Letteratura scientifica selezionata sul tema "Rare genetic disease"
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Articoli di riviste sul tema "Rare genetic disease"
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Rahit, K. M. Tahsin Hassan, e Maja Tarailo-Graovac. "Genetic Modifiers and Rare Mendelian Disease". Genes 11, n. 3 (25 febbraio 2020): 239. http://dx.doi.org/10.3390/genes11030239.
Testo completoAbstract (sommario):
Despite advances in high-throughput sequencing that have revolutionized the discovery of gene defects in rare Mendelian diseases, there are still gaps in translating individual genome variation to observed phenotypic outcomes. While we continue to improve genomics approaches to identify primary disease-causing variants, it is evident that no genetic variant acts alone. In other words, some other variants in the genome (genetic modifiers) may alleviate (suppress) or exacerbate (enhance) the severity of the disease, resulting in the variability of phenotypic outcomes. Thus, to truly understand the disease, we need to consider how the disease-causing variants interact with the rest of the genome in an individual. Here, we review the current state-of-the-field in the identification of genetic modifiers in rare Mendelian diseases and discuss the potential for future approaches that could bridge the existing gap.
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Millán, José M., e Gema García-García. "Genetic Testing for Rare Diseases". Diagnostics 12, n. 4 (25 marzo 2022): 809. http://dx.doi.org/10.3390/diagnostics12040809.
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Rasso, A., K. Boukhari, H. Baybay, S. Elloudi, Z. Douhi e FZ Mernissi. "A Rare Genetic Diseases; Incontinentia Pigmenti: A Case Report". Journal of Clinical Research and Reports 3, n. 3 (6 marzo 2020): 01–02. http://dx.doi.org/10.31579/2690-1919/060.
Testo completoAbstract (sommario):
A 3 years-old girl, born of a 25-year-old mother, and of 30-year-old father, with a 1st degree consanguineous marriage. She was born full term after an uneventful pregnancy. History of similar disease was not present in her family. The parents consulted pour management of skin lesion. with no associated functional signs including no mental retardation, no epilepsy. they report that her skin had been fiery red at the birth time and vesicles had developed shortly afterwards. Then the lesions had cleared gradually and left linear hypo-pigmentation. On clinical examination, showed a facial asymmetry, especially mandibular. Hypopigmented atrophic streaks were seen in her face abdomen, back and limbs, with a baschko-linear path. And she had a syndactyly from the toes of the feet. And. The disease was diagnosed as Incontinentia pigmenti (IP). The ophthalmic exam was normal. Her genetic counseling was otherwise normal. A dental radio-panoramic, and MRI of the cerebral, and lumbosacral spine have been requested.
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Walsh, Roddy, Rafik Tadros e Connie R. Bezzina. "When genetic burden reaches threshold". European Heart Journal 41, n. 39 (29 aprile 2020): 3849–55. http://dx.doi.org/10.1093/eurheartj/ehaa269.
Testo completoAbstract (sommario):
Abstract Rare cardiac genetic diseases have generally been considered to be broadly Mendelian in nature, with clinical genetic testing for these conditions predicated on the detection of a primary causative rare pathogenic variant that will enable cascade genetic screening in families. However, substantial variability in penetrance and disease severity among carriers of pathogenic variants, as well as the inability to detect rare Mendelian variants in considerable proportions of patients, indicates that more complex aetiologies are likely to underlie these diseases. Recent findings have suggested genetic variants across a range of population frequencies and effect sizes may combine, along with non-genetic factors, to determine whether the threshold for expression of disease is reached and the severity of the phenotype. The availability of increasingly large genetically characterized cohorts of patients with rare cardiac diseases is enabling the discovery of common genetic variation that may underlie both variable penetrance in Mendelian diseases and the genetic aetiology of apparently non-Mendelian rare cardiac conditions. It is likely that the genetic architecture of rare cardiac diseases will vary considerably between different conditions as well as between patients with similar phenotypes, ranging from near-Mendelian disease to models more akin to common, complex disease. Uncovering the broad range of genetic factors that predispose patients to rare cardiac diseases offers the promise of improved risk prediction and more focused clinical management in patients and their families.
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V Chandrasekhar. "Rare Diseases - Orphan Drugs". TELANGANA JOURNAL OF IMA 02, n. 02 (2022): 25–32. http://dx.doi.org/10.52314/tjima.2022.v2i2.82.
Testo completoAbstract (sommario):
Rare diseases (RDs) are a class of diseases that do not affect most of the population. Apart from the common diseases that affect most people, some severely rare diseases often pose unique challenges to society and the healthcare systems in India. According to the National Institute of Health (NIH), the F.D.A., and the National Organization for Rare Disorders (NORD), a rare disease is any disease, disorder, illness or condition affecting fewer than 200,000 people in the United States as defined by the Orphan Drug Designation Program. However, 95% of rare diseases currently have no treatment available. Healthcare Experts estimate that around 7000 rare diseases have been identified globally, out of which 450 have been reported in India, like hemophilia, thalas-semia, sickle cell anemia, and Pompe’s disease. Rare diseases come in many forms, including cancers and auto-immune diseases. Drugs for rare diseases are among the highest-priced medications on the market than other common drugs. A medical advisory board of nationally recognized and specialized physicians can help build in-depth case management tools and clinical decision support systems to develop and advance novel therapies. Recognition of carriers harbouring clinically pathogenic genetic vari-ations is essential to provide proper genetic counselling to the patient and management. The precise delineation of distinct RDs is possible through a meticulous clinical evaluation of the patients and their genetic screening. The Electronic Health Record (E.H.R.) helps foster collaboration and better outcomes. A holistic approach should be integrated across health care providers, both at the pharmacy and medical level, that helps improve patient experience and outcomes and reduce costs. Strong health poli-cies and initiatives are required both from private and government institutions for orphan drug development. A separate course on Clinical Genetics must be included in the academic curriculum of medical students in order to provide them knowledge on the basic concepts of genetics and its applications in human health.
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Bellen, Hugo J., Michael F. Wangler e Shinya Yamamoto. "The fruit fly at the interface of diagnosis and pathogenic mechanisms of rare and common human diseases". Human Molecular Genetics 28, R2 (22 giugno 2019): R207—R214. http://dx.doi.org/10.1093/hmg/ddz135.
Testo completoAbstract (sommario):
Abstract Drosophila melanogaster is a unique, powerful genetic model organism for studying a broad range of biological questions. Human studies that probe the genetic causes of rare and undiagnosed diseases using massive-parallel sequencing often require complementary gene function studies to determine if and how rare variants affect gene function. These studies also provide inroads to disease mechanisms and therapeutic targets. In this review we discuss strategies for functional studies of rare human variants in Drosophila. We focus on our experience in establishing a Drosophila core of the Model Organisms Screening Center for the Undiagnosed Diseases Network (UDN) and concurrent fly studies with other large genomic rare disease research efforts such as the Centers for Mendelian Genomics. We outline four major strategies that use the latest technology in fly genetics to understand the impact of human variants on gene function. We also mention general concepts in probing disease mechanisms, therapeutics and using rare disease to understand common diseases. Drosophila is and will continue to be a fundamental genetic model to identify new disease-causing variants, pathogenic mechanisms and drugs that will impact medicine.
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More, Avinash Narayan. "Gaucher’s disease : a rare genetic disorder". International Journal of Scientific and Research Publications 12, n. 10 (24 ottobre 2022): 321–24. http://dx.doi.org/10.29322/ijsrp.12.10.2022.p13044.
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Voelker, Rebecca. "First Drug for Rare Genetic Disease". JAMA 317, n. 5 (7 febbraio 2017): 466. http://dx.doi.org/10.1001/jama.2017.0028.
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Sannikova, A. V., R. M. Fayzullina, Z. A. Shangareeva, I. D. Sartaniya e G. R. Bayazitova. "RARE GENETIC DISEASE: BORING – OPITZ SYNDROME". Научное обозрение. Медицинские науки (Scientific Review. Medical Sciences), n. 1 2025 (2025): 22–28. https://doi.org/10.17513/srms.1430.
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Kutsev, S. I., e S. Moiseev. "Family genetic screening in rare hereditary diseases". Clinical pharmacology and therapy 31, n. 4 (13 novembre 2021): 6–12. http://dx.doi.org/10.32756/0869-5490-2021-4-6-12.
Testo completoAbstract (sommario):
Family genetic testing of probands with newly diagnosed rare hereditary diseases including Fabry disease improves early diagnosis and allows to initiate specific treatment, if available, at earlier stage in affected family members. Diagnosis of Fabry disease, an X-linked lysosomal storage disorder affecting kidneys, heart, brain and other organs, is usually late due to low awareness of physicians about rare diseases. Moreover, early symptoms can be non-specific (e.g. gastrointestinal disorders and autonomic neuropathy) or misleading (e.g. recurrent unexplained fever) whereas characteristic skin rash and keratopathy (cornea verticillata) are frequently overlooked. Undiagnosed patients with Fabry disease can be detected by screening in at-risk populations, such as patients with end-stage renal disease undergoing dialysis or renal transplantation, patients with unexplained left ventricular hypertrophy, and young adults with a history of stroke or transient ischemic attack who have a higher prevalence of the disease compared to general population. High-risk screening paves the way to family screening to identify affected relatives, including children, who can benefit from earlier treatment and genetic counselling. The major barriers to family screening include costs of testing, cultural and societal issues, stigma associated with a diagnosis of genetic disease, low contacts in the family, weak infrastructure, national regulations.
