARD grant, provided us for the first time with an entry point for understanding the mechanism of broad spectrum resistance. Two paralogous copies of this gene are tightly linked at the Yr36 locus (WKS1 and WKS2). The main objectives of the current study were to characterize the Yr36 (WKS) resistance mechanism and to identify and characterize alternative WKSgenes in wheat and wild relatives. We report here that the protein coded by Yr36, designated WKS1, that has a novel architecture with a functional kinase and a lipid binding START domain, is localized to chloroplast. Our results suggest that the presence of the START domain may affect the kinase activity. We have found that the WKS1 was over-expressed on leaf necrosis in wheat transgenic plants. When the isolated WKS1.1 splice variant transcript was transformed into susceptible wheat it conferred resistance to stripe rust, but the truncated variant WKS1.2 did not confer resistance. WKS1.1 and WKS1.2 showed different lipid binding profiling. WKS1.1 enters the chloroplast membrane, while WKS1.2 is only attached outside of the chloroplast membrane. The ascorbate peroxidase (APX) activity of the recombinant protein of TmtAPXwas found to be reduced by WKS1.1 protein in vitro. The WKS1.1 mature protein in the chloroplast is able to phosphorylate TmtAPXprotein in vivo. WKS1.1 induced cell death by suppressing APX activity and reducing the ability of the cell to detoxify reactive oxygen. The decrease of APX activity reduces the ability of the plant to detoxify the reactive H2O2 and is the possible mechanism underlying the accelerated cell death observed in the transgenic plants overexpressing WKS1.1 and in the regions surrounding a stripe rust infection in the wheat plants carrying the natural WKS1.1 gene. WKS2 is a nonfunctional paralog of WKS1 in wild emmer wheat, probably due to a retrotransposon insertion close to the alternative splicing site. In some other wild relatives of wheat, such as Aegilops comosa, there is only one copy of this gene, highly similar to WKS2, which is lucking the retrotransposon insertion. WKS2 gene present in wheat and WKS2-Ae from A. showed a different pattern of alternative splice variants, regardless of the presence of the retrotransposon insertion. Susceptible Bobwhite transformed with WKS2-Ae (without retrotansposon insertion in intron10), which derived from Aegilops comosaconferred resistance to stripe rust in wheat. The expression of WKS2-Ae in transgenic plants is up-regulated by temperature and pathogen infection. Combination of WKS1 and WKS2-Ae shows improved stripe rust resistance in WKS1×WKS2-Ae F1 hybrid plants. The obtained results show that WKS1 protein is accelerating programmed cell death observed in the regions surrounding a stripe rust infection in the wheat plants carrying the natural or transgenic WKS1 gene. Furthermore, characterization of the epistatic interactions of Yr36 and Yr18 demonstrated that these two genes have additive effects and can therefore be combined to increase partial resistance to this devastating pathogen of wheat. These achievements may have a broad impact on wheat breeding efforts attempting to protect wheat yields against one of the most devastating wheat pathogen.
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Wisniewski, Michael E., Samir Droby, John L. Norelli, Noa Sela y Elena Levin. Genetic and transcriptomic analysis of postharvest decay resistance in Malus sieversii and the characterization of pathogenicity effectors in Penicillium expansum. United States Department of Agriculture, enero de 2014. http://dx.doi.org/10.32747/2014.7600013.bard.
