Relevant bibliographies by topics / Variant rara

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Academic literature on the topic 'Variant rara'

Author: Grafiati
Published: 4 June 2021
Last updated: 13 February 2022

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Journal articles on the topic "Variant rara"

1

Rabade, Nikhil, Goutham Raval, Shruti Chaudhary, PG Subramanian, Rohan Kodgule, Swapnali Joshi, Prashant Tembhare, et al. "MOLECULAR HETEROGENEITY IN ACUTE PROMYELOCYTIC LEUKEMIA - A SINGLE CENTRE EXPERIENCE FROM INDIA." Mediterranean Journal of Hematology and Infectious Diseases 10, no. 1 (January 1, 2018): 2018002. http://dx.doi.org/10.4084/mjhid.2018.002.

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Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over 7 different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require combination of advanced cytogenetic and molecular techniques for accurate characterization. Heterogeneity occurs not only at the molecular level but also at clinico-pathological level influencing treatment response and outcome. In this case series we describe the molecular heterogeneity of APL seen in a single tertiary referral centre with a focus on seven variant APL cases from a single tertiary cancer center in India over a period of two and a half years. We discuss five cases with PLZF-RARA fusion and two novel PML-RARA variants, including a Bcr3 variant involving fusion of PML exon4 and RARA exon3 with an additional 40 nucleotides originating from RARA intron2, another involving exon 6 of PML and exon 3 of RARA with addition of 126 nucleotides, which mapped to the central portion of RARA intron 2 To the best of our knowledge this is the first of kind case series from India
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Adams, Julia, and Mehdi Nassiri. "Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations." Archives of Pathology & Laboratory Medicine 139, no. 10 (October 1, 2015): 1308–13. http://dx.doi.org/10.5858/arpa.2013-0345-rs.

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The majority of patients with acute promyelocytic leukemia (APL) manifest the t(15;17)(q24.1;q21.2) translocation; however, a minor but significant proportion of patients with APL harbor complex, cryptic, or variant translocations, which typically involve RARA. With the exception of ZBTB16/RARA, these variants have similar morphologic and immunophenotypic features as classic APL. Study of the variant forms of APL not only gives insight into the pathogenesis of APL but also allows us to understand the mechanism of retinoid therapy. It is important to identify these cryptic and variant translocations because certain variants, including ZBTB16/RARA and STAT5B/RARA, are resistant to treatment with all-trans retinoic acid, arsenic trioxide, and anthracyclines.
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Bajaj, Preeti, Rajyaguru Devangana, B. S. Shah, and Amrinder Kaur. "Hyperbasophilic Variant of Acute Promyelocytic Leukemia." MVP Journal of Medical Sciences 3, no. 2 (November 17, 2016): 125. http://dx.doi.org/10.18311/mvpjms/2016/v3/i2/7702.

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Acute Promyelocytic Leukemia (APL) is an extremely rare variant of acute myeloid leukemia. APL constitutes around 10-15 % of acute myeloid leukemia in adults. It is commonly diagnosed around 40 years age. Molecular/genetic studies exhibit chromosomal translocation between chromosome 15 and chromosome 17-t(15;17)(q22;q21) and PML-RARa rearrangement. Four variants of APL have been identified: The classic form M<sub>3</sub> hypergranular variant, the microgranular variant, the hyperbasophilic form and zinc-finger form-M<sub>3</sub>r, identified by a different chromosomal translocation, between chromosome 11 and chromosome 17:t(11,17) (q23, q11-12).
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Dowse, Robin T., and Robin M. Ireland. "Variant ZBTB16-RARA translocation: morphological changes predict cytogenetic variants of APL." Blood 129, no. 14 (April 6, 2017): 2038. http://dx.doi.org/10.1182/blood-2016-10-743856.

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Catalano, Alberto, Mark A. Dawson, Karthiga Somana, Stephen Opat, Anthony Schwarer, Lynda J. Campbell, and Harry Iland. "The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia." Blood 110, no. 12 (December 1, 2007): 4073–76. http://dx.doi.org/10.1182/blood-2007-06-095554.

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Abstract We report the molecular and cytogenetic characterization of a novel variant of acute promyelocytic leukemia (APL). The bone marrow showed 88% hypergranular promyelocytes, and the karyotype was 47,XY,+22 [5]/46,XY[30]. Fluorescence in situ hybridization (FISH) indicated disruption and deletion of the 5′-end of the RARA gene. Treatment with all-trans retinoic acid, idarubicin, and arsenic trioxide induced cytogenetic complete remission without morphologic evidence of residual leukemia. The diagnostic marrow was negative for PML-RARA transcripts by reverse transcription–polymerase chain reaction (RT-PCR), but an atypical product was observed. Sequencing showed partial homology to the PRKAR1A gene, encoding the regulatory subunit type I-α of cyclic adenosine monophosphate–dependent protein kinase. RT-PCR using specific primers for PRKAR1A and RARA amplified 2 transcript splice variants of a PRKAR1A-RARA fusion gene, and PRKAR1A and RARA FISH probes confirmed the fusion. This novel PRKAR1A-RARA gene rearrangement is the fifth variant APL in which the RARA partner gene has been identified and the second known rearrangement of PRKAR1A in a malignant disease. This trial was registered at www.actr.org.au with the Australian Clinical Trials Registry as number 12605000070639.
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Zhao, Jie, Liang Jian-Wei, Shuhong Shen, Jing Chen, Hui-Liang Xue, Ben-Shang LI, and Jing-Yan Tang. "The Genetics and Clinical Characteristics of Children Morphologically Diagnosed As Acute Promyelocytic Leukaemia." Blood 132, Supplement 1 (November 29, 2018): 2801. http://dx.doi.org/10.1182/blood-2018-99-112401.