Tesi sul tema "Rare genetic disease"
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Mistry, Vanisha. "Uncovering rare genetic variants predisposing to coeliac disease". Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8649.
Testo completoAbstract (sommario):
Coeliac disease is a common (1% prevalence) inflammatory disease of the small intestine, involving the role of tissue transglutaminase and HLA-‐DQ binding immuno-‐dominant wheat peptides. The disease is highly heritable, however, at most only 40% of this heritability is explained by HLA-‐DQ and risk variants from genome wide association and fine mapping studies. The hypothesis of the research in this thesis is that rare (minor allele frequency <0.5%) mutations of large effect size (odds ratios ~2 – 5) exist, especially in multiply affected pedigrees, which account for the missing heritability of disease. NimbleGen exome capture and Illumina GAIIx high throughput sequencing was performed in 75 coeliac disease individuals from 55 multiply affected families. Candidate genes were chosen from various analytical strategies: linkage, shared variants between multiple related subjects and gene burden tests for multiple potentially causal variants. Highly multiplexed amplicon sequencing, using Fluidigm technology, of all RefSeq exons from 24 candidate genes in 2,304 coeliac cases and 2,304 controls was performed to locate further rare variation. Gene burden tests on a highly stringent post quality control dataset identified no significant associations (P<1x10-‐3) at the resequenced candidate genes. The strategy of sequencing multiply affected families, and deep follow up of candidate genes, has not identified new disease risk mutations. Common variants (and other factors, e.g. environmental) may instead account for familial clustering in this common autoimmune disease.
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Zhao, Jing. "Rare and common genetic variant associations with quantitative human phenotypes". Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/53923.
Testo completoAbstract (sommario):
This dissertation aims at investigating the association between genotypes and phenotypes in human. Both common and rare regulatory variants have been studied. The phenotypes include disease risk, clinical traits and gene expression levels. This dissertation describes three different types of association study. The first study investigated the relationship between common variants and three sub-clinical traits as well as three complex diseases in the Center for Health Discovery and Well Being study (CHDWB). The second study is GWAS analysis of TNF-α and BMI/CRP conducted as a contribution to meta-GWAS analyses of these traits with investigators at the University of Groningen in the Netherlands, and the 1000 Genomes Consortium. The third study was the most original contribution of my thesis as it assessed the association between rare regulatory variants in promoter regions and gene expression levels. The results clearly show an enrichment of rare variants at both extremes of gene expression. This dissertation provides insight into how common and rare variants associate with broadly-defined quantitative phenotypes. The demonstration that rare regulatory variants make a substantial contribution to gene expression variation has important implications for personalized medicine as it implies that de novo and other rare alleles need to be considered as candidate effectors of rare disease risk.
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Tang, Wai-kiu, e 鄧慧翹. "Re-sequencing of neuregulin 1 to search for rare variants in Chinese hirschsprung patients". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46599897.
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Brems, Matthew William. "The Rare Disease Assumption: The Good, The Bad, and The Ugly". The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429881892.
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Bick, Alexander George. "At the Heart of the Genome: Rare Genetic Variation, Cardiovascular Disease, and Therapy". Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11399.
Testo completoAbstract (sommario):
Studies of large families with inherited single gene disorders identified a role of rare genetic variation as a cause of disease and enabled gene-based diagnosis. The increasing availability of population-scale genomic sequencing implies the potential to extend gene-based diagnosis from individuals with monogenic disease to the prediction of disease risk in the general population. Cardiovascular disease (CVD), as a highly heritable condition with significant public health burden, represents an excellent place to consider the promise and limitations of extending our understanding of rare variation in single gene disorders to the general population.
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Lim, Teng Ting. "Exploring the genetic landscape of complex diseases using the recessive model". Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11490.
Testo completoAbstract (sommario):
High-throughput sequencing technologies have changed the way we identify, study and understand the role of rare variation in Mendelian diseases. Sequencing in complex diseases have proven to be more challenging to interpret, but methods and approaches are being developed to aid in our understanding of variation in these diseases.
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Jackson, Victoria Emily. "Investigation into the role of rare genetic variation in lung function and chronic obstructive pulmonary disease". Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38645.
Testo completoAbstract (sommario):
Lung Function is a physiological measurement used for monitoring respiratory health and in the diagnosis of chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Lung function and COPD are influenced by a combination of environmental and genetic factors. This thesis aims to investigate the genetic basis of these traits, with a particular focus on the effect of low frequency and rare genetic variants, so far largely overlooked in genome-wide association studies (GWAS). An analysis of exome array data and COPD identifies novel associations between COPD risk and low frequency single nucleotide polymorphisms (SNPs) in MOCS3 and IFIT3 and between a rare SNP in SERPINA12 and percent predicted forced expiratory volume in one second (FEV1) in COPD cases. Recently developed methods for the meta-analysis of gene-based tests are empirically evaluated and shown to be approximately equivalent to a mega-analysis using individual level data for a quantitative trait. These methods are then applied in a meta-analysis of exome array data and quantitative lung function measures. This meta-analysis identifies no gene-based associations; however genome-wide significant (P < 5x10⁻⁸) single variant associations are identified in two novel regions: a SNP near LY86 associated with the ratio of FEV1 to forced vital capacity (FVC) and a SNP near FGF10 associated with FVC in ever smokers. Finally the largest GWAS to date of two lung function flow measures (peak expiratory flow [PEF] and forced expiratory flow between 25% and 75% of FVC [FEF25-75]) is described. The overlap in variants associated with PEF and FEF25-75 and volumetric measures of lung function (FEV1, FVC and FEV1/FVC) is examined, and 10 SNPs are identified as showing association with PEF (P < 5x10⁻⁸), but no other lung function trait with P < 5x10⁻⁵. These findings have the potential to provide insight into the biological mechanisms underlying lung health and disease.
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Schubert, Jeffrey A. B. S. "The Use of Genetic Analyses and Functional Assays for the Interpretation of Rare Variants in Pediatric Heart Disease". University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535724045195581.
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Katsumata, Yuriko. "STATISTICAL ANALYSES TO DETECT AND REFINE GENETIC ASSOCIATIONS WITH NEURODEGENERATIVE DISEASES". UKnowledge, 2017. https://uknowledge.uky.edu/epb_etds/17.
Testo completoAbstract (sommario):
Dementia is a clinical state caused by neurodegeneration and characterized by a loss of function in cognitive domains and behavior. Alzheimer’s disease (AD) is the most common form of dementia. Although the amyloid β (Aβ) protein and hyperphosphorylated tau aggregates in the brain are considered to be the key pathological hallmarks of AD, the exact cause of AD is yet to be identified. In addition, clinical diagnoses of AD can be error prone. Many previous studies have compared the clinical diagnosis of AD against the gold standard of autopsy confirmation and shown substantial AD misdiagnosis Hippocampal sclerosis of aging (HS-Aging) is one type of dementia that is often clinically misdiagnosed as AD. AD and HS-Aging are controlled by different genetic architectures. Familial AD, which often occurs early in life, is linked to mainly mutations in three genes: APP, PSEN1, and PSEN2. Late-onset AD (LOAD) is strongly associated with the ε4 allele of apolipoprotein E (APOE) gene. In addition to the APOE gene, genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) in or close to some genes associated with LOAD. On the other hand, GRN, TMEM106B, ABCC9, and KCNMB2 have been reported to harbor risk alleles associated with HS-Aging pathology. Although GWAS have succeeded in revealing numerous susceptibility variants for dementias, it is an ongoing challenge to identify functional loci and to understand how they contribute to dementia pathogenesis.
Until recently, rare variants were not investigated comprehensively. GWAS rely on genotype imputation which is not reliable for rare variants. Therefore, imputed rare variants are typically removed from GWAS analysis. Recent advances in sequencing technologies enable accurate genotyping of rare variants, thus potentially improving our understanding the role of rare variants on disease. There are significant computational and statistical challenges for these sequencing studies. Traditional single variant-based association tests are underpowered to detect rare variant associations. Instead, more powerful and computationally efficient approaches for aggregating the effects of rare variants have become a standard approach for association testing. The sequence-kernel association test (SKAT) is one of the most powerful rare variant analysis methods. A recently-proposed scan-statistic-based test is another approach to detect the location of rare variant clusters influencing disease.
In the first study, we examined the gene-based associations of the four putative risk genes, GRN, TMEM106B, ABCC9, and KCNMB2 with HS-aging pathology. We analyzed haplotype associations of a targeted ABCC9 region with HS-Aging pathology and with ABCC9 gene expression. In the second study, we elucidated the role of the non-coding SNPs identified in the International Genomics of Alzheimer’s Project (IGAP) consortium GWAS within a systems genetics framework to understand the flow of biological information underlying AD. In the last study, we identified genetic regions which contain rare variants associated with AD using a scan-statistic-based approach.