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Blue mold of apple caused by Penicilliumexpansumis a major postharvest disease. Selection for postharvest disease resistance in breeding programs has been ignored in favor of fruit quality traits such as size, color, taste, etc. The identification of postharvest disease resistance as a heritable trait would represent a significant accomplishment and has not been attempted in apple. Furthermore, insight into the biology of the pathogenicity of P. expansumin apple could provide new approaches to postharvest decay management. Hypothesis: Postharvest resistance of apple to P. expansumcan be mapped to specific genetic loci and significant quantitative-trait-loci (QTLs) can be identified that account for a major portion of the population variance. Susceptibility of apple fruit to P. expansumis dependent on the ability of the pathogen to produce LysM effectors that actively suppress primary and/or secondary resistance mechanisms in the fruit. Objectives: 1) Identify QTL(s) and molecular markers for blue mold resistance in GMAL4593 mapping population (‘Royal Gala’ X MalussieversiiPI613981), 2) Characterize the transcriptome of the host and pathogen (P. expansum) during the infection process 3) Determine the function of LysM genes in pathogenicity of P. expansum. Methods: A phenotypic evaluation of blue mold resistance in the GMAL4593 mapping population, conducted in several different years, will be used for QTL analysis (using MapQTL 6.0) to identify loci associated with blue mold resistance. Molecular markers will be developed for the resistance loci. Transcriptomic analysis by RNA-seq will be used to conduct a time course study of gene expression in resistant and susceptible apple GMAL4593 genotypes in response to P. expansum, as well as fungal responses to both genotypes. Candidate resistance genes identified in the transcriptomic study and or bioinformatic analysis will be positioned in the ‘Golden Delicious’ genome to identify markers that co-locate with the identified QTL(s). A functional analysis of LysM genes on pathogenicity will be conducted by eliminating or reducing the expression of individual effectors by heterologous recombination and silencing technologies. LysMeffector genes will also be expressed in a yeast expression system to study protein function. Expected Results: Identification of postharvest disease resistance QTLs and tightly-linked genetic markers. Increased knowledge of the role of effectors in blue mold pathogenic
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Splitter, Gary y Menachem Banai. Microarray Analysis of Brucella melitensis Pathogenesis. United States Department of Agriculture, 2006. http://dx.doi.org/10.32747/2006.7709884.bard.
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Original Objectives 1. To determine the Brucella genes that lead to chronic macrophage infection. 2. To identify Brucella genes that contribute to infection. 3. To confirm the importance of Brucella genes in macrophages and placental cells by mutational analysis. Background Brucella spp. is a Gram-negative facultative intracellular bacterium that infects ruminants causing abortion or birth of severely debilitated animals. Brucellosis continues in Israel, caused by B. melitensis despite an intensive eradication campaign. Problems with the Rev1 vaccine emphasize the need for a greater understanding of Brucella pathogenesis that could improve vaccine designs. Virulent Brucella has developed a successful strategy for survival in its host and transmission to other hosts. To invade the host, virulent Brucella establishes an intracellular niche within macrophages avoiding macrophage killing, ensuring its long-term survival. Then, to exit the host, Brucella uses placenta where it replicates to high numbers resulting in abortion. Also, Brucella traffics to the mammary gland where it is secreted in milk. Missing from our understanding of brucellosis is the surprisingly lillie basic information detailing the mechanisms that permit bacterial persistence in infected macrophages (chronic infection) and dissemination to other animals from infected placental cells and milk (acute infection). Microarray analysis is a powerful approach to determine global gene expression in bacteria. The close genomic similarities of Brucella species and our recent comparative genomic studies of Brucella species using our B. melitensis microarray, suqqests that the data obtained from studying B. melitensis 16M would enable understanding the pathogenicity of other Brucella organisms, particularly the diverse B. melitensis variants that confound Brucella eradication in Israel. Conclusions Results from our BARD studies have identified previously unknown mechanisms of Brucella melitensis pathogenesis- i.e., response to blue light, quorum sensing, second messenger signaling by cyclic di-GMP, the importance of genomic island 2 for lipopolysaccharide in the outer bacterial membrane, and the role of a TIR domain containing protein that mimics a host intracellular signaling molecule. Each one of these pathogenic mechanisms offers major steps in our understanding of Brucella pathogenesis. Strikingly, our molecular results have correlated well to the pathognomonic profile of the disease. We have shown that infected cattle do not elicit antibodies to the organisms at the onset of infection, in correlation to the stealth pathogenesis shown by a molecular approach. Moreover, our field studies have shown that Brucella exploit this time frame to transmit in nature by synchronizing their life cycle to the gestation cycle of their host succumbing to abortion in the last trimester of pregnancy that spreads massive numbers of organisms in the environment. Knowing the bacterial mechanisms that contribute to the virulence of Brucella in its host has initiated the agricultural opportunities for developing new vaccines and diagnostic assays as well as improving control and eradication campaigns based on herd management and linking diagnosis to the pregnancy status of the animals. Scientific and Agricultural Implications Our BARD funded studies have revealed important Brucella virulence mechanisms of pathogenesis. Our publication in Science has identified a highly novel concept where Brucella utilizes blue light to increase its virulence similar to some plant bacterial pathogens. Further, our studies have revealed bacterial second messengers that regulate virulence, quorum sensing mechanisms permitting bacteria to evaluate their environment, and a genomic island that controls synthesis of its lipopolysaccharide surface. Discussions are ongoing with a vaccine company for application of this genomic island knowledge in a Brucella vaccine by the U.S. lab. Also, our new technology of bioengineering bioluminescent Brucella has resulted in a spin-off application for diagnosis of Brucella infected animals by the Israeli lab by prioritizing bacterial diagnosis over serological diagnosis.
