نتائج البحث - "Genetics, Genomics, and Proteomics"

1

Plan upravljanja istraživačkim podacima projekta Imunomodulacijski učinci mastocita i eozinofila u mikrookolišu tumora mokraćnog mjehura

المؤلفون: Korać Prlić, Jelena

مصطلحات موضوعية: HRZZ, eozinofili, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Genetics, Genomics and Proteomics, tumor mokraćnog mjehura, MEFST, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Genetika, genomika i proteomika čovjeka, mastociti

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=od______4112::d81db03083087f6c48b1d10b6aab3768Test
https://repozitorij.svkst.unist.hr/islandora/object/mefst:2044Test

2

Identification of novel monogenic causes of segmental progeroid syndromes

المؤلفون: Lessel, Davor

المساهمون: Marinović Terzić, Ivana, Polašek, Ozren, Korać Prlić, Jelena, Čikeš Čulić, Vedrana

مصطلحات موضوعية: Medicina, prerano starenje, Medical sciences, analiza sekvenci DNK, studije genetske povezanosti, Progeria, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Genetics, Genomics and Proteomics, Premature Aging, progerija, udc:61(043.3), DNA Sequence Analysis, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Genetika, genomika i proteomika čovjeka, Genetic Association Studies

الوصف: Segmentni progeroidni sindromi iznimno su rijetki, klinički i genetski heterogeni poremećaji karakterizirani znakovima preuranjenog/ubrzanog starenja koji zahvaćaju više tkiva ili organa. Cilj ovdje predstavljenih studija bio je identificirati nove monogene uzroke odabranih segmentnih progeroidnih sindroma. Koristeći kombinaciju različitih genetskih analiza, primarno koristeći tehnologije sekvenciranja sljedeće generacije, popraćene u određenim slučajevima dubinskom funkcionalnom karakterizacijom, koristeći i stanične i životinjske modele, identificirao sam bialelne mutacije u SPRTN, MDM2 i POLR3A, kao genetske uzroke Ruijs-Aalfsovog sindroma (OMIM # 616200), Lessel-Kubischovog sindroma (OMIM # 618681) i Wiedemann-Rautenstrauchovog sindroma (OMIM # 264090). Utjecaj ovih rezultata je dvostruk. Prvo, kao i u slučaju identifikacije novog genetskog uzroka za bilo koji monogenski poremećaj, ovi rezultati omogućuju postavljanje ispravne dijagnoze, procjenu prognoze, točnu procjenu rizika sličnih poremećaja u članovima obitelji bolesnika, te u sve većem broju slučajevi omogućuju individualiziranu podršku i preventivni program. Drugo, iz translacijske perspektive, posebno mutacije u SPRTN i MDM2, nude snažnu osnovu za daljnja istraživanja s ciljem daljnjeg razjašnjavanja patofiziološke osnove karcinogeneze i stoga identificiranja novih i/ili poboljšanih strategija ciljanja u terapiji raka.
Segmental progeroid syndromes are extremely rare, clinically and genetically heterogeneous disorders characterized by signs of premature / accelerated aging affecting multiple tissues or organs. The aim of the here presented studies was to identify novel monogenic causes of selected segmental progeroid syndromes. Using a combination of different genetic analyses, primarily utilizing next-generation sequencing technologies, accompanied in certain cases by in-depth functional characterization, using both cellular and animal models, I have identified biallelic mutations in SPRTN, MDM2 and POLR3A, as genetic causes of Ruijs-Aalfs syndrome (OMIM # 616200), Lessel-Kubisch syndrome (OMIM # 618681) and Wiedemann–Rautenstrauch syndrome (OMIM # 264090), respectively. The impact of these results is two-fold. First, as in case of identification of novel genetic cause for any monogenic disorder, these results enable establishment of the proper diagnosis, assessment of the prognosis, accurate estimation of the risk of similar disorders in the patient’s family members, and in the growing number of cases enable individualized support and prevention program. Secondly, from the translational perspective, especially mutations in SPRTN and MDM2, offer a strong basis for further studies aiming to further elucidate the pathophysiologic basis of carcinogenesis and hence identify novel and/or improved targeting strategies in cancer therapy.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::32d657c14ebc5e801fa6379549aabeeaTest
https://urn.nsk.hr/urn:nbn:hr:171:120702Test

3

A novel likely pathogenic variant in the RUNX1 gene as the cause of congenital thrombocytopenia

المؤلفون: Despotović, Marta, Pereza, Nina, Peterlin, Borut, Ostojić, Saša, Golob, B, Maver, A, Roganović, Jelena

المصدر: Balkan Journal of Medical Genetics
Volume 25
Issue 1

مصطلحات موضوعية: BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Genetics, Genomics and Proteomics, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Genetics, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Genetika, genomika i proteomika čovjeka, Blood Platelet Disorders, Genetic Testing, Thrombocytopenia, Genetics (clinical)