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Foster, Robert Graham. "Development of a modular in vivo reporter system for CRISPR-mediated genome editing and its therapeutic applications for rare genetic respiratory diseases". Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/33040.
Testo completoAbstract (sommario):
Rare diseases, when considered as a whole, affect up to 7% of the population, which would represent 3.5 million individuals in the United Kingdom alone. However, while 'personalised medicine' is now yielding remarkable results using recent sequencing technologies in terms of diagnosing genetic conditions, we have made much less headway in translating this patient information into therapies and effective treatments. Even with recent calls for greater research into personalised treatments for those affected by a rare disease, progress in this area is still severely lacking, in part due to the astronomical cost and time involved in bringing treatments to the clinic. Gene correction using the recently-described genome editing technology CRISPR/Cas9, which allows precise editing of DNA, offers an exciting new avenue of treatment, if not cure, for rare diseases; up to 80% of which have a genetic component. This system allows the researcher to target any locus in the genome for cleavage with a short guide-RNA, as long as it precedes a highly ubiquitous NGG sequence motif. If a repair sequence is then also provided, such as a wild-type copy of the mutated gene, it can be incorporated by homology-directed repair (HDR), leading to gene correction. As both guide-RNA and repair template are easily generated, whilst the machinery for editing and delivery remain the same, this system could usher in the era of 'personalised medicine' and offer hope to those with rare genetic diseases. However, currently it is difficult to test the efficacy of CRISPR/Cas9 for gene correction, especially in vivo. Therefore, in my PhD I have developed a novel fluorescent reporter system which provides a rapid, visual read-out of both non-homologous end joining (NHEJ) and homology-directed repair (HDR) driven by CRISPR/Cas9. This system is built upon a cassette which is stably and heterozygously integrated into a ubiquitously expressed locus in the mouse genome. This cassette contains a strong hybrid promoter driving expression of membrane-tagged tdTomato, followed by a strong stop sequence, and then membrane-tagged EGFP. Unedited, this system drives strong expression of membrane-tdTomato in all cell types in the embryo and adult mouse. However, following the addition of CRISPR/Cas9 components, and upon cleavage, the tdTomato is rapidly excised, resulting via NHEJ either in cells without fluorescence (due to imperfect deletions) or with membrane-EGFP. If a repair template containing nuclear tagged-EGFP is also supplied, the editing machinery may then use the precise HDR pathway, which results in a rapid transition from membrane-tdTomato to nuclear- EGFP. Thereby this system allows the kinetics of editing to be visualised in real time and allows simple scoring of the proportion of cells which have been edited by NHEJ or corrected by HDR. It therefore provides a simple, fast and scalable manner to optimise reagents and protocols for gene correction by CRISPR/Cas9, especially compared to sequencing approaches, and will prove broadly useful to many researchers in the field. Further to this, I have shown that methods which lead to gene correction in our reporter system are also able to partially repair mutations found in the disease-causing gene, Zmynd10; which is implicated in the respiratory disorder primary ciliary dyskinesia (PCD), for which there is no effective treatment. PCD is an autosomal-recessive rare disorder affecting motile cilia (MIM:244400), which results in impaired mucociliary clearance leading to neonatal respiratory distress and recurrent airway infections, often progressing to lung failure. Clinically, PCD is a chronic airway disease, similar to CF, with progressive deterioration of lung function and lower airway bacterial colonization. However, unlike CF which is monogenic, over 40 genes are known to cause PCD. The high genetic heterogeneity of this rare disease makes it well suited to such a genome editing strategy, which can be tailored for the correction of any mutated locus.
Libri sul tema "Rare genetic disease"
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G, Thoene Jess, a cura di. Small molecule therapy for genetic disease. Cambridge: Cambridge University Press, 2010.
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Dimond, Rebecca, e Jamie Lewis. Analysing Semi-Structured Interviews: Understanding Family Experience of Rare Disease and Genetic Risk. 1 Oliver's Yard, 55 City Road, London EC1Y 1SP United Kingdom: SAGE Publications, Ltd., 2015. http://dx.doi.org/10.4135/9781473947467.
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Hodge, Russ. Human genetics: Race, population, and disease. New York, NY: Facts on File, 2010.
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Martín, Javier, e Francisco David Carmona, a cura di. Genetics of Rare Autoimmune Diseases. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-03934-9.
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Chin, Nguk Foo. Rare journeys of love. Petaling Jaya, Selangor: Malaysian Rare Disorders Society, 2011.
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Bowman, James E. Genetic variation and disorders in peoples of African origin. Baltimore: Johns Hopkins University Press, 1990.
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National Cancer Institute (U.S.). Clinical Genetics Branch. Inherited bone marrow failure syndromes: Studying families with rare blood disorders and risk of cancer. Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, 2002.
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Congress, on Rare Diseases (2000 Rome Italy). Il Congress on Rare Diseases: Genetic disorders related to dysfunction of cellular organelles : Istituto superiore di sanità : Roma, November 20-22, 2000 : abstract book. Roma: Istituto superiore di sanità, 2000.
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Cushing's Disease: An Often Misdiagnosed and Not So Rare Disorder. Elsevier Science & Technology Books, 2016.
Cerca il testo completoCapitoli di libri sul tema "Rare genetic disease"
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Kanakarajan, Sivakumari, Rajesh Selvaraj e Patheri Kuniyil Kaleena. "Disease Models for Rare Genetic Disorders". In Rare Genetic Disorders, 77–157. Singapore: Springer Nature Singapore, 2024. http://dx.doi.org/10.1007/978-981-99-9323-9_4.
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Biswas, Goutam, Nithar Ranjan Madhu, Bhanumati Sarkar, Soumosish Paul, Hadi Erfani e Qamre Alam. "Rare Genetic Disorders: Unraveling the Pathophysiology, Gene Mutations, and Therapeutic Advances in Fabry Disease and Marfan Syndrome". In Rare Genetic Disorders, 199–219. Singapore: Springer Nature Singapore, 2024. http://dx.doi.org/10.1007/978-981-99-9323-9_7.
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Meroni, Germana. "TRIM E3 Ubiquitin Ligases in Rare Genetic Disorders". In Proteostasis and Disease, 311–25. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-38266-7_14.
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Masood, Afshan, Abeer Malkawi, Anas M. Abdel Rahman e Mohamed Siaj. "Metabolomics of Rare Endocrine, Genetic Disease: A Focus on the Pituitary Gland". In Clinical Metabolomics Applications in Genetic Diseases, 173–87. Singapore: Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-99-5162-8_8.
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Masood, Afshan, Abeer Malkawi, Mohamed Siaj e Anas M. Abdel Rahman. "Metabolomics and Genetics of Rare Endocrine Disease: Adrenal, Parathyroid Glands, and Cystic Fibrosis". In Clinical Metabolomics Applications in Genetic Diseases, 189–206. Singapore: Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-99-5162-8_9.
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Muddyman, Dawn. "The UK10K Project: 10,000 UK Genome Sequences—Accessing the Role of Rare Genetic Variants in Health and Disease". In Assessing Rare Variation in Complex Traits, 87–105. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2824-8_7.
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Cahill, Megan E., e Ruth R. Montgomery. "Analytical Approaches to Uncover Genetic Associations for Rare Outcomes: Lessons from West Nile Neuroinvasive Disease". In Methods in Molecular Biology, 193–203. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2760-0_17.
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Hassan, Muhammad Jawad, Muhammad Faheem e Sabba Mehmood. "Emerging OMICS and Genetic Disease". In Omics Technologies for Clinical Diagnosis and Gene Therapy: Medical Applications in Human Genetics, 93–113. BENTHAM SCIENCE PUBLISHERS, 2022. http://dx.doi.org/10.2174/9789815079517122010010.
Testo completoAbstract (sommario):
Multiomics also described as integrative omics is an analytical approach that combines data from multiple ‘omics’ approaches including genomics, transcriptomics, proteomics, metabolomics, epigenomics, metagenomics and Meta transcriptomics to answer the complex biological processes involved in rare genetic disorders. This omics approach is particularly helpful since it identifies biomarkers of disease progression and treatment progress by collective characterization and quantification of pools of biological molecules within and among the various types of cells to better understand and categorize the Mendelian and non- Mendelian forms of rare diseases. As compared to studies of a single omics type, multi-omics offers the opportunity to understand the flow of information that underlies the disease. A range of omics software and databases, for example WikiPathways, MixOmics, MONGKIE, GalaxyP, GalaxyM, CrossPlatform Commander, and iCluster are used for multi-omics data exploration and integration in rare disease analysis. Recent advances in the field of genetics and translational research have opened new treatment avenues for patients. The innovation in the next generation sequencing and RNA sequencing has improved the ability from diagnostics to detection of molecular alterations like gene mutations in specific disease types. In this chapter, we provide an overview of such omics technologies and focus on methods for their integration across multiple omics layers. The scrupulous understanding of rare genetic disorders and their treatment at the molecular level led to the concept of a personalized approach, which is one of the most significant advancements in modern research which enable researchers to better comprehend the flow of knowledge which underpins genetic diseases.
