Improved Splice Site Detection in Genie

Reese, Martin G.; Eeckman, Frank H.; Kulp, David; Haussler, David

doi:10.1089/cmb.1997.4.311

Cited by 1,454 publications

(846 citation statements)

References 17 publications

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“…The splice prediction tools used were SpliceSiteFinder‐like (Zhang 1998), MaxEntScan (Yeo and Burge 2004), NNSPLICE (Reese et al. 1997), GeneSplicer (Pertea et al. 2001), and Human Splicing Finder (Desmet et al.…”

Section: Methodsmentioning

confidence: 99%

Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations

Sjursen

McPhillips²,

Scott

et al. 2016

Molec Gen & Gen Med

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BackgroundLynch syndrome, the most frequent hereditary colorectal cancer syndrome, is caused by defects in mismatch repair genes. Genetic testing is important in order to identify mutation carriers who can benefit from intensive surveillance programs. One of the challenges with genetic testing is the interpretation of pathogenicity of detected DNA variants. The aim of this study was to investigate all putative pathogenic variants tested for at the Division of Molecular Medicine, Pathology North, in Newcastle, Australia, to establish whether previous variant classification is in accordance with that recently performed in the InSiGHT collaboration.MethodsPrediction programs and available literature were used to classify new variants or variants without classification.ResultsWe identified 333 mutation positive families, in which 211 different putative pathogenic mismatch repair mutations were found. Most variants with an InSiGHT classification (141 out of 146) were in accordance with our classification. Five variants were discordant, of which one can definitively be reclassified according to the InSiGHT scheme as class 5. Sixty‐four variants had not been classified by InSiGHT, of whom 55 have not been previously reported.ConclusionIn conclusion, we found that our classifications were mostly in accordance with the InSiGHT scheme. In addition to already known MMR mutations, we have also presented 55 novel pathogenic or putative pathogenic mutations.

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Section: Methodsmentioning

confidence: 99%

Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations

Sjursen

McPhillips²,

Scott

et al. 2016

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…The possible effects on mRNA were evaluated with tools including splice site prediction by neural network (www.fruitfly.org/seq_tools/splice.html) (Reese et al. 1997), the Human Splicing Finder (HSF; http:www.umd.be/HSF/) (Desmet et al. 2009) and exonic splicing enhancer (ESE) Finder (http://rulai.cshl.edu/cgibin/tools/ESE3/esefinder.cgi?process=home) (Cartegni et al.…”

Section: Methodsmentioning

confidence: 99%

126 novel mutations in Italian patients with neurofibromatosis type 1

Bianchessi¹,

Morosini²,

Saletti³

et al. 2015

Molec Gen & Gen Med

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Genetic analysis of Neurofibromatosis type 1 (NF1) may facilitate the identification of patients in early phases of the disease. Here, we present an overview of our diagnostic research spanning the last 11 years, with a focus on the description of 225 NF1 mutations, 126 of which are novel, found in a series of 607 patients (513 unrelated) in Italy. Between 2003 and 2013, 443 unrelated patients were profiled by denaturing high pressure liquid chromatography (DHPLC) analysis of 60 amplicons derived from genomic NF1 DNA and subsequent sequencing of heterozygotic PCR products. In addition, a subset of patients was studied by multiplex ligation‐dependent probe amplification (MLPA) to identify any duplications, large deletions or microdeletions present at the locus. Over the last year, 70 unrelated patients were investigated by MLPA and sequencing of 22 amplicons spanning the entire NF1 cDNA. Mutations were found in 70% of the 293 patients studied by DHPLC, thereby fulfilling the NIH criterion for the clinical diagnosis of NF1 (detection rate: 70%); furthermore, 87% of the patients studied by RNA sequencing were genetically characterized. Mutations were also found in 36 of the 159 patients not fulfilling the NIH clinical criteria. We confirmed a higher incidence of intellectual disability in patients harboring microdeletion type 1 and observed a correlation between a mild phenotype and the small deletion c.2970_2972delAAT or the missense alteration in amino acid residue 1809 (p.Arg1809Cys). These data support the use of RNA‐based methods for genetic analysis and provide novel information for improving the management of symptoms in oligosymptomatic patients.

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“…To analyse the impact of BRCA2 c.7802A4G variant on splicing, we used the Alamut decision-support software (Interactive Biosoftware, Rouen, France) that includes the splice site prediction by neural network (NNSplice), 13 splice site finder, 14 Max-EntScan, 15 ESE finder 16 and human splicing finder 17 algorithms. This software also includes three protein-function prediction tools: Align-GVGD, (http://agvgd.iarc.fr/), SIFT (http://sift.jcvi.org/), and PolyPhen-2 http://genetics.bwh.harvard.edu/pph2/.…”

Section: In Silico Prediction Toolsmentioning

confidence: 99%

Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene

et al. 2013

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Fanconi anaemia (FA) is characterized by progressive bone marrow failure, congenital anomalies, and predisposition to malignancy. In a minority of cases, FA results from biallelic FANCD1/BRCA2 mutations that are associated with early-onset leukaemia and solid tumours. Here, we describe the clinical and molecular features of a remarkable family presenting with multiple primary colorectal cancers (CRCs) without detectable mutations in genes involved in the Mendelian predisposition to CRCs. We unexpectedly identified, despite the absence of clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2 corresponding to a frameshift alteration (c.1845_1846delCT, p.Asn615Lysfs*6) and a missense mutation (c.7802A4G, p.Tyr2601Cys). The diagnosis of FA was confirmed by the chromosomal analysis of lymphocytes. Reverse transcriptase (RT)-PCR analysis revealed that the c.7802A4G BRCA2 variation was in fact a splicing mutation that creates an aberrant splicing donor site and results partly into an aberrant transcript encoding a truncated protein (p.Tyr2601Trpfs*46). The atypical FA phenotype observed within this family was probably explained by the residual amount of BRCA2 with the point mutation c.7802A4G in the patients harbouring the biallelic FANCD1/BRCA2 mutations. Although this report is based in a single family, it suggests that CRCs may be part of the tumour spectrum associated with FANCD1/BRCA2 biallelic mutations and that the presence of such mutations should be considered in families with CRCs, even in the absence of cardinal features of FA.

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Improved Splice Site Detection in Genie

Cited by 1,454 publications

References 17 publications

Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations

Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations

126 novel mutations in Italian patients with neurofibromatosis type 1

Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene

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