الوصف: Introduction Heterozygous pathogenic and likely pathogenic sequence variants in the RUNX1 (Runt-related Transcription Factor 1) gene are a common genetic cause of decreased platelet count and/or platelet dysfunction and an increased risk of developing myelodysplasia and acute myeloid leukemia. The majority of causative variants are substitutions, which rarely occur de novo. The aim of this case report is to present a patient with congenital thrombocytopenia caused by a deletion variant in exon 9 in the RUNX1 gene. Case report A one-month-old male infant was admitted to the Clinical Hospital Center Rijeka because of anemia and thrombocytopenia verified in the course of an acute viral infection. During follow-up, he occasionally had petechiae and ecchymoses on the lower extremities after mild trauma, with no other symptoms. The patient had persistent slightly decreased values of platelets with normal morphology, but with pathological aggregation with adrenaline and adenosine diphosphate. Due to the unclear etiology of persistent mild thrombocytopenia, he was referred for genetic testing at the age of five. Genomic DNA was isolated from the patient’s peripheral blood and whole-exome sequencing was performed using the next-generation sequencing method. A heterozygous frameshift variant, c.1160delG (NM_001754.4), was identified in exon 9. The variant is classified as likely pathogenic. Conclusion To the best of our knowledge, the heterozygous variant c.1160delG in the RUNX1 gene was first described in our patient. Although pathogenic variants in the RUNX1 genes are very rare, persistently low platelet counts of unclear etiology should raise suspicion of an underlying genetic disorder.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee8d2181717637f8bd6e11d0454a64a2Test
https://urn.nsk.hr/urn:nbn:hr:184:600519Test

4

Non-genetic physicians’ knowledge, attitudes and behavior towards medical genetics

المؤلفون: Tea Mladenić, Martina Mavrinac, Sanja Dević Pavlić, Anna Malnar, Matea Matić, Sara Mikić, Saša Ostojić, Nina Pereza

المصدر: Wiener Klinische Wochenschrift
Volume 1

مصطلحات موضوعية: Medical education, Human genetics, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Genetics, Genomics and Proteomics, Human behaviour, Genetics research, General Medicine, Genetic literacy, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Genetika, genomika i proteomika čovjeka

الوصف: To examine the knowledge, behavior, and attitudes toward medical genetics among obstetrics and gynecology, pediatrics, and neurology residents and specialists, who encounter the highest number of patients with specific genetic disorders, in their everyday practice. The cross-sectional study involved 182 nongenetic residents and specialists in the Republic of Croatia, who completed a validated online questionnaire anonymously and voluntarily. The questionnaire consisted of five groups of questions: general information, knowledge, behavior in practice, attitude toward genetic testing, and additional education in medical genetics. The median score for overall knowledge of medical genetics was 70.2% among obstetrician-gynecologists, 80.5% among pediatricians, and 76.7% among neurologists (P < 0.001, lowest median in obstetrician- gynecologists). When asked about their behavior in daily practice, around 90% of respondents admitted the possibility of not recognizing patients with genetic disorders, which is why more than 90% emphasized the need for additional education in medical genetics. In addition, the respondents showed a positive attitude toward genetic testing, but they did not feel educated enough to interpret the results of genetic testing. The results highlight the need for further genetic education of non-genetic health professionals, which would lead to greater confidence and ability to recognize patients with genetic disorders, select the appropriate genetic testing method and achieve more efficient communication with patients.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6d68112265da0ac44a6dfe8f53bbaddTest
https://doi.org/10.1007/s00508-023-02152-0Test

5

Osvrt na primjenu neinvazivnog prenatalnog testiranja slobodno cirkulirajuće DNK fetusa iz krvi majke

المؤلفون: Tadić, Ana, Barišić, Anita, Vraneković, Jadranka

المصدر: Liječnički vjesnik
Volume 145
Issue 1-2

مصطلحات موضوعية: BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Genetics, Genomics and Proteomics, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Genetika, genomika i proteomika čovjeka

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::94adc2b13f03d662c2e187034c1c9806Test
https://repository.medri.uniri.hr/islandora/object/medri:7414/datastream/FILE0Test

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DNMT3B rs2424913 as a Risk Factor for Congenital Heart Defects in Down Syndrome

المؤلفون: Dijana Majstorović, Anita Barišić, Ivana Babić Božović, Iva Bilić Čače, Neven Čače, Mauro Štifanić, Jadranka Vraneković

المصدر: Genes
Volume 14
Issue 3
Pages: 576

مصطلحات موضوعية: MTRR, Down syndrome, DNA methyltransferase, single-nucleotide polymorphism, congenital heart defect, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Genetics, Genomics and Proteomics, MTHFR, Genetics, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Genetika, genomika i proteomika čovjeka, Genetics (clinical)