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"Tay-Sachs Disease: Public Education". In Tay-Sachs Disease. Exon Publications, 2024. http://dx.doi.org/10.36255/tay-sachs-disease-public-education.
Testo completoAbstract (sommario):
Tay-Sachs disease is a rare and serious genetic disorder that affects the nervous system, leading to progressive and often devastating health consequences. This guide explores Tay-Sachs disease in detail, from its origins and genetic basis to its symptoms, diagnosis, treatment options, and life expectancy. Designed for patients, families, and caregivers, this comprehensive resource explains the condition in clear and simple language, providing the information needed to understand and navigate the challenges posed by Tay-Sachs disease. By shedding light on the role of genetics, the importance of early diagnosis, and the current management strategies, this guide serves as a vital resource for those affected by or concerned about this condition.
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"Fabry Disease: Public Education". In Fabry Disease, 1–8. Exon Publications, 2024. http://dx.doi.org/10.36255/fabry-disease-public-education.
Testo completoAbstract (sommario):
Fabry Disease is a rare genetic disorder that disrupts the body’s ability to break down specific fatty substances, leading to their buildup in cells and causing damage to various organs, including the heart, kidneys, and nervous system. This comprehensive guide explores Fabry Disease in detail, addressing its causes, symptoms, types, and genetic inheritance. It provides insights into the diagnostic process, available treatments, and management strategies. By presenting information in clear, simple language, this article aims to educate and support patients, families, and caregivers in understanding and managing this condition effectively.
Atti di convegni sul tema "Rare genetic disease"
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Mladenović, Tamara. "FUNDAMENTAL LEGAL ASPECTS OF THE PRENATAL GENETIC DIAGNOSIS". In International scientific conference challenges and open issues of service law. Vol. 1. University of Kragujevac, Faculty of law, 2024. http://dx.doi.org/10.46793/xxmajsko1.395m.
Testo completoAbstract (sommario):
he field of genetic services within the legal system of the Republic of Serbia was initially regulated in 2015 with the enactment of the Law on Prevention and Diagnosis of Genetic Diseases, Genetically Conditioned Anomalies, and Rare Diseases. This law, commonly known as “Zoja’s Law”, was prompted by the advocacy of parents whose daughter suffered from a rare disease and was denied access to healthcare due to the inability to obtain a diagnosis in Serbia. As a result, the law was introduced to the public with significant attention and is recognized as one of the most modern legal frameworks in Europe concerning the establishment of rights, duties, and responsibilities for participants in medical procedures related to the prevention and diagnosis of genetics diseases, genetically conditioned anomalies, and rare diseases.This law covers several broader areas in the context of genetic testing aimed at establishing a diagnosis, including predictive, prenatal, and postnatal diagnostics. This paper focuses on the analysis of prenatal diagnosis - the genetic testing of embryos or fetuses. In addition to examining the provisions of domestic legislation, special attention will be given to analyzing the European Court of Human Rights (ECtHR) practice regarding member states’ provision of access to these services for individuals. This analysis entails assessing the compatibility of Serbia’s legal framework with European human rights standards, particularly concerning the right to health and reproductive rights. Key issues explored include access to information, consent, privacy, and the balancing of individual rights with societal interests.
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Gomes, Victor Hugo de Souza Silva, Klesia Adaynny Rodrigues, Isadora Soares Constantini de Andrade, Beatriz Fulador, Bianca Barbosa Araldi, Bruno Ludvig Vieira Schaeffler e Heloise Helena Siqueira. "Use of free genetic screening methods in neurology outpatients in cuiaba: advantages and interpretation difficulties". In XIV Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2023. http://dx.doi.org/10.5327/1516-3180.141s1.368.
Testo completoAbstract (sommario):
Introduction: Medical genetics is increasingly gaining in modern medicine, through panels that enable the screening and diagnosis of rare diseases, becoming an effective ally in determination of some pathologies. In 2021, Invitae provided of medical outpatient clinics with kits for collecting genetic material in order to assist the specialist in diagnosing unusual and difficult-to-recognize conditions. In Cuiabá, the residency in Neurology was chosen to host the use of these methods. Objectives and methods: List the genetic tests collected through oral swabs and quantify the diagnoses made, in addition to the difficulty in determining them due to the technical language used. Results: In 12 months, 61 samples were collected, however, only 50 were analyzed. 11 tests were excluded. The analysis identified 30 male, representing 60% of panels, the average age of total sample was 33.64 years (SD). Received results from 20 samples with negative results in search for pathogenic alleles, while 22 showed only uncertain variants, not being conclusive for any diagnosis, just implying reproductive risk. Total of exams analyzed, 8 samples (16%) were positive for pathogenic variants, confirming the diagnosis of rare diseases and enabling appropriate therapeutic measures, initiation of supportive therapies and familiar guidance. Through this method, two patients were diagnosed with Spinal Muscular Atrophy type III, 1 with Wilson’s disease and two others with Niemann-Pick disease type C. Conclusion: Project ended in mid-2022, with the completion of free access to diagnoses. We emphasize that in many cases, access to genetic panel was extremely relevant, helped in the diagnostic direction, making it possible to start therapies for some patients with potentially treatable diseases. However, we encountered some difficulties, mainly in the interpretation of results provided by laboratory, due to extremely technical language and the large amount of information grouped in text. Conclud that medical genetics is extremely important in assisting medicals in diagnosis of rare diseases. However, there is a need for greater access to geneticists as well as genetic tests available in Brazilian Unified Health System.
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Ilcheva, Madlena. "THE EFFECT OF A SPECIALIZED PHYSIOTHERAPY PROGRAM IN AN INFANT WITH A RARE GENETIC DISEASE". In INTERNATIONAL SCIENTIFIC CONGRESS “APPLIED SPORTS SCIENCES”. Scientific Publishing House NSA Press, 2022. http://dx.doi.org/10.37393/icass2022/163.
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ABSTRACT Introduction: The specialized physiotherapy program is a set of purposeful techniques and methodologies, profiled for work with children. Early physical therapy intervention is essential for the prevention and reduction of the pathological impact on the neuromotor capabilities of children with neurological impairment caused by a genetic disease. Purpose: The aim of the study is to monitor the effectiveness of a specialized physiotherapy program in a child with a deviation in neuromotor development. The therapy was performed 5 times a week for 3 months. The object of the study is the influence of physiotherapy in case of deviation in the neuromotor development of an infant with a rare genetic disease. The contingent of the study is 1 infant with a rare genetic disease - isovaleric acidemia and is the only case of a patient with such a disease in Bulgaria. The infant is 9 months old (7 adjusted months). The deviations are expressed in pathologically amplified and persistent primitive reflexes and delay in motor development. We assessed gross motor development by the method of Gross Motor Function Measure – 88 in the beginning and then made a reassessment on the 3rd month from the beginning of the therapy. Results: The analysis of the results shows that the specialized physiotherapy program influenced the neuromotor development of the patient - helping to integrate primitive reflexes; to develop and improve motor skills. Conclusions: Specialized physiotherapy is an effective treatment for neuromotor deviation in infant with a rare genetic disease.
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Nakano, Bruno Eiji, Gabriel Flamarin Cavasana, Paula Carolina Grande Nakazato, Alana Strucker Barbosa, Isabela Badan Fernandes, Eduardo Silveira Marques Branco, Sarah de Souza Chinelato et al. "Huntington Disease-Like 2: a case report". In XIV Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2023. http://dx.doi.org/10.5327/1516-3180.141s1.494.
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Case presentation: Male, 56-year-old, previously epileptic started with involuntary movements in the right hand at 47 years old evolving to torso, incoordination, behavioral and cognition disturbs. Paternal grandmother, father and cousin with similar symptoms, in addition to four asymptomatic children. From the onset of symptoms, it progressively worsened presenting involuntary movements, hallucinations, aggressiveness and neck drop. During the neurological examination had frequent cervical falls, tremors at rest in the limbs, and mood swings. Cranial magnetic resonance imaging (MRI) was with atrophy of the caudate nucleus and putamen. Genetic test for Huntington’s Disease without evidence of characteristic expansion of the disease and Huntington Like 2 Test (Junctophilin-3) compatible with characteristic expansion of the disease. Discussion: Huntington’s Disease Like-2 has an autosomal dominant character. A rare disease related to repetitive mutations of cytosine-thymineguanine in the Junctophilin-3 gene. Frequently among 29–41-year-olds and represented by progressive movement disorders, dementia and psychiatric alterations and survival rate of 10 to 20 years after the onset of symptoms. Atrophy of the caudate and cerebral cortex is identified in cranial MRI. Diagnosis’ based on genetic testing and treatment is symptomatic in addition to genetic counseling. Conclusion: In this case the patient presented progressive movement disorders in addition to psychiatric and cognitive alterations as other family members without previous diagnosis of Huntington disease-like 2. Due to the rarity of the disease beside the genetic chance of hereditary cases follow-up with a specialist for symptomatic family members had been requested in addition to genetic counseling since 50% of siblings are at risk of developing the disease.