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Abstract Acute promyelocytic leukaemia (APL) is characterized by t(15;17)(q22;q21), resulting in a PML-RARA fusion that is the master driver of APL. A few cases that can't be identified with PML-RARA by using routine methods (karyotype analysis, FISH, and RT-PCR) involve abnormal promyelocytes that are fully in accordance with APL in morphology, cytochemistry, and immunophenotype. To explore the mechanisms involved in pathogenesis and recurrence of morphologically diagnosed APL, we performed comprehensive variant analysis from structural variants (SVs) to single-nucleotide variants (SNVs) in paediatric patients mophologically diagnosed as APL by next generation sequencing. SV analysis using targeted gene sequencing(TGS) in 120 DNA samples from both diagnosis and relapse stage identified 95 samples with RARA rearrangement (including 94 with PML-RARA and one with NPM-RARA) and two samples with KMT2A rearrangement. In the cases failed to be identified with any RARA rearrangement, transcriptome sequencing was applied in the available 13 RNA samples at diagnosis. One case each with CPSF6-RARG, NPM1-CCDC28A, and TBC1D15-RAB21 and two cases with a TBL1XR1-RARB fusion were discovered, which strongly suggested their contributions to leukemogenesis as driver alternations and APL phenotype is inextricably linked to rearrangement of RARA gene. SNV analysis in 75 primary APL samples with RARA rearrangement showed recurrent alternations in FLT3(27%), WT1(13%), USP9X(9%), NRAS(7%), and ARID1A(4%), with a strong potential for involvement in pathogenesis, and WT1as the only gene recurrently mutated in 4/5 samples(3/4 cases) in relapsed APL. WT1 (17.6%), NPM1 (11.8%), NRAS (11.8%), FLT3 (11.8%), and NSD1 (11.8%) were identified as recurrently mutated in 17 primary samples without RARA rearrangement and WT1(44.4%), NPM1 (33.3%), TP53 (33.3%), and RARA (33.3%)as recurrently mutated in 9 relapsed samples. The retrospective study showed the survival rates of APL without RARA rearrangement(8y-EFS=38.7%±17.8%) were much worse than APL with RARA rearrangement(8y-EFS=90.9%±3.9%), which is similar to AML (non-M3) patients(8y-EFS=57.7%±3.0%). Thus,NGS is necessary in cases failed to be identified with RARA rearrangement by karyotype analysis, FISH, and RT-PCR, which can afford accurate diagnosis and treatment guidance. APL phenotype may arise by abnormities of other members of the nuclear receptor superfamily involved in retinoid signaling(RARB or RARG) or even by mechanisms distinct from the formation of aberrant retinoid receptors. Differences in genetic alternations and survival indicated that APL that cannot be identified as having a RARA rearrangement are more reasonably classified as a subclass of AML other than APL, and an AML treatment regimen or individualized treatment should be considered according to the genetic abnormalities. Figue1. (A)Mutational profile between APL with and without RARA rearrangement. (B)Comparison of estimated probability of EFS and OS among APL with and without RARA rearrangement and AML(non-M3) group . “Typical APL” means APL with RARA rearrangement and “Atypical APL” means APL without RARA rearrangement. Disclosures No relevant conflicts of interest to declare.
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Catalano, Alberto, Mark A. Dawson, Karthiga Somana, Stephen S. Opat, Lynda J. Campbell, Anthony P. Schwarer, and Harry J. Iland. "A Novel Fusion of RARA to the PRKAR1A Gene, Encoding the Regulatory Subunit Type-I α of Cyclic AMP Dependent Protein Kinase A, in a Variant Acute Promyelocytic Leukaemia." Blood 108, no. 11 (November 1, 2006): 2343. http://dx.doi.org/10.1182/blood.v108.11.2343.2343.

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Abstract The vast majority of acute promyelocytic leukemia (APL) cases are characterized by the formation of a PML/RARA fusion gene. Disruptions of retinoic acid receptor α (RARα) function have also been described in four types of variant APL in which an alternative partner gene (PLZF, NPM, NUMA, or STAT5B) is fused to RARA. We describe a novel variant APL with a RARA fusion formed by a complex gene rearrangement which is undetectable by conventional cytogenetics. A 66 yr old male with a history of mild thrombocytopenia was diagnosed with APL based on the blood and marrow morphology, the coagulopathy, and a microspeckled PML immunofluorescence pattern. The bone marrow immunophenotype was negative for CD2, CD19, CD34, CD56, CD117 and HLA-DR, and with weak expression of CD13, CD33 and CD11b, a pattern atypical for APL. The diagnostic bone marrow karyotype was 47,XY,+22[5]/46,XY[30] with no t(15;17)(q22;q21). FISH with the Vysis LSI PML/RARA dual fusion translocation probe did not show any fusion signals but there was splitting of an RARA signal on one 17q. A second probe, the Vysis LSI RARA break apart probe, showed deletion of the 5′ RARA probe and the 3′ RARA probe appeared to localize more distally than normal. The Cytocell PML/RARA ES probe also showed no fusion signals but one RARA signal appeared smaller. The diagnostic marrow was negative for PML/RARA transcripts by RT-PCR using PML and RARA specific primers, but an atypical product was observed. Sequencing of this product showed partial homology to the PRKAR1A gene that maps to 17q24 and encodes the regulatory subunit type I-alpha (RIα) of cyclic AMP-dependent protein kinase A. RT-PCR using PRKAR1A and RARA specific primers amplified two transcript splice variants of a PRKAR1A/RARA fusion gene. The shorter out-of-frame fusion transcript lacked PRKAR1A exon 3 and encoded a carboxy-truncated RIα protein. The longer in-frame fusion transcript resulted from cryptic splicing of the first 100 bases of PRKAR1A exon 3 to RARA exon 3, and encoded a chimeric RIα-RARα fusion protein that contained the dimerization domain of RIα and the same carboxy terminal domains of RARα that are found in all other known RARA rearrangements in APL. FISH using a BAC probe (RP11–120M18) encompassing the PRKAR1A gene identified signals on both copies of 17q; a strong signal on the normal 17 and a weaker signal on der(17). Before cytogenetic, FISH and molecular results were available, the patient was registered on the Australasian Leukaemia and Lymphoma Group’s APML4 treatment protocol which includes ATRA, age-adjusted idarubicin and arsenic trioxide. Arsenic was ceased on day 22 due to toxicity. Morphological and cytogenetic FISH complete remission was documented on day 35. A bone marrow biopsy eleven months from original diagnosis showed no evidence of leukemia and PRKAR1A/RARA RT-PCR was indicative of molecular remission. This novel PRKAR1A/RARA gene rearrangement identified in a variant APL is the fifth variant APL in which the RARA partner gene has been identified and the second known rearrangement of PRKAR1A in a malignant disease.
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Redner, Robert L., Lydia C. Contis, Carol Evans, Maureen E. Sherer, and Sofia Shekhter-Levin. "A Novel t(3;17) Variant of Acute Promyelocytic Leukemia with Rearrangement of the RARA Locus." Blood 104, no. 11 (November 16, 2004): 4428. http://dx.doi.org/10.1182/blood.v104.11.4428.4428.