الوصف: Impairments of the genes that encode enzymes that are involved in one-carbon metabolism because of the presence of gene polymorphisms can affect the methylation pattern. The altered methylation profiles of the genes involved in cardiogenesis may result in congenital heart defects (CHDs). The aim of this study was to investigate the association between the MTHFR rs1801133, MTHFR rs1801131, MTRR rs1801394, DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms and congenital heart defects in Down syndrome (DS) individuals. The study was conducted on 350 participants, including 134 DS individuals with CHDs (DSCHD+), 124 DS individuals without CHDs (DSCHD−), and 92 individuals with non-syndromic CHD. The genotyping was performed using the PCR–RFLP method. A statistically significant higher frequency of the DNMT3B rs2424913 TT in the DSCHD+ individuals was observed. The DNMT3B rs2424913 TT genotype, as well as the T allele, had significantly higher frequencies in the individuals with DS and atrial septal defects (ASDs) in comparison with the individuals with DS and other CHDs. Furthermore, our results indicate a statistically significant effect of the DNMT3B rs1569686 TT genotype in individuals with non-syndromic CHDs. The results of the study suggest that the DNMT3B rs2424913 TT genotypes may be a possible predisposing factor for CHDs in DS individuals, and especially those with ASDs.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8706e8bdbb74ee276fbb31ea13e0a279Test
https://doi.org/10.3390/genes14030576Test

7

Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels

المؤلفون: Nikolina Pleić, Tatijana Zemunik, Ivana Gunjača, Mirjana Babić Leko

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 44, p 44 (2022)
International Journal of Molecular Sciences
Volume 23
Issue 1

الوصف: Calciotropic hormones, parathyroid hormone (PTH) and calcitonin are involved in the regulation of bone mineral metabolism and maintenance of calcium and phosphate homeostasis in the body. Therefore, an understanding of environmental and genetic factors influencing PTH and calcitonin levels is crucial. Genetic factors are estimated to account for 60% of variations in PTH levels, while the genetic background of interindividual calcitonin variations has not yet been studied. In this review, we analyzed the literature discussing the influence of environmental factors (lifestyle factors and pollutants) on PTH and calcitonin levels. Among lifestyle factors, smoking, body mass index (BMI), diet, alcohol, and exercise were analyzed; among pollutants, heavy metals and chemicals were analyzed. Lifestyle factors that showed the clearest association with PTH levels were smoking, BMI, exercise, and micronutrients taken from the diet (vitamin D and calcium). Smoking, vitamin D, and calcium intake led to a decrease in PTH levels, while higher BMI and exercise led to an increase in PTH levels. In terms of pollutants, exposure to cadmium led to a decrease in PTH levels, while exposure to lead increased PTH levels. Several studies have investigated the effect of chemicals on PTH levels in humans. Compared to PTH studies, a smaller number of studies analyzed the influence of environmental factors on calcitonin levels, which gives great variability in results. Only a few studies have analyzed the influence of pollutants on calcitonin levels in humans. The lifestyle factor with the clearest relationship with calcitonin was smoking (smokers had increased calcitonin levels). Given the importance of PTH and calcitonin in maintaining calcium and phosphate homeostasis and bone mineral metabolism, additional studies on the influence of environmental factors that could affect PTH and calcitonin levels are crucial.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fee3139c3f41c24515024954a070d34aTest
https://www.mdpi.com/1422-0067/23/1/44Test

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A multicenter study of genetic testing for Parkinson’s disease in the clinical setting

المؤلفون: Anja Kovanda, Valentino Rački, Gaber Bergant, Dejan Georgiev, Dušan Flisar, Eliša Papić, Marija Brankovic, Milena Jankovic, Marina Svetel, Nataša Teran, Aleš Maver, Vladimir S. Kostic, Ivana Novakovic, Zvezdan Pirtošek, Martin Rakuša, Vladimira Vuletić, Borut Peterlin

المصدر: npj Parkinson's Disease
Volume 8
Issue 1

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Parkinson's disease, Genetic testing, Neurology, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Genetics, Genomics and Proteomics, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Neurology, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Neurologija, Neurology (clinical), BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Genetika, genomika i proteomika čovjeka

الوصف: Parkinson’s disease (PD) guidelines lack clear criteria for genetic evaluation. We assessed the yield and rationale of genetic testing for PD in a routine clinical setting on a multicenter cohort of 149 early-onset and familial patients by exome sequencing and semi-quantitative multiplex ligation-dependent probe amplification of evidence-based PD-associated gene panel. We show that genetic testing for PD should be considered for both early-onset and familial patients alike, and a clinical yield of about 10% in the Caucasian population can be expected.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9480bc35340c5460c74d898a922f68a0Test
https://repository.medri.uniri.hr/islandora/object/medri:7061/datastream/FILE0Test