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Elias, Stefany, e Maria Luiza Benevides. "Verheij syndrome: a rare cause of intellectual disability". In XIV Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2023. http://dx.doi.org/10.5327/1516-3180.141s1.560.
Testo completoAbstract (sommario):
Case presentation: A 4-year-old boy was born to non-consanguineous parents at 38 weeks. Neonatal anthropometric measurements were normal. Since birth, he presented with global developmental delay, and muscular hypotonia. At present, he shows adequate psychosocial interaction. He has a healthy 3-year-old sister. On physical examination, there are dysmorphisms, such as prominent and pointed ears, long eyelashes, elongated face, flat occipital region, supernumerary teeth, and maxillary hypoplasia. His anthropometric measurements are normal for his age (p50). On neurological examination, he presents with apraxia of speech, axial and appendicular hypotonia, and reduced deep tendon reflexes. Brain magnetic resonance imaging showed a slight thinning of the corpus callosum and mild ectasia of the lateral ventricles. Transthoracic echocardiography and ultrasound of the kidneys and urinary tract were normal. On genetic investigation, no abnormalities were found in karyotype and CGH-Array. Whole exome sequencing showed a pathogenic variant in the PUF60 gene (c.24+1G>C) in heterozygosis. Thus, the patient was diagnosed with Verheij syndrome. The patient is accompanied by physiotherapy, speech therapy, occupational therapy, and a psychopedagogy group. Discussion: Verheij syndrome is a rare condition caused by variants in the PUF60 gene, which encodes a component of the spliceosome. This syndrome is characterized by intellectual disability, delayed growth and neuropsychomotor development, facial dysmorphic features, and osteoarticular abnormalities. Also, there may be heart and kidney disorders. The spectrum of this disease’s manifestations and severity still need to be further explored in future studies, as well as the treatment and prognosis of this condition. Multidisciplinary support is essential for managing the consequences of the disease. This case report reinforces the leveraged importance that genetics has had in the diagnosis of intellectual disabilities.
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WANG, Shih-Shuan, Ionela-Roxana PUIU, Eugen Silviu VRĂJITORU e Marian Stafie. "MILITARY BLOCKCHAIN IN HEALTHCARE TO SUPPORT CLINICAL DATA". In SCIENTIFIC RESEARCH AND EDUCATION IN THE AIR FORCE. Publishing House of "Henri Coanda" Air Force Academy, 2022. http://dx.doi.org/10.19062/2247-3173.2022.23.17.
Testo completoAbstract (sommario):
Using the advent of quick and effective next-generation sequencing technologies, unlinked and dispersed patient data have surfaced as a major problem in diagnosing uncommon diseases. The molecular associated with the rare disease entails comparing a patient’s genetic variant information with the variations more with comparable diseases in a big population. Therefore, discussing information among genetic databases plus laboratories is important in order to identify overlapping outcomes and for identifying the pathogenic importance of variants in order to allow the analysis of rare hereditary diseases. Considered perhaps the most continuous test to be defeated is the patient information will frequently be kept in focal confined admittance vaults as a result of protection and security concerns. An individual arising illustration of such an innovation is military blockchain novelty. As decentralized and conveyed innovation, military blockchain innovation has many engaging properties, for example, information condition and responsibility, that could be utilized to expand the condition, discoverability, and access of patient information, along these lines moving toward a new confided in framework to direct the promotion of patient information sharing.
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Kim, W., D. Qiao, E. K. Silverman, M. H. Cho e NHLBI Trans-Omics in Precision Medicine (TOPMed). "Assessing the Contribution of Rare Genetic Variants to Phenotypes of Chronic Obstructive Pulmonary Disease Using Whole-Genome Sequence Data". In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7150.
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Muhovic, D., B. Smolovic, A. Hodzic e B. Peterlin. "CAROLI'S DISEASE (CD) CAUSED BY VERY RARE GENETIC MUTATION, MISDIAGNOSED WITH ERCP AND MRCP AS PRIMARY SCLEROSING CHOLANGITIS (PSC)". In ESGE Days 2019. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1681852.
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Danhaive, Olivier, Donatella Peca, Renata Boldrini, Sara Tomassetti, Angelo Carloni, Venerino Poletti e Renato Cutrera. "Surfactant Protein C (SP-C) Rare And Common Genetic Variants In Children And Adults With Unexplained Diffuse Lung Disease". In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a5166.
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Starič, Jože, Geč Veren, Rok Marzel e Jožica Ježek. "Sporadic leukosis in cattle". In Zbornik radova 26. medunarodni kongres Mediteranske federacije za zdravlje i produkciju preživara - FeMeSPRum. Poljoprivredni fakultet Novi Sad, 2024. http://dx.doi.org/10.5937/femesprumns24035s.
Testo completoAbstract (sommario):
Sporadic bovine leukosis (SBL) is a rare neoplastic disease in cattle. It represents a unique challenge for veterinary medicine due to its sporadic occurrence, peculiar clinical presentation and unclear etiology. SBL manifests in four forms: juvenile lymphosarcoma, adult multicentric leukosis, thymic lymphosarcoma and cutaneous lymphosarcoma. In contrast to enzootic bovine leukosis, which is caused by the bovine leukemia virus (BLV), there is no viral link in sporadic cases. They are thought to be caused by multifactorial interactions between genetic predisposition and environmental factors (e.g. carcinogens or other triggers). The diseases are not contagious. The aim of this paper is to review the current knowledge of SBL, focusing on the clinical presentation, diagnostic challenges and potential risk factors. Although sporadic leukosis accounts for a smaller proportion of leukosis cases in cattle compared to BLV-induced leukosis, the impact on affected individuals is severe. SBL must be differentiated from BLV-induced leukosis (absence of BLV antibodies in the blood and absence of BLV in the tissue), which is a reportable disease in the European Union. SBL usually affects younger cattle, but adult animals can also be affected. Adult multicentric leukosis clinically resembles enzootic bovine leukosis with multicentric lymphoproliferative foci and lymphadenopathy, but the affected animals are negative for BLV antibodies. The diseases are progressive and lead to the death of the animals. Diagnostic confirmation of SBL often requires a combination of histopathologic examination, immunohistochemistry and molecular analyses to differentiate it from other neoplastic diseases in cattle. Risk factors such as exposure to certain environmental toxins or genetic susceptibility are thought to play a role in the development of sporadic leukosis. Further research efforts are needed to elucidate the mechanisms underlying the development of SBL and to develop effective prevention and control strategies to control this sporadic but usually lethal disease in cattle population.
Rapporti di organizzazioni sul tema "Rare genetic disease"
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Wongpiyabovorn, Jongkonnee, Nattiya Hirankarn, Yingyos Avihingsanon, Tewin Tencomnao, Yong Poovorawan e Kriangsak Ruchusatsawat. The association between immunogenetics and genetic susceptibility of psoriasis in Thai population. Chulalongkorn University, 2006. https://doi.org/10.58837/chula.res.2006.27.
Testo completoAbstract (sommario):
Psoriasis is T-cell-mediated skin autoimmunity, required environmental triggers and genetic susceptibility factors to become manifested. Psoriasis is a chronic skin disease characterized by the abnormal hyperproliferation and differentiation of the epidermis, elongated and prominent blood vessels and a thick perivascular lymphocytic infiltrate. Vascular endothelial growth factor (VEGF) gene play important role in pathogenesis of various diseases with angiogenic basis such as breast cancer and autoimmune disease including psoriasis. Many studies analyzed the association of VEGF gene polymorphism in many positions in Caucasian and non-Caucasian. Most reports in some position that really point to important about single nucleotide polymorphism (SNP) with several autoimmune diseases including psoriasis. Although the precise causes of this auto-immune disease remain elusive. It appears to be influenced by stress. The serotonergic system known to depend primarily on the serotonin transporter (5-HTT) may have a role in psoriasis. The serotonin transporter-linked promoter region (5-HTTLPR) polymorphism occurred by insertion/deletion is evident to result in three different length alleles namely S, L as predominant variant alleles and XL as a rare one. These three alleles have 14, 16 and 18 or 20 repetitive DNA sequences, respectively and have been shown to associate with certain neuropsychiatric diseases. Although roles of serotonin and serotonin receptors in psoriasis were investigated, the impact of 5-HTTLPR on psoriasis has not been studied. Therefore, the 5-HTTLPR polymorphism was analyzed to assess whether these variants are associated with psoriasis. Furthermore, having recognized the relationship between oxidative stress and psoriasis, the association between G82S polymorphism in the gene encoding the receptor for advanced glycation end products (RAGE) and psoriasis was investigated. The aims of study, we determine the distribution of VEGF, RAGE and 5-HTTLPR polymorphism in Thai psoriasis patients. We analyzed SNPs within the VEGF (-1557) (C/A), -460(C/T) and +405(C/G)). G82S RAGE and 5-HTTLPR (S, L and XL) gene polymorphism. In population-based case-control study, allele and genotype frequencies of each marker were compared between 234 unrelated healthy volunteers and 154 chronic plapue psoriasis patients (102 early-onset and 52 late-onset psoriasis) for VEGF gene, one hundred seventy eight healthy donors and 134 psoriasis patients for RAGE gene and one hundred twenty seven healthy controls and 142 psoriasis patients for 5-HTTLPR gene. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-sequence specific primer (PCR-SSP) methods. The results, The -460 TT or CT compared to CC VEGF genotype were found to be significantly risk associated with early-onset psoriasis patients compared with healthy controls (p=0.0450, odds ratio (OR) =4.67, 95% confidence interval (CI) = 1.03-29.52). Interesthingly, haplotype analysis revealed that the CTG haplotype was found to be significantly associated with susceptibility to psoriasis and early-onset psoriasis compared with healthy controls (p=0.0460, OR=1.37, 95% CI=1.00-1.87, p=0.0163, OR=1.54, 95% CI=1.08-2.18, respectively). Moreover, VEGF plasma concentration was not significantly different between groups of haplotype in psoriasis patients. A significantly greater 82A G82S RAGE allele frequency was observed in psoriatic patients than in control subjects (p=0.001 OR=0.52 95% CI=0.35-0.78). Finally, the 5HTTPR polymorphism was no significant change in the allelic frequencies between psoriatic and control subjects (p=0.531, OR=1.15, 95% CI=0.78-1.70). Thus, the result demonstrated that the CTG haplotype and -460 C/T VEGF polymorphism may be used as a genetic marker for early-onset psoriasis in Thais but the 5-HTTLPR was not associated with psoriasis in Thai population. Furthermore, the G82S RAGE polymorphism was associated with psoriasis, and further investigations should be carried out to gain insights into its molecular mechanism in psoriasis.