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Abstract The vast majority of patients with Acute Promyelocytic Leukemia (APL, FAB M3) have the t(15;17)(q12;q21) chromosomal translocation. This introduces the gene for PML into the retinoic acid receptor alpha (RARA) locus, which leads to expression of a PML-RARA fusion. There is convincing evidence that expression of PML-RARA underlies the APL phenotype. Yet, there have been identified rare cases of APL that do not manifest t(15;17). Many of these cases exhibit cryptic rearrangements of PML and RARA. However, in a number of cases it has clearly been shown that a fusion protein different than PML-RARA is expressed. These include the t(11;17)(q23;q21) that expresses a PLZF-RARA fusion; t(5;17)(q35;q21) that encodes NPM-RARA; t(11;17)(q13;q21) that encodes NUMA-RARA; and der(17) with duplication of 17q21.3-q23 that fuses STAT5b to RARA. We report here a novel case of APL with t(3;17) with rearrangement of RARA, but not PML. A 72 year old man presented with leukocytosis, anemia, and thrombocytopenia: wbc 20.4 X10E+9/L; hgb 10.3 g/L; PLT 22 x10E+9/L. The wbc differential showed 20% polys, 4% bands, 15% lymphocytes, 19% monocytes, 34% blasts, 1% promyelocyte, 6% myelocyte, 1% metamyelocytes. Auer rods were seen. The bone marrow was hypercellular (approximately 80%), with 88% blasts, 1.7% promyelocytes, 0.3% myelocyte, 0.3% polys, 0.3% eosinophile, 3% monocytes, 0.3% pronormoblasts, 3.7% normoblasts, and 2.3% lymphocytes. The blasts demonstrated prominent cytoplasmic granulation, Flow cytometric analysis showed the blasts to be CD117 positive, myeloperoxidase positive, CD13/33 positive, but lacking CD34 or HLA-DR expression, consistent with a diagnosis of APL. Cytogenetic studies indicated a mosaic abnormal analysis with an apparent normal cell line and one that demonstrated a 47,XY,t(3;17)(p25;q12-21), +8 karyotype. Analysis for PML-RARA expression by RT-PCR was indeterminate, owing to poor quality of the extracted RNA. Fluorescence In Situ Hybridization (FISH) was therefore performed on two hundred unstimulated cells, primarily in interphase, using the Vysis t(15;17) dual color DNA probe. 98.5% of the cells were negative for PML-RARA rearrangement (the value of 1.5% positivity is within the laboratory’s control range for false positives). To confirm that the t(3;17) rearrangement involved the RARA locus, we scored 203 unstimulated cells using the LSI RARA dual color DNA probe. 100% were positive for the RARA gene rearrangement (split signal). Four metaphase cells each showed one fused red/green signal on the normal chromosome 17, one red signal on der (17), and one green signal on the distal arm of chromsome 3. The FISH analysis therefore indicated rearrangement of the RARA, but not the PML locus. The patient expired before treatment could begin. To determine whether the t(3;17) blasts could differentiate (a hallmark of t(15;17) APL), we cultured the bone marrow cells in RPMI 1640 with 10% FCS and 10E-6 M ATRA. At 10 days 58% of the cells resembled metamyelocytes, bands, or mature polys, compared with none in the control culture. This indicates that t(3;17) retains its ability to differentiate in the presence of ATRA, consistent with its classification as a novel variant of APL.
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Yamamoto, Yukiya, Sachiko Tsuzuki, Motohiro Tsuzuki, Kousuke Handa, Yoko Inaguma, and Nobuhiko Emi. "BCOR as a Novel Fusion Partner of Retinoic Acid Receptor Alpha In a t(X;17)(p11;q12) Variant of Acute Promyelocytic Leukemia." Blood 116, no. 21 (November 19, 2010): 1703. http://dx.doi.org/10.1182/blood.v116.21.1703.1703.

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Abstract Abstract 1703 The majority of acute promyelocytic leukemia (APL) cases are characterized by the presence of a PML-RARA fusion gene. In a small subset, RARA is fused to a different partner including PLZF, NPM1, NuMA, STAT5b, PRKAR1A and FIP1L1. Here we identified a novel RARA fusion transcript, BCOR-RARA in a t(X;17)(p11;q12) variant of APL. The patient was a 45-year-old man. Although the patient was clinically responsive to ATRA, repeated standard chemotherapy with ATRA did not effect a cure. The bone marrow promyelocytes had unique morphologic features, including rectangular and round cytoplasmic inclusion bodies. They were more granular than those of AML M2 but less granular than the classical t(15;17) APL. Flow cytometric analysis revealed strong expression of CD13, CD33, CD56, weak expression of CD11c and lack of HLA-DR and CD7. The karyotype analysis detected a novel chromosomal translocation described as 45,-Y, t(X;17)(p11.2;q12)[19]/ 46,XY[1]. FISH analysis indicated one intact and two split signals of RARA and two intact signals of PML. To amplify unknown chimeric fusion transcripts, we performed 5'-RACE. The sequence revealed that BCL6 co-repressor, BCOR cDNA from exons 9 to 12 to be fused to RARA exon 3. By RT-PCR, we confirmed full length chimeric fusion transcripts spanning from the start codon to 4,948 nt of BCOR cDNA (NM_001123384) fused to RARA cDNA from exon 3 to the stop codon. The chimeric cDNA had an in-frame codon from BCOR through RARA, creating a 1,931 amino acid fusion protein. One of the consistent features in all known RARA fusion partners is self-association. To determine whether BCOR-RARA self-associate, we performed co-immunoprecipitation assays. These results showed that BCOR-RARA is able to self-associate both through the region of BCOR-S and the ankyrin repeat domain of BCOR. In addition, BCOR-RARA associated with BCL6. RXR recruitment is a critical determinant of transforming potential of oligomeric RARA fusion proteins. To investigate how BCOR-RARA associates with RARE in vitro, we performed EMSA. These results showed that BCOR-RARA/RXRA complex associates with RARE in an alternative manner compared to RARA and PML-RARA. Deregulation of RARA transcriptional activations has a central role in pathogenesis of APL. Therefore, we evaluated ATRA-induced transcriptional activation of 4× RAREs with a reporter assay in HepG2 cells. Without ATRA, BCOR-RARA repressed the reporter activity. With addition of ATRA, BCOR-RARA induced transcriptional activation very weakly. Subsequently, we evaluated dominant-negative effects of the samples in the RARA/RXRA pathway. In contrast to BCOR, BCOR-RARA clearly inhibited ATRA-induced RARA transcriptional activation as well as PML-RARA. Furthermore, we asked which domains are sufficient for the dominant-negative effects with the deletion mutants. The results indicated that the region spanning from 999 to 1,409 aa of BCOR-RARA has pivotal roles in the dominant-negative effects. Correct protein function is highly dependent on intracellular localization. To investigate subcellular localization of BCOR-RARA, we performed immunofluorescence analysis in 293T cells. In BCOR-RARA-expressing cells, BCOR-RARA localized as two patterns; (I) diffusely in the nucleus as well as PML-RARA in 82% of the cells, (II) diffusely in the nucleus and aggregately in the cytoplasm in 18% of the cells. The subcellular localization of BCOR-RARA was clearly distinguishable from the punctuate pattern as shown in the nucleus of BCOR-expressing cells. Moreover, co-immunofluorescence analysis between BCOR-RARA and BCL6 indicated that the subcellular localization of BCOR-RARA/BCL6 is distinct from BCOR/BCL6. BCOR-RARA was found to possess common features with other RARA fusion proteins. These included: (I) the same break point in RARA cDNA; (II) self-association; (III) RXRA is necessary for BCOR-RARA to associate with the RARA responsive element; (IV) action in a dominant-negative manner on RARA transcriptional activation; (V) aberrant subcellular relocalization. It should be noted that there was no intact BCOR found in the 45,-Y,t(X;17)(p11;q12) APL cells because they featured only a rearranged × chromosome. These results highlight essential features of pathogenesis in APL in more detail. BCOR appears to be involved not only in human congenital diseases but also in a human cancer. Disclosures: No relevant conflicts of interest to declare.
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Redner, RL, EA Rush, S. Faas, WA Rudert, and SJ Corey. "The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion." Blood 87, no. 3 (February 1, 1996): 882–86. http://dx.doi.org/10.1182/blood.v87.3.882.bloodjournal873882.

