Improved splice site detection in Genie

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

doi:10.1145/267521.267766

Cited by 858 publications

(545 citation statements)

References 19 publications

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“…SIFT predicts substitutions with scores less than 0.05 as deleterious, and PolyPhen-2 scores are evaluated as 0.000 (most probably benign) to 0.999 (most probably damaging). The effect of potential splice site variations was evaluated by "Human Splicing Finder" (http://www.umd.be/HSF/) (Desmet et al 2009) and "Splice Site Prediction by Neural Network" (http://www.fruitfly.org/seq_tools/splice.html) (Reese et al 1997) tools.…”

Section: Brca1/2 Mutation Analysismentioning

confidence: 99%

Evaluation of BRCA1/2 mutational status among German and Austrian women with triple-negative breast cancer

Muendlein

Rohde

Gasser

et al. 2015

J Cancer Res Clin Oncol

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Section: Brca1/2 Mutation Analysismentioning

confidence: 99%

Evaluation of BRCA1/2 mutational status among German and Austrian women with triple-negative breast cancer

Muendlein

Rohde

Gasser

et al. 2015

J Cancer Res Clin Oncol

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“…2b) using five Web-based programs: ESEfinder 3.0 (http://rulai.cshl.edu/cgi-bin/tools/ESE3/ esefinder.cgi?process=home) (Cartegni et al 2003), ESRsearch (http://ast.bioinfo.tau.ac.il/) (Goren et al 2006), FAS-ESS (http://genes.mit.edu/fas-ess/) , PESXs (http://cubweb.biology.columbia.edu/pesx/) (Zhang and Chasin 2004;Zhang et al 2005), and RESCUE-ESE (http://genes.mit.edu/burgelab/rescue-ese/) (Fairbrother et al 2002). We also predicted the effects of the mutations on splice site strength of the 18 sequence variants using two Web-based programs: the NetGene2 Server (http://www.cbs.dtu.dk/services/NetGene2/) (Brunak et al 1991;Hebsgaard et al 1996) and the Splice Site Prediction by Neural Network (http://www.fruitfly.org/ seq_tools/splice.html) (Reese et al 1997). …”

Section: Sequence Analysis Of Col1a1mentioning

confidence: 99%

Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8

et al. 2011

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Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2. We identified a dominant missense mutation, c.3235G>A in COL1A1 exon 45 predicting p.G1079S, in a Japanese family with mild OI. As mutations in exon 45 exhibit mild to lethal phenotypes, we tested if disruption of an exonic splicing cis-element determines the clinical phenotype, but detected no such mutations. In the Japanese family, juvenile-onset hyperuricemia cosegregated with OI, but not in the previously reported Italian and Canadian families with c.3235G>A. After confirming lack of a founder haplotype in three families, we analyzed PRPSAP1 and PRPSAP2 as candidate genes for hyperuricemia on chr 17 where COL1A1 is located, but found no mutation. We next resequenced the whole exomes of two siblings in the Japanese family and identified variable numbers of previously reported hyperuricemia-associated SNPs in ABCG2 and SLC22A12. The same SNPs, however, were also detected in normouricemic individuals in three families. We then identified two missense SNVs in ZPBP2 and GPATCH8 on chromosome 17 that cosegregated with hyperuricemia in the Japanese family. ZPBP2 p.T69I was at the non-conserved region and was predicted to be benign by in silico analysis, whereas GPATCH8 p.A979P was at a highly conserved region and was predicted to be deleterious, which made p.A979P a conceivable candidate for juvenile-onset hyperuricemia. GPATCH8 is only 5.8 Mbp distant from COL1A1 and encodes a protein harboring an RNA-processing domain and a zinc finger domain, but the molecular functions have not been elucidated to date.

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“…The sequences from dog (Canis familiaris ENSCAFT00000003421), chicken (Gallus gallus ENSGALG00000016679) and frog (Xenopus Tropicalis ENSXETP00000046871) were obtained using Ensemble. For the prediction of splice sites we used: Neural Network Splice Site Prediction http://www.fruitfly.org/seq_tools/splice.html (Reese et al 1997); CBS NetGene 2 http://www.cbs.dtu.dk/ services/NetGene2/ (Brunak et al 1990); Splice Site Finder http://www.genet.sickkids.on.ca/$ali/splicesitefinder.html (Senapathy et al 1990). Exon numbering according to Onuchic et al (2002).…”

Section: Creation and Analysis Of Multiple Sequence Alignmentmentioning

confidence: 99%

“…Four strongly predicted splice site mutations have been observed involving the 100% conserved nucleotides of the splice site consensus sequences (Table 3). In addition, all missense variants were analyzed for potential splice site effects using splice predict software (Brunak 1990;Reese 1997;Senapathy 1990). Three missense mutations were predicted to alter splicing.…”

Section: Sequencingmentioning

confidence: 99%

Analysis of missense variants in the PKHD1-gene in patients with autosomal recessive polycystic kidney disease (ARPKD)

et al. 2005

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Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease characterized by enlarged kidneys and congenital hepatic fibrosis. Given the poor prognosis for the majority of children with the severe perinatal ARPKD phenotype, there is a regular request for prenatal testing. ARPKD is caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene, which consists of 86 exons that are variably assembled into a number of alternatively spliced transcripts. The longest transcript, comprising 67 exons, encodes the protein fibrocystin/polyductin. We have set up mutation analysis by direct sequencing of these 67 exons. In 39 mainly Dutch families we identified: 11 nonsense mutations, 15 deletions/insertions, 5 splice site mutations, and 39 missense mutations. To classify missense variants we combined evolutionary conservation, using the human, chimpanzee, dog, mouse, chicken and frog Pkhd1 sequences, with the Grantham score for chemical differences. Thirty-three missense mutations were considered pathogenic and seven were classified as rare, probably pathogenic variants. In addition to sequence analysis, multiplex ligation-dependent probe amplification (MLPA) was used to identify multiple exon deletions. However, no large deletions in the PKHD1 gene were identified. In 31 index patients two mutations were found, in 6 patients one mutation was found, leading to a mutation detection rate of 87%. The analysis of amino acid conservation as well as applying the Grantham score for chemical differences allowed us to determine the pathogeneity for nearly all new missense mutations and thus proved to be useful tools to classify missense variants.

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Improved splice site detection in Genie

Cited by 858 publications

References 19 publications

Evaluation of BRCA1/2 mutational status among German and Austrian women with triple-negative breast cancer

Evaluation of BRCA1/2 mutational status among German and Austrian women with triple-negative breast cancer

Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8

Analysis of missense variants in the PKHD1-gene in patients with autosomal recessive polycystic kidney disease (ARPKD)

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