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Dubief, Jessie. Setting Standards of Care Quality! EURORDIS - Rare Diseases Europe, febbraio 2020. http://dx.doi.org/10.70790/igio1525.
Testo completoAbstract (sommario):
This report presents the results of the H-CARE Pilot Survey for the four European Reference Networks (ERNs) that initated this study conducted by Rare Barometer: ERN GENTURIS, ERKNet, ERN Lung and eUROGEN. The goal of this study was to test the feasibility of measuring rare disease patients’ and carers’ experience with the care delivered by healthcare providers who are part of an ERN. A Topic Expert Committee composed of patient representatives, clinicians and managers from ERNs GENTURIS, ERKNet, Lung and eUROGEN selected a patient reported Experience Measure (PREM) questionnaire validated for chronic conditions, the Patient Assessment of Care for Chronic Conditions Short Form (PACIC-S). This questionnaire was administered by Rare Barometer, with the participation of hospital units that were members of the four ERNs of the pilot. This report presents the results of the pilot study for the 1,319 patients and carers who assessed European healthcare providers treating rare diseases affecting kidneys, lungs, the urogenital area and genetic tumour risk syndromes: Patients had a better healthcare experience when they were treated by hospital units that are part of a ERN. The PACIC-S showed good internal consistency and good construct validity in German, French, English and Spanish. But content validity was low as all aspects of care experience for rare diseases were not covered by the scale, showing that the PACIC-S did not fully capture the healthcare experience of people living with a rare disease. Recommendations for the development and validation of a new scale for RDs include planning onsite distribution of paper questionnaires in specialised hospital units, in addition to online distribution towards patient organisations and on social media, in order to reach a sufficient number of respondents for each ERN and language.
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Joel, Daniel M., Steven J. Knapp e Yaakov Tadmor. Genomic Approaches for Understanding Virulence and Resistance in the Sunflower-Orobanche Host-Parasite Interaction. United States Department of Agriculture, agosto 2011. http://dx.doi.org/10.32747/2011.7592655.bard.
Testo completoAbstract (sommario):
Oroginal Objectives: (i) identify DNA markers linked to the avirulence (Avr) locus and locate the Avr locus through genetic mapping with an inter-race Orobanche cumana population; (ii) develop high-throughput fingerprint DNA markers for genotypingO. cumana races; (iii) identify nucleotide binding domain leucine rich repeat (NB-LRR) genes encoding R proteins conferring resistance to O. cumana in sunflower; (iv) increase the resolution of the chromosomal segment harboring Or₅ and related R genes through genetic and physical mapping in previously and newly developed mapping populations of sunflower; and (v) develop high-throughput DNA markers for rapidly and efficiently identifying and transferring sunflower R genes through marker-assisted selection. Revisions made during the course of project: Following changes in O. cumana race distribution in Israel, the newly arrived virulent race H was chosen for further analysis. HA412-HO, which was primarily chosen as a susceptible sunflower cultivar, was more resistant to the new parasite populations than var. Shemesh, thus we shifted sunflower research into analyzing the resistance of HA412-HO. We exceeded the deliverables for Objectives #3-5 by securing funding for complete physical and high-density genetic mapping of the sunflower genome, in addition to producing a complete draft sequence of the sunflower genome. We discovered limited diversity between the parents of the O. cumana population developed for the mapping study. Hence, the developed DNA marker resources were insufficient to support genetic map construction. This objective was beyond the scale and scope of the funding. This objective is challenging enough to be the entire focus of follow up studies. Background to the topic: O. cumana, an obligate parasitic weed, is one of the most economically important and damaging diseases of sunflower, causes significant yield losses in susceptible genotypes, and threatens production in Israel and many other countries. Breeding for resistance has been crucial for protecting sunflower from O. cumana, and problematic because new races of the pathogen continually emerge, necessitating discovery and deployment of new R genes. The process is challenging because of the uncertainty in identifying races in a genetically diverse parasite. Major conclusions, solutions, achievements: We developed a small collection of SSR markers for genetic mapping in O. cumana and completed a diversity study to lay the ground for objective #1. Because DNA sequencing and SNPgenotyping technology dramatically advanced during the course of the study, we recommend shifting future work to SNP discovery and mapping using array-based approaches, instead of SSR markers. We completed a pilot study using a 96-SNP array, but it was not large enough to support genetic mapping in O.cumana. The development of further SNPs was beyond the scope of the grant. However, the collection of SSR markers was ideal for genetic diversity analysis, which indicated that O. cumanapopulations in Israel considerably differ frompopulations in other Mediterranean countries. We supplied physical and genetic mapping resources for identifying R-genes in sunflower responsible for resistance to O. cumana. Several thousand mapped SNP markers and a complete draft of the sunflower genome sequence are powerful tools for identifying additional candidate genes and understanding the genomic architecture of O. cumana-resistanceanddisease-resistance genes. Implications: The OrobancheSSR markers have utility in sunflower breeding and genetics programs, as well as a tool for understanding the heterogeneity of races in the field and for geographically mapping of pathotypes.The segregating populations of both Orobanche and sunflower hybrids are now available for QTL analyses.
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Amuzu-Aweh, Esinam Nancy, Muhammed Walugembe, Boniface Baboreka Kayang e Amandus Pachificus Muhairwa. Genetic Parameters and Genomic Regions Associated with Growth Rate and Response to Newcastle Disease in Local Chicken Ecotypes in Ghana and Tanzania. Ames (Iowa): Iowa State University, gennaio 2018. http://dx.doi.org/10.31274/ans_air-180814-376.
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Kistler, Harold Corby, Talma Katan e Dani Zamir. Molecular Karyotypes of Pathogeic Strains of Fusarium oxysporum. United States Department of Agriculture, giugno 1995. http://dx.doi.org/10.32747/1995.7604927.bard.
Testo completoAbstract (sommario):
Genetic diversity of pathogenic strains of the fungus Fusarium oxysporum was determied by analysis of electrophoretic karyotype, as well as by DNA variation detected by Restriction Fragment Length Polymorphisms (RFLPs) and Random Amplified Polymorphic DNAs (RAPDs). The electrophoretic karyotypes for 130 isolates of the fungus pathogenic to tomato, melon, and banana were analyzed. Electrophoretic karyotype variation, reflected in differences in apparent chromosome number and genome size, was observed even among isolates from the same host and sub specific category. Sub specific categories studied were forma specialis, vegetative compatibility group (VCG) and race. Chromosome number and genome size variation was less for isolates within the same VCG than for the collection of isolates as a whole. RFLP and RAPD analysis were performed on 62 isolates of F. oxysporum from tomato and melon. Polygenetic trees were constructed from genetic diversity data. The results support the hypothesis that isolates belonging to the same VCG originate from a single ancestor compared to other isolates. The results do not support the hypothesis that all isolates belonging to the same forma specialis originate from a common ancestor. These conclusions have profound implication for breeding resistance to diseases caused by particular formae speciales of F. oxysporum.
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Dechow, Chad Daniel, M. Cohen-Zinder, Morris Soller, Y. Tzfati, A. Shabtay, E. Lipkin, T. Ott e W. Liu. Genotypes and phenotypes of telomere length in Holstein cattle, actors or reporters. Israel: United States-Israel Binational Agricultural Research and Development Fund, 2020. http://dx.doi.org/10.32747/2020.8134156.bard.