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We have studied an acute promyelocytic leukemia (APL) patient with a variant t(5;17)(q32;q12). This translocation fuses the gene for the nucleolar phosphoprotein nucleophosmin (NPM) to the retinoic acid receptor alpha (RARA). Two alternatively spliced transcripts are expressed, which differ in 129 bases immediately upstream of the RARA sequence. The NPM sequences contained in the shorter NPM-RAR cDNA are identical to the NPM sequences contained in the NPM-ALK fusion gene expressed in t(2;5) lymphomas. The RARA sequences are the same as the RARA sequences found in the PML-RAR and PLZF-RAR fusion seen in t(15;17) and t(11;17) APL, respectively. Both NPM-RAR transcripts fuse NPM and RARA sequence in the same reading frame, to generate translation products of 57 kD and 62 kD. Both NPM-RAR proteins are expressed in the patient's leukemic cells, along with wild-type RARA derived from the uninvolved allele. In transcriptional assays using a retinoic acid response element reporter construct, both NPM-RAR fusion proteins act as retinoic acid-dependent transcriptional activators. This case defines a third class of APL rearrangements, all of which generate fusion proteins of RARA.
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Dissertations / Theses on the topic "Variant rara"

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Muiños, Gimeno Margarita. "Analysis of genetic variation in microrna-mediated regulation and the susceptibility to anxiety disorders." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7192.

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We have investigated genetic variation in microRNA-mediated regulation as a susceptibility factor for anxiety disorders following two different approaches. We first studied two isoforms of the candidate gene NTRK3 by re-sequencing its different 3'UTRs in patients with Panic (PD) and Obsessive Compulsive disorders (OCD) as well as controls. Two rare variants that altered microRNA-mediated regulation were identified in PD. Conversely, association of a common SNP with OCD hoarding subtype was found. Moreover, we have also studied a possible involvement of microRNAs in anxiety disorders. Consequently, we have analysed the genomic organisation and genetic variation of miRNA-containing regions to construct a panel of SNPs for association analysis. Case-control studies revealed several associations. However, it is worth remarking the associations of miR-22 and miR-488 with PD; two microRNAs for which functional assays and transcriptome analysis after microRNA overexpression showed significant repression of a subset of genes involved in physiological pathways linked to PD development.
Hem investigat la variació genètica a la regulació mediada per microRNAs com a factors de susceptibilitat pels trastorns d'ansietat seguint dues aproximacions diferents. Primer vam estudiar dues isoformes del gen candidat NTRK3 mitjançant la reseqüenciació dels seus diferents 3'UTRs a pacients de pànic (TP), a pacients amb trastorn obsessiu compulsiu (TOC) i a controls. Dues variants rares que alteren la regulació mediada per microRNAs foren identificades per TP. D'altra banda, es trobà associació d'un SNP comú amb el subtipus acumulador de TOC. A més, també hem estudiat la possible implicació dels microRNAs als trastorns d'ansietat. Conseqüentment, hem analitzat l'organització genòmica i la variació genètica a regions que contenen microRNAs per construir un panell d'SNPs per fer anàlisis d'associació. Els estudis cas-control van revelar algunes associacions. Tanmateix, val la pena destacar les associacions del miR-22 i el miR-488 amb TP; dos microRNAs pels quals assajos funcionals i anàlisis de transcriptoma després de la seva sobreexpressió han mostrat una repressió significativa d'un grup de gens implicats en vies fisiològiques lligades al desenvolupament del TP.
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Bhatia, Gaurav. "Rare variant analysis for common diseases." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p1467448.

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Thesis (M.S.)--University of California, San Diego, 2009.
Title from first page of PDF file (viewed August 25, 2009). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 20-23).
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Alshahrani, Mohammed Nasser D. "Statistical methods for rare variant association." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/22436/.

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Deoxyribonucleic acid (DNA) sequencing allows researchers to conduct more complete assessments of low-frequency and rare genetic variants. In anticipation of the availability of next-generation sequencing data, there is increasing interest in investigating associations between complex traits and rare variants (RVs). In contrast to association studies of common variants (CVs), due to the low frequencies of RVs, common wisdom suggests that existing statistical tests for CVs might not work, motivating the recent development of several new tests that analyze RVs, most of which are based on the idea of pooling/collapsing RVs. Genome-wide association studies (GWAS) based on common SNPs gained more attention in the last few years and have been regularly used to examine complex genetic compositions of diseases and quantitative traits. GWASs have not discovered everything associated with diseases and genetic variations. However, recent empirical evidence has demonstrated that low-frequency and rare variants are, in fact, connected to complex diseases. This thesis will focus on the study of rare variant association. Aggregation tests, where multiple rare variants are analyzed jointly, have incorporated weighting schemes on variants. However, their power is very much dependent on the weighting scheme. I will address three topics in this thesis: the definition of rare variants and their call file (VCF) and a description of the methods that have been used in rare variant analysis. Finally, I will illustrate challenges involved in the analysis of rare variants and propose different weighting schemes for them. Therefore, since the efficiency of rare variant studies might be considerably improved by the application of an appropriate weighting scheme, choosing the proper weighting scheme is the topic of the thesis. In the following chapters, I will propose different weighting schemes, where weights are applied at the level of the variant, the individual or the cell (i.e. the individual genotype call), as well as a weighting scheme that can incorporate quality measures for variants (i.e., a quality score for variant calls) and cells (i.e., genotype quality).
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Li, Samuel. "Rare Germline Variant Contributions to Myeloid Malignancy Susceptibility." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case158654099909817.