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Sela, Hanan, Eduard Akhunov y Brian J. Steffenson. Population genomics, linkage disequilibrium and association mapping of stripe rust resistance genes in wild emmer wheat, Triticum turgidum ssp. dicoccoides. United States Department of Agriculture, enero de 2014. http://dx.doi.org/10.32747/2014.7598170.bard.
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The primary goals of this project were: (1) development of a genetically characterized association panel of wild emmer for high resolution analysis of the genetic basis of complex traits; (2) characterization and mapping of genes and QTL for seedling and adult plant resistance to stripe rust in wild emmer populations; (3) characterization of LD patterns along wild emmer chromosomes; (4) elucidation of the multi-locus genetic structure of wild emmer populations and its correlation with geo-climatic variables at the collection sites. Introduction In recent years, Stripe (yellow) rust (Yr) caused by Pucciniastriiformis f. sp. tritici(PST) has become a major threat to wheat crops in many parts of the world. New races have overcome most of the known resistances. It is essential, therefore, that the search for new genes will continue, followed by their mapping by molecular markers and introgression into the elite varieties by marker-assisted selection (MAS). The reservoir of genes for disease and pest resistance in wild emmer wheat (Triticumdicoccoides) is an important resource that must be made available to wheat breeders. The majority of resistance genes that were introgressed so far in cultivated wheat are resistance (R) genes. These genes, though confering near-immunity from the seedling stage, are often overcome by the pathogen in a short period after being deployed over vast production areas. On the other hand, adult-plant resistance (APR) is usually more durable since it is, in many cases, polygenic and confers partial resistance that may put less selective pressure on the pathogen. In this project, we have screened a collection of 480 wild emmer accessions originating from Israel for APR and seedling resistance to PST. Seedling resistance was tested against one Israeli and 3 North American PST isolates. APR was tested on accessions that did not have seedling resistance. The APR screen was conducted in two fields in Israel and in one field in the USA over 3 years for a total of 11 replicates. We have found about 20 accessions that have moderate stripe rust APR with infection type (IT<5), and about 20 additional accessions that have novel seedling resistance (IT<3). We have genotyped the collection using genotyping by sequencing (GBS) and the 90K SNP chip array. GBS yielded a total 341K SNP that were filtered to 150K informative SNP. The 90K assay resulted in 11K informative SNP. We have conducted a genome-wide association scan (GWAS) and found one significant locus on 6BL ( -log p >5). Two novel loci were found for seedling resistance. Further investigation of the 6BL locus and the effect of Yr36 showed that the 6BL locus and the Yr36 have additive effect and that the presence of favorable alleles of both loci results in reduction of 2 grades in the IT score. To identify alleles conferring adaption to extreme climatic conditions, we have associated the patterns of genomic variation in wild emmer with historic climate data from the accessions’ collection sites. The analysis of population stratification revealed four genetically distinct groups of wild emmer accessions coinciding with their geographic distribution. Partitioning of genomic variance showed that geographic location and climate together explain 43% of SNPs among emmer accessions with 19% of SNPs affected by climatic factors. The top three bioclimatic factors driving SNP distribution were temperature seasonality, precipitation seasonality, and isothermality. Association mapping approaches revealed 57 SNPs associated with these bio-climatic variables. Out of 21 unique genomic regions controlling heading date variation, 10 (~50%) overlapped with SNPs showing significant association with at least one of the three bioclimatic variables. This result suggests that a substantial part of the genomic variation associated with local adaptation in wild emmer is driven by selection acting on loci regulating flowering. Conclusions: Wild emmer can serve as a good source for novel APR and seedling R genes for stripe rust resistance. APR for stripe rust is a complex trait conferred by several loci that may have an additive effect. GWAS is feasible in the wild emmer population, however, its detection power is limited. A panel of wild emmer tagged with more than 150K SNP is available for further GWAS of important traits. The insights gained by the bioclimatic-gentic associations should be taken into consideration when planning conservation strategies.