Testo completoAbstract (sommario):
Selection programs aiming at improving health and survival in cattle are complicated by low heritability estimates, the fact that true herd life and carcass quality is not known until the end of an animal's life, and that many health conditions manifest late in life. Young animals are now heavily favored in breeding programs because low generation intervals accelerate the rate of genetic progress, which means selection decisions must be made before phenotypic observation of health and survival is feasible. Moreover, profitability is compromised when livestock producers raise animals that fail to produce due to health failure or that do not meet quality standards. Telomere length (TL) was hypothesized as a biomarker that could be recorded early in life, be associated with health and survival, and have higher heritability than other measures of health. Thus, our research aims were to: 1, determine associations of TL with health, wellbeing and production in Holsteins raised for dairy or beef purposes; 2, determine TL heritability, genetic variance, and genetic correlations with cow health and performance; and 3, map quantitative trait loci affecting TL and provide TL genomic predictions to industry partners and breeders. There were not significant changes made to the research plan during the project, but the timeline of the project was not met. Laboratory processing of samples was significantly delayed due to Covid along with some sample collection. TL measurements from >1100 animals across the US and Israel are available to date. TL declines modestly with age, in agreement with observations from other species. A genomic analysis was conducted using a single-step approach and TL had a moderate heritability estimate of 20% across age groups. The initial genome-wide association-analysis indicated that TL is a quantitative trait whose expression is influenced by effects across the genome. Moreover, there is a strong association of calf and dam TL at birth. Genetic relationships with health and survival were ascertained through correlations of genomic estimated breeding values (gEBV) for TL with gEBV for other traits routinely recording in national genetic evaluations. Higher TL is genetically associated with longer herd-life, a greater likelihood that cows will avoid premature on-farm death, and reduced disease incidence. The relationship appeared to be strongest when TL was measured during the first two years of life. Based on genotyping different cell types, there was evidence that maternal and colostral derived cells are present in newborns, which could bias TL measurements during the first weeks of life to a small degree. The implications of this research are that TL is a promising trait to include in multiple trait selection programs because it is heritable, available early in life, and correlated with longevity and health. Our TL reference population is currently being expanded, and genomic estimated breeding values will be disseminated to industry partners upon completion of the reference population so that they can evaluate the utility of incorporating TL into their breeding programs.
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Steffenson, B. J., I. Mayrose, Gary J. Muehlbauer e A. Sharon. ing and comparative sequence analysis of powdery mildew and leaf rust resistance gene complements in wild barley. Israel: United States-Israel Binational Agricultural Research and Development Fund, 2021. http://dx.doi.org/10.32747/2021.8134173.bard.
Testo completoAbstract (sommario):
Our overall, long-term goal is to exploit the genetic diversity present in cereal wild relatives for the development of cultivars with durable disease resistance. Our specific objectives for this proposal were to: 1) Utilize Association Genetics Resistance Gene Enrichment Sequencing (AgRenSeq) to identify and clone powdery mildew and leaf rust resistance gene complements in wild barley and 2) Conduct comparative sequence analyses of the cloned resistance genes to elucidate the basis of their specificity and evolution. The deployment of resistant cultivars is the most effective, economically efficient, and environmentally sound means of controlling plant diseases, especially in small grain cereals. The systems selected for study in this proposal are barley (Hordeum vulgare ssp. vulgare, Hvv), its wild progenitor (Hordeum vulgare ssp. spontaneum, Hvs) and the powdery mildew (Blumeria graminis f. sp. hordei, Bgs) and leaf rust (Puccinia hordei, Ph) pathogens. We compiled a diverse panel of Hvs accessions (the Wild Barley Diversity Collection or WBDC; N = 314) from across its native range and evaluated it to 40 isolates of Bgs and 12 isolates of Ph. We obtained genomic DNA sequences enriched for Nucleotide Binding Site-Leucine Rich Repeat (NLR) type resistance genes for 203 WBDC accessions, plus cultivar Morex for which the first reference genome sequence of barley was based. We assembled the 250 bp Illumina sequencing reads into contigs using CLC assembly cell. From this effort, we successfully assembled the sequences of 201 WBDC accessions plus Morex and used NLR Parser to identify contigs containing NLR genes. AgRenSeq was then used to identify k-mers (short oligonucleotide sequences of length k) that were associated with resistance to each isolate of the two pathogens. This analysis was performed individually for all WBDC accessions and each individual pathogen race (9,898 host accession x pathogen race combinations). We visualized the results from these analyses in Manhattan plots and identified 311 and 144 peaks for powdery mildew and leaf rust resistance, respectively. The next step in the analysis was to identify the contigs associated with the peaks in the Manhattan plots. BLAST (Basic Local Alignment Search Tool) searches were employed to identify closely related contigs in other WBDC accessions or in Morex. We identified two candidate R genes that were only present in resistant WBDC accessions. One of these was present in seven WBDC lines and was associated with resistance to four leaf rust isolates. BLAST analysis of this gene revealed that it was Rph15, one of the most widely effective leaf rust resistance genes reported in Hordeum. This gene was cloned and functionally validated in association with our Australian colleagues (Cheng et al., 2021). We are currently in the process of cloning six of other resistance genes: four for powdery mildew and two for leaf rust. As the contigs do not contain much of the promoter sequences, we have employed a genome walking approach to identify 2,500 bp of promoter sequence. To speed up and simplify the cloning of resistance genes from the WBDC, the PI established the International Wild Barley Sequencing Consortium (IWBSC; https://iwbsc.umn.edu/) comprised of over 60 researchers from 14 different countries and raised over $150,000 through crowdfunding to pay for 10X depth sequence coverage. Genome-wide association study (GWAS) of whole genome sequencing (WGS) data identified extremely strong and clear signals of association for several resistance genes which will facilitate gene cloning in concert with a wild barley pan-genome currently under construction. The cloning of multiple resistance gene can facilitate the development of durably resistant cultivars by inserting, through transgenesis, cassettes of multiple resistance genes.
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Tangkijvanith, Pisit. Prevalence and Clinical Significance of Hepatitis B Viral Genotypes and Mutations. Faculty of Medicine, Chulalongkorn University, 2006. https://doi.org/10.58837/chula.res.2006.24.
Testo completoAbstract (sommario):
Hepatitis B virus (HBV) infection is a major public health problem, with more than 400 million HBV carriers estimated worldwide. Chronic HBV infection is associated with a diverse clinical spectrum of liver damage ranging from asymptomatic carrier status, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). There have been increasing lines of evidence to indicate influences of HBV genotypes and mutations on the outcome of liver disease, particularly the development of HCC. The project is aimed to study the prevalence and clinical significance of genotypes and mutations in Precore/core and X regions of HBV in Thai patients. Our study demonstrate that genotype C and B were the predominant strains, accounting for approximately 75 and 20% of patients, respectively. Patients with HBV genotype C, compared to those with genotype B, had a higher positive rate of HBeAg and exhibited earlier progression of cirrhosis and HCC. However, there was no difference in the risk of developing HCC and its prognosis between patients with genotypes B and C. Furthermore, certain X gene mutations and, particularly, CP mutations in young patients may contribute to the development of HCC As the genetic variability of HBV differs geographically and the data available in Thailand are still limited, our study will provide useful information regarding the epidemiology and clinical relevance of HBV genotypes and mutations in Thai populations.
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Tipton, Kelley, Brian F. Leas, Emilia Flores, Christopher Jepson, Jaya Aysola, Jordana Cohen, Michael Harhay et al. Impact of Healthcare Algorithms on Racial and Ethnic Disparities in Health and Healthcare. Agency for Healthcare Research and Quality (AHRQ), dicembre 2023. http://dx.doi.org/10.23970/ahrqepccer268.