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Wang, Sophie. "Optimizing rare variant association studies in theory and practice." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11430.

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Genome-wide association studies (GWAS) have greatly improved our understanding of the genetic basis of complex traits. However, there are two major limitations with GWAS. First, most common variants identified by GWAS individually or in combination explain only a small proportion of heritability. This raises the possibility that additional forms of genetic variation, such as rare variants, could contribute to the missing heritability. The second limitation is that GWAS typically cannot identify which genes are being affected by the associated variants. Examination of rare variants, especially those in coding regions of the genome, can help address these issues. Moreover, several studies have recently identified low-frequency variants at both known and novel loci associated with complex traits, suggesting that functionally significant rare variants exist in the human population.
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Indap, Amit R. "Discovering rare variants from populations to families." Thesis, Boston College, 2013. http://hdl.handle.net/2345/3927.

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Thesis advisor: Gabor T. Marth
Partitioning an individual's phenotype into genetic and environmental components has been a major goal of genetics since the early 20th century. Formally, the proportion of phenotypic variance attributable to genetic variation in the population is known as heritability. Genome wide association studies have explained a modest percentage of variability of complex traits by genotyping common variants. Currently, there is great interest in what role rare variants play in explaining the missing heritability of complex traits. Advances of next generation sequencing and genomic enrichment technologies over the past several years have made it feasible to re-sequence large numbers of individuals, enabling the discovery of the full spectrum of genetic variation segregating in the human population, including rare variants. The four projects that comprise my dissertation all revolve around the discovery of rare variants from next generation sequencing datasets. In my first project, I analyzed data from the exon sequencing pilot of the 1000 Genomes Project, where I discovered variants from exome capture sequencing experiments in a worldwide sample of nearly 700 individuals. My results show that the allele frequency spectrum of the dataset has an excess of rare variants. My next project demonstrated the applicability of using whole-genome amplified DNA (WGA) in capture sequencing. WGA is a method that amplifies DNA from nanogram starting amounts of template. In two separate capture experiments I compared the concordance of call sets, both at the site and genotype level, of variant calls derived from WGA and genomic DNA. WGA derived calls have excellent concordance metrics, both at the site and genotypic level, suggesting that WGA DNA can be used in lieu of genomic DNA. The results of this study have ramifications for medical sequencing experiments, where DNA stocks are a finite quantity and re-collecting samples maybe too expensive or not possible. My third project kept its focus on capture sequencing, but in a different context. Here, I analyzed sequencing data from Mendelian exome study of non-sensorineural hearing loss (NSHL). A subset of 6 individuals (5 affected, 1 unaffected) from a family of European descent were whole exome sequenced in an attempt to uncover the causative mutation responsible for the loss of hearing phenotype in the family. Previous linkage analysis uncovered a linkage region on chr12, but no mutations in previous candidate genes were found, suggesting a novel mutation segregates in the family. Using a discrete filtering approach with a minor allele frequency cutoff, I uncovered a putative causative non-synonymous mutation in a gene that encodes a transmembrane protein. The variant perfectly segregates with the phenotype in the family and is enriched in frequency in an unrelated cohort of individuals. Finally, for my last project I implemented a variant calling method for family sequencing datasets, named Pgmsnp, which incorporates Mendelian relationships of family members using a Bayesian network inference algorithm. My method has similar detection sensitivities compared to other pedigree aware callers, and increases power of detection for non-founder individuals
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology
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7

Seabra, Catarina Morais. "Rare structural variants in severe spermatogenic impairment." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/9537.