9

SNHG17 , as an EMT‐related lncRNA, promotes the expression of c‐Myc by binding to c‐Jun in esophageal squamous cell carcinoma

المؤلفون: Xiaoliang Liang, Yanli Guo, Zhiming Dong, Bo Feng, Gaoyan Wang, Supeng Shen, Jia Liang, Wei Guo

المصدر: Cancer Science

مصطلحات موضوعية: Genetics, Genomics and Proteomics, Male, Cancer Research, Epithelial-Mesenchymal Transition, Esophageal Neoplasms, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-myc, Mice, Downregulation and upregulation, Cell Movement, Transcription (biology), Cell Line, Tumor, metastasis, Animals, Humans, PI3K/AKT/mTOR pathway, Cell Proliferation, Neoplasm Staging, Chemistry, c-jun, EMT, RNA, Promoter, Original Articles, General Medicine, Long non-coding RNA, esophageal squamous cell carcinoma, SNHG17, Up-Regulation, Gene Expression Regulation, Neoplastic, Oncology, c‐Myc, Cancer research, Original Article, Female, RNA, Long Noncoding, Chromatin immunoprecipitation, Neoplasm Transplantation

الوصف: Dysregulation of long noncoding RNA SNHG17 is associated with the occurrence of several tumors; however, its role in esophageal squamous cell carcinoma (ESCC) remains obscure. The present study demonstrated that SNHG17 was upregulated in ESCC tissues and cell lines, induced by TGF‐β1, and associated with poor survival. It is also involved in the epithelial‐to‐mesenchymal transition (EMT) process. The mechanism underlying SNHG17‐regulated c‐Myc was detected by RNA immunoprecipitation, RNA pull‐down, chromatin immunoprecipitation, and luciferase reporter assays. SNHG17 was found to directly regulate c‐Myc transcription by binding to c‐Jun protein and recruiting the complex to specific sequences of the c‐Myc promoter region, thereby increasing its expression. Moreover, SNHG17 hyperactivation induced by TGF‐β1 results in PI3K/AKT pathway activation, promoting cells EMT, forming a positive feedback loop. Furthermore, SNHG17 facilitated ESCC tumor growth in vivo. Overall, this study demonstrated that the SNHG17/c‐Jun/c‐Myc axis aggravates ESCC progression and EMT induction by TGF‐β1 and may serve as a new therapeutic target for ESCC.
SNHG17 was upregulated and associated with poor survival in ESCC. TGF‐β1 induced SNHG17 involved in the epithelial‐to‐mesenchymal transition process and activated the PI3K/AKT pathway. Mechanistically, SNHG17 was found to directly regulate c‐Myc transcription by binding to c‐Jun protein and recruiting the complex to specific sequences of the c‐Myc promoter region. SNHG17 aggravated ESCC growth in vivo.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a7d8e3bd349447cd0001be2afe30024cTest
https://doi.org/10.1111/cas.15184Test

10

Predictive value of EGFR mutation in non–small‐cell lung cancer patients treated with platinum doublet postoperative chemotherapy

المصدر: Cancer Science

مصطلحات موضوعية: Genetics, Genomics and Proteomics, Male, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.drug_class, medicine.medical_treatment, next‐generation sequencing, non‐squamous non–small‐cell lung cancer, Pemetrexed, Vinorelbine, medicine.disease_cause, postoperative chemotherapy, Tyrosine-kinase inhibitor, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Precision Medicine, Lung cancer, Cisplatin, Chemotherapy, business.industry, High-Throughput Nucleotide Sequencing, Original Articles, Sequence Analysis, DNA, General Medicine, Prognosis, medicine.disease, Survival Analysis, ErbB Receptors, Treatment Outcome, Chemotherapy, Adjuvant, Mutation, Biomarker (medicine), Original Article, Female, KRAS, EGFR mutation, business, medicine.drug

الوصف: The mutation status of tumor tissue DNA (n = 389) of resected stage II‐III non‐squamous non–small‐cell lung cancer (Ns‐NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG‐TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation‐positive status had a significantly shorter recurrence‐free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22‐2.21; P = .0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30‐2.44; P = .0003 for disease stage; and HR, 1.57; 95% CI, 1.15‐2.16; P = .0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II‐III Ns‐NSCLC patients. This result supports a role for mandatory molecular diagnosis of early‐stage Ns‐NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum‐based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).
Mutation status of stage II‐III Ns‐NSCLC (n = 389) was analyzed using targeted deep sequencing. Patients with an EGFR mutation‐positive status had a significantly shorter recurrence‐free survival (RFS). Both the pathological stage and EGFR mutation status were independent prognostic factors for RFS.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03ca09f58c4088f4c7865801d9b76203Test
https://doi.org/10.1111/cas.15171Test

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