Testo completoAbstract (sommario):
Objectives. To examine the evidence on whether and how healthcare algorithms (including algorithm-informed decision tools) exacerbate, perpetuate, or reduce racial and ethnic disparities in access to healthcare, quality of care, and health outcomes, and examine strategies that mitigate racial and ethnic bias in the development and use of algorithms. Data sources. We searched published and grey literature for relevant studies published between January 2011 and February 2023. Based on expert guidance, we determined that earlier articles are unlikely to reflect current algorithms. We also hand-searched reference lists of relevant studies and reviewed suggestions from experts and stakeholders. Review methods. Searches identified 11,500 unique records. Using predefined criteria and dual review, we screened and selected studies to assess one or both Key Questions (KQs): (1) the effect of algorithms on racial and ethnic disparities in health and healthcare outcomes and (2) the effect of strategies or approaches to mitigate racial and ethnic bias in the development, validation, dissemination, and implementation of algorithms. Outcomes of interest included access to healthcare, quality of care, and health outcomes. We assessed studies’ methodologic risk of bias (ROB) using the ROBINS-I tool and piloted an appraisal supplement to assess racial and ethnic equity-related ROB. We completed a narrative synthesis and cataloged study characteristics and outcome data. We also examined four Contextual Questions (CQs) designed to explore the context and capture insights on practical aspects of potential algorithmic bias. CQ 1 examines the problem’s scope within healthcare. CQ 2 describes recently emerging standards and guidance on how racial and ethnic bias can be prevented or mitigated during algorithm development and deployment. CQ 3 explores stakeholder awareness and perspectives about the interaction of algorithms and racial and ethnic disparities in health and healthcare. We addressed these CQs through supplemental literature reviews and conversations with experts and key stakeholders. For CQ 4, we conducted an in-depth analysis of a sample of six algorithms that have not been widely evaluated before in the published literature to better understand how their design and implementation might contribute to disparities. Results. Fifty-eight studies met inclusion criteria, of which three were included for both KQs. One study was a randomized controlled trial, and all others used cohort, pre-post, or modeling approaches. The studies included numerous types of clinical assessments: need for intensive care or high-risk care management; measurement of kidney or lung function; suitability for kidney or lung transplant; risk of cardiovascular disease, stroke, lung cancer, prostate cancer, postpartum depression, or opioid misuse; and warfarin dosing. We found evidence suggesting that algorithms may: (a) reduce disparities (i.e., revised Kidney Allocation System, prostate cancer screening tools); (b) perpetuate or exacerbate disparities (e.g., estimated glomerular filtration rate [eGFR] for kidney function measurement, cardiovascular disease risk assessments); and/or (c) have no effect on racial or ethnic disparities. Algorithms for which mitigation strategies were identified are included in KQ 2. We identified six types of strategies often used to mitigate the potential of algorithms to contribute to disparities: removing an input variable; replacing a variable; adding one or more variables; changing or diversifying the racial and ethnic composition of the patient population used to train or validate a model; creating separate algorithms or thresholds for different populations; and modifying the statistical or analytic techniques used by an algorithm. Most mitigation efforts improved proximal outcomes (e.g., algorithmic calibration) for targeted populations, but it is more challenging to infer or extrapolate effects on longer term outcomes, such as racial and ethnic disparities. The scope of racial and ethnic bias related to algorithms and their application is difficult to quantify, but it clearly extends across the spectrum of medicine. Regulatory, professional, and corporate stakeholders are undertaking numerous efforts to develop standards for algorithms, often emphasizing the need for transparency, accountability, and representativeness. Conclusions. Algorithms have been shown to potentially perpetuate, exacerbate, and sometimes reduce racial and ethnic disparities. Disparities were reduced when race and ethnicity were incorporated into an algorithm to intentionally tackle known racial and ethnic disparities in resource allocation (e.g., kidney transplant allocation) or disparities in care (e.g., prostate cancer screening that historically led to Black men receiving more low-yield biopsies). It is important to note that in such cases the rationale for using race and ethnicity was clearly delineated and did not conflate race and ethnicity with ancestry and/or genetic predisposition. However, when algorithms include race and ethnicity without clear rationale, they may perpetuate the incorrect notion that race is a biologic construct and contribute to disparities. Finally, some algorithms may reduce or perpetuate disparities without containing race and ethnicity as an input. Several modeling studies showed that applying algorithms out of context of original development (e.g., illness severity scores used for crisis standards of care) could perpetuate or exacerbate disparities. On the other hand, algorithms may also reduce disparities by standardizing care and reducing opportunities for implicit bias (e.g., Lung Allocation Score for lung transplantation). Several mitigation strategies have been shown to potentially reduce the contribution of algorithms to racial and ethnic disparities. Results of mitigation efforts are highly context specific, relating to unique combinations of algorithm, clinical condition, population, setting, and outcomes. Important future steps include increasing transparency in algorithm development and implementation, increasing diversity of research and leadership teams, engaging diverse patient and community groups in the development to implementation lifecycle, promoting stakeholder awareness (including patients) of potential algorithmic risk, and investing in further research to assess the real-world effect of algorithms on racial and ethnic disparities before widespread implementation.
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Ficht, Thomas, Gary Splitter, Menachem Banai e Menachem Davidson. Characterization of B. Melinensis REV 1 Attenuated Mutants. United States Department of Agriculture, dicembre 2000. http://dx.doi.org/10.32747/2000.7580667.bard.
Testo completoAbstract (sommario):
Brucella Mutagenesis (TAMU) The working hypothesis for this study was that survival of Brucella vaccines was directly related to their persistence in the host. This premise is based on previously published work detailing the survival of the currently employed vaccine strains S19 and Rev 1. The approach employed signature-tagged mutagenesis to construct mutants interrupted in individual genes, and the mouse model to identify mutants with attenuated virulence/survival. Intracellular survival in macrophages is the key to both reproductive disease in ruminants and reticuloendothelial disease observed in most other species. Therefore, the mouse model permitted selection of mutants of reduced intracellular survival that would limit their ability to cause reproductive disease in ruminants. Several classes of mutants were expected. Colonization/invasion requires gene products that enhance host-agent interaction or increase resistance to antibacterial activity in macrophages. The establishment of chronic infection requires gene products necessary for intracellular bacterial growth. Maintenance of chronic infection requires gene products that sustain a low-level metabolism during periods characterized little or no growth (1, 2). Of these mutants, the latter group was of greatest interest with regard to our originally stated premise. However, the results obtained do not necessarily support a simplistic model of vaccine efficacy, i.e., long-survival of vaccine strains provides better immunity. Our conclusion can only be that optimal vaccines will only be developed with a thorough understanding of host agent interaction, and will be preferable to the use of fortuitous isolates of unknown genetic background. Each mutant could be distinguished from among a group of mutants by PCR amplification of the signature tag (5). This approach permitted infection of mice with pools of different mutants (including the parental wild-type as a control) and identified 40 mutants with apparently defective survival characteristics that were tentatively assigned to three distinct classes or groups. Group I (n=13) contained organisms that exhibited reduced survival at two weeks post-infection. Organisms in this group were recovered at normal levels by eight weeks and were not studied further, since they may persist in the host. Group II (n=11) contained organisms that were reduced by 2 weeks post infection and remained at reduced levels at eight weeks post-infection. Group III (n=16) contained mutants that were normal at two weeks, but recovered at reduced levels at eight weeks. A subset of these mutants (n= 15) was confirmed to be attenuated in mixed infections (1:1) with the parental wild-type. One of these mutants was eliminated from consideration due to a reduced growth rate in vitro that may account for its apparent growth defect in the mouse model. Although the original plan involved construction of the mutant bank in B. melitensis Rev 1 the low transformability of this strain, prevented accumulation of the necessary number of mutants. In addition, the probability that Rev 1 already carries one genetic defect increases the likelihood that a second defect will severely compromise the survival of this organism. Once key genes have been identified, it is relatively easy to prepare the appropriate genetic constructs (knockouts) lacking these genes in B. melitensis Rev 1 or any other genetic background. The construction of "designer" vaccines is expected to improve immune protection resulting from minor sequence variation corresponding to geographically distinct isolates or to design vaccines for use in specific hosts. A.2 Mouse Model of Brucella Infection (UWISC) Interferon regulatory factor-1-deficient (IRF-1-/- mice have diverse immunodeficient phenotypes that are necessary for conferring proper immune protection to intracellular bacterial infection, such as a 90% reduction of CD8+ T cells, functionally impaired NK cells, as well as a deficiency in iNOS and IL-12p40 induction. Interestingly, IRF-1-/- mice infected with diverse Brucella abortus strains reacted differently in a death and survival manner depending on the dose of injection and the level of virulence. Notably, 50% of IRF-1-/- mice intraperitoneally infected with a sublethal dose in C57BL/6 mice, i.e., 5 x 105 CFU of virulent S2308 or the attenuated vaccine S19, died at 10 and 20 days post-infection, respectively. Interestingly, the same dose of RB51, an attenuated new vaccine strain, did not induce the death of IRF-1-/- mice for the 4 weeks of infection. IRF-1-/- mice infected with four more other genetically manipulated S2308 mutants at 5 x 105 CFU also reacted in a death or survival manner depending on the level of virulence. Splenic CFU from C57BL/6 mice infected with 5 x 105 CFU of S2308, S19, or RB51, as well as four different S2308 mutants supports the finding that reduced virulence correlates with survival Of IRF-1-/- mice. Therefore, these results suggest that IRF-1 regulation of multi-gene transcription plays a crucial role in controlling B. abortus infection, and IRF-1 mice could be used as an animal model to determine the degree of B. abortus virulence by examining death or survival. A3 Diagnostic Tests for Detection of B. melitensis Rev 1 (Kimron) In this project we developed an effective PCR tool that can distinguish between Rev1 field isolates and B. melitensis virulent field strains. This has allowed, for the first time, to monitor epidemiological outbreaks of Rev1 infection in vaccinated flocks and to clearly demonstrate horizontal transfer of the strain from vaccinated ewes to unvaccinated ones. Moreover, two human isolates were characterized as Rev1 isolates implying the risk of use of improperly controlled lots of the vaccine in the national campaign. Since atypical B. melitensis biotype 1 strains have been characterized in Israel, the PCR technique has unequivocally demonstrated that strain Rev1 has not diverted into a virulent mutant. In addition, we could demonstrate that very likely a new prototype biotype 1 strain has evolved in the Middle East compared to the classical strain 16M. All the Israeli field strains have been shown to differ from strain 16M in the PstI digestion profile of the omp2a gene sequence suggesting that the local strains were possibly developed as a separate branch of B. melitensis. Should this be confirmed these data suggest that the Rev1 vaccine may not be an optimal vaccine strain for the Israeli flocks as it shares the same omp2 PstI digestion profile as strain 16M.