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Mestrado em Biomedicina Molecular
A azoospermia afeta aproximadamente 15% de todos os homens inférteis e é frequentemente causada por anomalias cromossómicas e microdeleções do cromossoma Y. No entanto, em aproximadamente 70% dos casos de azoospermia não-obstrutiva (NOA) as causas permanecem por identificar. Nos últimos anos, a descoberta de variantes genómicas de número de cópia (CNVs), como as causadas por deleções, revelou uma fonte de variação genómica que afecta a dosagem génica e que poderá resultar em haploinsuficiência. De facto, observa-se uma sobre-representação de CNVs raros (<1% na população), sobretudo de grandes deleções de novo, em pacientes com diferentes distúrbios do desenvolvimento, comparados com controlos saudáveis. Porém, uma possível contribuição, para a infertilidade masculina, de variantes estruturais ligados ao cromossoma X e aos autossomas foi ainda pouco explorada. Este estudo foca-se na validação de deleções encontradas apenas em pacientes inférteis, no cromossoma X e em 11p13, que contêm genes candidatos a participar na espermatogénese. Estas deleções, previamente identificadas por arrays de oligonucleótidos, de elevada densidade (Affymetrix 6.0 SNP Array), numa coorte de 171 pacientes Portugueses com disfunção severa da espermatogénese (NOA e oligozoospermia severa), foram agora confirmadas por técnicas convencionais de genética molecular. Adicionalmente, a caraterização dos locais de quebra nestas deleções foi realizada por aCGH. Ainda que não se tenham validado as deleções menos extensas (em Xq21.1, Xq25, Xp11.4, Xq22.1 e Xq26.3), confirmou-se a nulizigotia em Xq28 nestes indivíduos, que abrange genes candidatos com uma função sugestiva na espermatogénese: MAGE-A8, expresso em testículo e em alguns cancros e o microRNA hsa-miR-4330, envolvido na regulação pós-transcricional de vários genes com expressão na linha germinal. Foi ainda validada, por MLPA, uma deleção extensa num paciente infértil não-sindrómico da nossa coorte. Estes resultados apontam a haploinsuficiência de WT1 como a causa mais provável de azoospermia neste paciente, já que não foram detetadas mutações germinais no alelo restante. Mutações no gene WT1, que codifica um factor de transcrição muito conservado, crucial para o desenvolvimento e manutenção gonadal em mamíferos, geralmente interferem com a ligação desta proteína ao DNA e estão principalmente associadas a síndromes que envolvem anomalias reprodutivas. Motivados pela nossa descoberta de uma deleção de WT1 num homem infértil embora saudável, decidimos abordar a contribuição de mutações exónicas no gene WT1 para a azoospermia isolada. Testámos a hipótese de que mutações localizadas em domínios que não aqueles essenciais à ligação ao DNA pudessem resultar na disfunção não-sindrómica da espermatogénese. Assim, analisámos a sequência codificante de WT1 num subgrupo de 40 pacientes azoospérmicos. Como resultado, descrevemos uma nova variação missense c.185C>T (P130L; ENST00000332351) no primeiro exão de WT1, inserida no domínio proteico de auto-associação. A nova variante descrita deverá ter um impacto menos drástico na função da proteína WT1, comparativamente com as mutações descritas no mesmo exão até à data, as quais resultam em proteínas truncadas e fenótipos severos de disfunção gonadal, incluindo a formação de tumores renais. Estes resultados revelam novos genes candidatos a um papel na espermatogénese e sugerem que a haploinsuficiência de proteínas importantes para o desenvolvimento do sistema reprodutor masculino podem resultar em azoospermia. Estudos futuros poderão clarificar a utilidade dos nossos genes candidatos como biomarcadores da infertilidade masculina. A implementação de novos biomarcadores beneficiaria os doentes azoospérmicos através da melhoria do diagnóstico, aconselhamento genético e acompanhamento destes pacientes, podendo vir a limitar a necessidade de procedimentos invasivos.
Azoospermia affects approximately 15% of all infertile males and it is frequently caused by chromosomal abnormalities and Yq microdeletions. However, despite considerable research efforts in the last decades, in approximately 70% of the cases of non-obstructive azoospermia (NOA) the causes are yet to be identified. In the last years, the discovery of genomic copy number variants, such as those caused by deletions, revealed a source of genomic variation which impacts gene dosage and may result in haploinsufficiency. In fact, rare CNVs (<1% population), mainly large de novo deletions, are over-represented in patients with different developmental disorders, compared to healthy controls. However, a possible contribution of X-linked and autosomal structural variants to male infertility is still largely unexplored. This study focused on the validation of rare patient-specific deletions found on the X chromosome and at 11p13 of infertile patients, which harbor candidate spermatogenesis genes. These deletions had been previously identified by high density oligonucleotide arrays (Affymetrix 6.0 SNP Array), in a cohort of 171 Portuguese patients with severe spermatogenic impairment (non-obstructive azoospermia and severe oligozoospermia) and were now confirmed by conventional molecular genetics techniques. Additionally, breakpoint characterization was carried out by aCGH. In fact, even though the smaller deletions (at Xq21.1, Xq25, Xp11.4, Xq22.1 and Xq26.3) were not validated, we confirmed nullizygosity at Xq28 in two patients, spanning either MAGE-A8, a known cancer-testis antigen, or hsa-miR-4330, a microRNA involved in post-transcription regulation, both with a suggestive role in spermatogenesis pathways. We have also validated by MLPA a large deletion at 11p13, in a non-syndromic infertile patient from our cohort. These results support WT1 haploinsufficiency as the likely cause of azoospermia in this patient, as no other germline mutations were detected in the remaining WT1 copy. Mutations in WT1, an evolutionarily conserved transcription factor crucial for gonadal development and maintenance in mammals, typically interfere with the DNA-binding properties of the protein and are mainly associated with syndromes involving reproductive abnormalities. Motivated by our finding of a WT1 deletion in an infertile but otherwise healthy man we addressed the contribution of WT1 exonic mutations to isolated azoospermia. We reasoned that mutations located in domains not essential for DNA binding could result in non-syndromic spermatogenic impairment. Thus, we analyzed the WT1 coding sequence in a subgroup of 40 azoospermic patients. As a result of the exon screening, we report a novel c.185C>T (P130L; ENST00000332351) WT1 missense variant on exon 1, within the protein self-association domain. While all exon 1 mutations as yet reported result in truncated proteins and severe phenotypes, including the formation of renal tumors, this novel variant is expected to have a milder impact on WT1 function. These results reveal new candidate genes for a role in spermatogenesis and suggest that haploinsufficiency of proteins important for the development of the male reproductive system can lead to azoospermia. Further studies will clarify the utility of our candidate genes as biomarkers of male infertility. The implementation of new biomarkers would benefit azoospermic men by improving diagnosis, genetic counseling and patient care, eventually limiting the need for invasive procedures.
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Weir, Gregory A. "Investigating rare genetic variants in common migraine." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:2aad341d-91fb-4ee8-8c55-ddd81b33247e.

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Migraine is a highly prevalent headache disorder imposing a significant burden of disability on human health worldwide. The headache is believed to arise from activation of trigeminal pain pathways, with CNS regions also playing an integral role in attack initiation and progression. Recent genetic associations have been made, but there is a need to convert these into relevant experimental models to study underlying disease mechanisms. Herein, I detail functional analysis of two deleterious variants in the genes KCNK18 and SLC12A3, that segregate with migraine with aura in one large pedigree. Gene function has been studied in a range of cell models, from heterologous expression systems and primary neuronal cultures, to Induced Pluripotent Stem (iPS) cell-derived nociceptors. In this context, the protein products of KCNK18 and SLC12A3 have been shown to modulate parameters of neuronal excitability, including baseline membrane properties and firing patterns. Migraine attacks are not wholly attributable to perturbations in peripheral pathways. I have shown that these genes are also expressed within the CNS in a small number of discreet regions, suggesting a possible role in central processing. Utilizing recently defined genetic variants and physiological cell- based models, will provide a platform for mechanistic insights into migraine pathogenesis and allow for the development of drug screening assays for new migraine therapies.
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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.

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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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Kleinecke, Mariana [Verfasser], Jeanette [Akademischer Betreuer] Erdmann, and Hauke [Gutachter] Busch. "Rare variants and coronary artery disease : Seltene Varianten und koronare Herzerkrankung / Mariana Kleinecke ; Gutachter: Hauke Busch ; Akademischer Betreuer: Jeanette Erdmann." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2020. http://d-nb.info/1207954705/34.

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Books on the topic "Variant rara"

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Jentz, Thomas L. Germany's Panther tank: The quest for supremacy : development, modifications, rare variants characteristics, combat accounts. Atglen, PA: Schiffer Pub., 1995.

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Jackson, David Paul, and Khro-phu lo-tsā-ba. Two biographies of Śākyaśrībhadra: The eulogy by Khro-phu lo-tsā-ba and its commentary by Bsod-nams-dpal-Bzang-po ; texts and variants from two rare exemplars preserved in the Bihar Research Society, Patna. Stuttgart: F. Steiner, 1990.

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Syrris, Petros, and Alexandros Protonotarios. Arrhythmogenic right ventricular cardiomyopathy: genetics. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0359.

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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of the heart muscle which is typically inherited in an autosomal dominant manner. It is believed to be familial in over 50% of cases. A recessive mode of inheritance has also been reported in syndromic cases with cardiocutaneous features. The classic form of the disorder is considered to be ‘a disease of the desmosome’ as pathogenic variants have been identified in five genes encoding key desmosomal proteins: plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. Mutations in these genes account for 30–50% of ARVC cases. A further eight non-desmosomal genes have also been implicated in the pathogenesis of the disorder but only account for rare cases. Studies of patients with ARVC-associated gene mutations have revealed marked genetic heterogeneity and very limited genotype–phenotype correlation. Disease expression often varies significantly amongst individuals carrying the same mutation. It has been proposed that the presence of more than one sequence variant is required to determine overt clinical disease and patients with multiple variants have a more severe phenotype compared to single variant carriers. Identification of a potentially pathogenic variant comprises a major criterion in the diagnosis of ARVC but informative integration of genetic testing into clinical practice remains challenging. Gene testing should be used to identify asymptomatic family members at risk and only aids diagnosis in cases of high suspicion for ARVC, along with other evident features of the disease already present. However, genetic findings should be used with caution in clinical practice and their interpretation must be performed in expert centres.
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Langley, Kate. ADHD genetics. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198739258.003.0003.

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This chapter reviews the evidence suggesting that there is a strong genetic component to ADHD and the efforts to identify the specific genetic factors that might be involved. It discusses the different types of genetic contributions, from common to rare variants, and the evidence that these are involved in the aetiology of the disorder. An overview of the methodological strategies employed, including genome-wide association studies (GWAS), polygenic risk score, and copy number variant (CNV) analyses, is undertaken, as well as discussion of the strengths and pitfalls of such work. The contradictory findings in the field and controversies that arise as a result are also explored. Finally, this chapter considers how the heritability of ADHD and specific genetic factors involved need to be examined in the context of clinical factors such as comorbidity and how these factors affect investigations into the genetics of ADHD.
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Penney, Kathryn L., Kyriaki Michailidou, Deanna Alexis Carere, Chenan Zhang, Brandon Pierce, Sara Lindström, and Peter Kraft. Genetic Epidemiology of Cancer. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190238667.003.0005.

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Chapter 5 reviews epidemiologic studies conducted to identify germline (inherited) susceptibility loci. These studies can involve associations observed within high-risk family pedigrees or in large studies of unrelated individuals. The chapter reviews the methods used to estimate the aggregate contribution of inherited genetic susceptibility and to identify specific genetic loci associated with risk. Although there is considerable variability across cancers, most cancers exhibit familial clustering, driven in part by a small number of known rare variants with large relative risks and a larger number of common variants with modest relative risks. The chapter discusses the implications of these findings for clinical care, public health, and tumor biology. It closes with a discussion of open questions, most notably the puzzle of “missing heritability”: the fact that—despite tremendous advances—multiple lines of evidence suggest that most specific risk variants, both rare and common, have yet to be discovered.
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Beattie, R. Mark, Anil Dhawan, and John W.L. Puntis. α‎1-antitrypsin deficiency. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569862.003.0049.

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Clinical features 354Management 355Liver disease in other forms of α‎1-AT deficiency 355α‎1-Antitrypsin (α‎1-AT) is a 55 kD glycoprotein produced predominantly by hepatocytes, alveolar macrophages and intestinal endothelial cells. It acts as a protease inhibitor during an acute-phase response. It can be electrophoretically differentiated into four main variants: PiM (normal), PiZ, PiS, and Pi Null (abnormal). There are >80 other rare, clinically irrelevant, variants. ...
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Charney, Alexander, and Pamela Sklar. Genetics of Schizophrenia and Bipolar Disorder. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0013.

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Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. There is now convincing genetic evidence that indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, and there is evidence for polygenicity. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder.
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Bentham, James R. The genetics of congenital heart disease. Edited by José Maria Pérez-Pomares, Robert G. Kelly, Maurice van den Hoff, José Luis de la Pompa, David Sedmera, Cristina Basso, and Deborah Henderson. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198757269.003.0022.

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Congenital heart disease (CHD) is defined as a structural cardiac malformation resulting from an abnormality of development; 8% of CHD is inherited in a Mendelian fashion and 12% results from chromosomal imbalance. Recurrence risk and new research suggest that even the remaining 80% of patients without an identifiable familial or syndromic basis for disease may have an identifiable genetic cause. The potential to understand these mechanisms is increasing with the advent of new sequencing techniques which have identified multiple or single rare variants and/or copy number variants clustering in cardiac developmental genes as well as common variants that may also contribute to disease, for example by altering metabolic pathways. Work in model organisms such as mouse and zebrafish has been pivotal in identifying CHD candidate genes. Future challenges involve translating the discoveries made in mouse models to human CHD genetics and manipulating potentially protective pathways to prevent disease.
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Rucker, James J. H., and Peter McGuffin. Copy Number Variation in Neuropsychiatric Disorders. Edited by Turhan Canli. Oxford University Press, 2013. http://dx.doi.org/10.1093/oxfordhb/9780199753888.013.005.

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It has long been known that the human genome is subject to deletion and duplication of genetic material by various molecular mechanisms. Until recently, such events were assumed to be relatively rare phenomena. It is now known that submicroscopic deletions or duplications calledcopy number variants(CNVs) are a major source of genomic variation. Rare CNVs (defined as occurring in less than 1 percent of the population) have been implicated in schizophrenia and autism. Measured in terms of odds ratios, individual CNVs have been shown to have large effects, some increasing the risk of disorder several-fold. But they are incompletely penetrant, no one CNV is either necessary or sufficient to cause the disorder. The findings are less clear-cut with bipolar disorder but, here, too, rare CNVs probably play a role. In unipolar depression, initial evidence suggests an overall increase in rare CNVs that disrupt exons, the coding regions of genes.
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West, Michael, and Gabor Linthorst. Fabry Disease. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0049.

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Fabry disease was initially believed to be a very rare disorder, but an increase in prevalence following screening studies revealed that it may be more frequent in a less severe (nonclassical) variant. The adult physician can encounter both phenotypes: classical disease arising in childhood, or after establishing the diagnosis in an adult male. The nonclassical phenotype is usually diagnosed after additional investigations in a patient with renal disease or left ventricular hypertrophy (LVH) of unknown origin. Enzyme replacement therapy (ERT) appears to have a modest effect in Fabry disease, and many challenges remain both in understanding the pathophysiology and natural history as well as in improving patient outcomes.
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Book chapters on the topic "Variant rara"

1

Margaritescu, Irina, and A. Doru Chirita. "Rare Variants of Mycosis Fungoides: Granulomatous Slack Skin Variant of Mycosis Fungoides." In Rare Malignant Skin Tumors, 267–70. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-2023-5_60.

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Mahajan, Anubha, and Neil Robertson. "Rare Variant Quality Control." In Assessing Rare Variation in Complex Traits, 33–43. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2824-8_3.

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Feng, Tao, and Xiaofeng Zhu. "Detecting Rare Variants." In Methods in Molecular Biology, 453–64. Totowa, NJ: Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-555-8_24.

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Fromer, Menachem, and Shaun Purcell. "Rare Structural Variants." In Assessing Rare Variation in Complex Traits, 45–56. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2824-8_4.

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El-Fishawy, Paul. "Common Disease-Rare Variant Hypothesis." In Encyclopedia of Autism Spectrum Disorders, 720–22. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4419-1698-3_1997.

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El-Fishawy, Paul. "Common Disease-Rare Variant Hypothesis." In Encyclopedia of Autism Spectrum Disorders, 1083–84. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-319-91280-6_1997.

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Ouyang, Weiwei, Xiaofeng Zhu, and Huaizhen Qin. "Detecting Multiethnic Rare Variants." In Methods in Molecular Biology, 527–38. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-7274-6_26.

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Greenwood, Celia M. T., ChangJiang Xu, and Antonio Ciampi. "Significance Thresholds for Rare Variant Signals." In Assessing Rare Variation in Complex Traits, 169–83. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2824-8_12.

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Rivas, Manuel A., and Loukas Moutsianas. "Power of Rare Variant Aggregate Tests." In Assessing Rare Variation in Complex Traits, 185–99. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2824-8_13.

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Feng, Tao, and Xiaofeng Zhu. "Rare Variant Analysis in Unrelated Individuals." In Applied Computational Genomics, 27–44. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-13-1071-3_4.

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Conference papers on the topic "Variant rara"

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Shahzadi, A., D. Kumar, Z. Khan, M. Bachan, and R. Siegel. "A Rare Variant of Eagle's Syndrome." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a2999.

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MOORE, CARRIE B., JOHN R. WALLACE, ALEX T. FRASE, SARAH A. PENDERGRASS, and MARYLYN D. RITCHIE. "USING BIOBIN TO EXPLORE RARE VARIANT POPULATION STRATIFICATION." In Proceedings of the Pacific Symposium. WORLD SCIENTIFIC, 2012. http://dx.doi.org/10.1142/9789814447973_0033.

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Gadela, N. V., M. Paravathaneni, T. Gadela, D. Drekolias, E. Wasserman, R. Shaikh, and N. Perosevic. "Yamaguchi Syndrome- A Rare Variant of Hypertrophic Obstructive Cardiomyopathy." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a3001.

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MARTIN, ALICIA R., GERARD TSE, CARLOS D. BUSTAMANTE, and EIMEAR E. KENNY. "IMPUTATION-BASED ASSESSMENT OF NEXT GENERATION RARE EXOME VARIANT ARRAYS." In Proceedings of the Pacific Symposium. WORLD SCIENTIFIC, 2013. http://dx.doi.org/10.1142/9789814583220_0024.

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Saeed, M., A. Gohar, A. Shahzadi, M. Khan, and M. Siuba. "Miller Fischer Syndrome; A Rare Variant of Guillian Barre Syndrome." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a2929.

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Karopoulou, E., N. Koufopoulos, S. Kokkali, A. Arapaki, K. Strataki, S. Polykalas, and D. Papatheodorou. "EP717 Challenging diagnosis: plexiform tumorlet. A rare variant of uterine leiomyoma." In ESGO Annual Meeting Abstracts. BMJ Publishing Group Ltd, 2019. http://dx.doi.org/10.1136/ijgc-2019-esgo.771.

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Stakhurlova, L. D., and I. D. Svistova. "Reaction of micromycetes of leached chernozem on the application of different forms of nitrogen fertilizers." In РАЦИОНАЛЬНОЕ ИСПОЛЬЗОВАНИЕ ПРИРОДНЫХ РЕСУРСОВ В АГРОЦЕНОЗАХ. Federal State Budget Scientific Institution “Research Institute of Agriculture of Crimea”, 2020. http://dx.doi.org/10.33952/2542-0720-15.05.2020.34.

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Application of nitrogen fertilizers did not significantly affect the number of micromycetes. The restructuring of the species structure of the mycobiome did not exceed the adaptive zone of “stress” – a change in the frequency of occurrence of typical species. Typical types of leached chernozem micromycetes include deuteromycetes of the genera Aspergillus, Penicillium, Trichoderma, Gliocladium, Humicola, Fusarium, zygomycetes (genus Rhizopus), ascomycetes (genera Thalaromyces, Chaetomium). On average, the density of dominant species of micromycetes increased by 20 %, which indicates the development of the “dominance concentration” of typical species and a decrease in the share of rare and random species of fungi in the mycocomplex. In the experiment variants, the density of Penicillium daleae, P. funiculosum, Fusarium solani, and Aspergillus ustus species increased compared to control. These types of micromycetes are toxigenic and synthesize broad-spectrum mycotoxins (fungicidal, antibiotic, and phytotoxic). As a result, the phytotoxic activity of the soil increased to 7 and 20 % (native soil) and to 19-34 % (initiated microbial community). More pronounced changes were observed in the variant with ammonium sulfate. Thus, nitrogen fertilizers at a dose of N90 cause a “stress” reaction of the mycobiome, an increase in the share of toxigenic species and phytotoxic activity of leached chernozem. With long-term systematic use of nitrogen fertilizers, even in medium doses, it is possible to reduce the potential fertility of chernozems.
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Craig, Daniel J., Mazzin Elsamaloty, Thomas M. Blomquist, Erin L. Crawford, and James C. Willey. "Abstract 2222: Using rare variants to characterize lung cancer risk." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-2222.

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Diskin, Sharon J., Mario Capasso, Maura Diamond, Kristopher Bosse, Hakon Hakonarson, Marcella Devoto, and John M. Maris. "Abstract 3811: Rare variants at 16p11.2 and withinTP53influence neuroblastoma susceptibility." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-3811.

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Yufeng Shen, Yee Him Cheung, Shuang Wang, and I. Pe'er. "A parametric Bayesian method to test the association of rare variants." In 2011 IEEE International Conference on Bioinformatics and Biomedicine Workshops (BIBMW). IEEE, 2011. http://dx.doi.org/10.1109/bibmw.2011.6112366.

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