The Experts below are selected from a list of 126963 Experts worldwide ranked by ideXlab platform
Robert A Hegele - One of the best experts on this subject based on the ideXlab platform.
-
homozygous missense mutation g56r in glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 gpi hbp1 in two siblings with fasting chylomicronemia mim 144650
Lipids in Health and Disease, 2007Co-Authors: Jian Wang, Robert A HegeleAbstract:Background Mice with a deleted Gpihbp1 gene encoding glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) develop severe chylomicronemia. We screened the coding regions of the human homologue – GPIHBP1 – from the genomic DNA of 160 unrelated adults with fasting chylomicronemia and plasma triglycerides >10 mmol/L, each of whom had Normal Sequence of the LPL and APOC2 genes.
Naomi Kondo - One of the best experts on this subject based on the ideXlab platform.
-
a novel single base substitution c 1124a g that activates a 5 base upstream cryptic splice donor site within exon 11 in the human mitochondrial acetoacetyl coa thiolase gene
Molecular Genetics and Metabolism, 2008Co-Authors: Toshiyuki Fukao, Avihu Boneh, Yusuke Aoki, Naomi KondoAbstract:Abstract Most mutations related to aberrant splicing occur in conserved splice acceptor and donor sites. Some exonic mutations also affect splicing. We identified and characterized a point mutation (c.1124A>G) in an Australian patient (GK43) with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. GK43 is a homozygote of c.1124A>G, which activates a cryptic splice donor site 5 bases upstream from c.1124A>G within exon 11, causing aberrant splicing in most transcripts. The aberrant splicing results in c.1120–1163 (44-base) deletion, causing a frameshift in T2 mRNA. A mini-gene splicing experiment confirmed that the c.1124A>G substitution was responsible for this aberrant splicing. This cryptic splice site has a Shapiro and Senapathy score (70.0) in a Normal Sequence but if mutated, the score (84.3) becomes higher than the one in the authentic splice donor site of intron 11 (81.4). This is an example in which a point mutation activates a cryptic splice donor site motif that is used preferentially over a downstream authentic splice site.
-
a novel single base substitution 380c t that activates a 5 base downstream cryptic splice acceptor site within exon 5 in almost all transcripts in the human mitochondrial acetoacetyl coa thiolase gene
Molecular Genetics and Metabolism, 2001Co-Authors: Kozue Nakamura, Toshiyuki Fukao, Celia Perezcerda, Cristobal Luque, Xiangqian Song, Yasuhiro Naiki, Yoshinori Kohno, Magdalena Ugarte, Naomi KondoAbstract:Abstract Most mutation-related aberrant splicing occurs in the conserved splice-acceptor and -donor sites and some exonic mutations also affect splicing. We identified and characterized a point mutation (380C>T) in a Spanish patient (GK25) with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. GK25 is a homozygote of 380C>T, which activates a cryptic splice-acceptor site 5 bases downstream from 380C>T within exon 5, causing aberrant splicing in 94% of transcripts. The aberrant splicing results in a 17-amino acids deletion, including the active-site 126Cys. The 380C>T mutation also results in A127V mutation in 6% of transcripts. Transient expression analysis showed that the A127V mutation did not retain T2 activity, indicating that 380C>T was a null mutation. Although this cryptic splice site has a higher Shapiro and Senapathy's score (86) in even a Normal Sequence than the authentic splice-acceptor site of intron 4 (78), it is not used in Normal controls. While the 380C>T mutation increases the score slightly (90), the cryptic splice site is used in almost all transcripts in GK25 fibroblasts. This is an example in which a point mutation activates a cryptic splice-acceptor site motif that is used preferentially over the upstream authentic splice site.
Jian Wang - One of the best experts on this subject based on the ideXlab platform.
-
homozygous missense mutation g56r in glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 gpi hbp1 in two siblings with fasting chylomicronemia mim 144650
Lipids in Health and Disease, 2007Co-Authors: Jian Wang, Robert A HegeleAbstract:Background Mice with a deleted Gpihbp1 gene encoding glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) develop severe chylomicronemia. We screened the coding regions of the human homologue – GPIHBP1 – from the genomic DNA of 160 unrelated adults with fasting chylomicronemia and plasma triglycerides >10 mmol/L, each of whom had Normal Sequence of the LPL and APOC2 genes.
Toshiyuki Fukao - One of the best experts on this subject based on the ideXlab platform.
-
a novel single base substitution c 1124a g that activates a 5 base upstream cryptic splice donor site within exon 11 in the human mitochondrial acetoacetyl coa thiolase gene
Molecular Genetics and Metabolism, 2008Co-Authors: Toshiyuki Fukao, Avihu Boneh, Yusuke Aoki, Naomi KondoAbstract:Abstract Most mutations related to aberrant splicing occur in conserved splice acceptor and donor sites. Some exonic mutations also affect splicing. We identified and characterized a point mutation (c.1124A>G) in an Australian patient (GK43) with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. GK43 is a homozygote of c.1124A>G, which activates a cryptic splice donor site 5 bases upstream from c.1124A>G within exon 11, causing aberrant splicing in most transcripts. The aberrant splicing results in c.1120–1163 (44-base) deletion, causing a frameshift in T2 mRNA. A mini-gene splicing experiment confirmed that the c.1124A>G substitution was responsible for this aberrant splicing. This cryptic splice site has a Shapiro and Senapathy score (70.0) in a Normal Sequence but if mutated, the score (84.3) becomes higher than the one in the authentic splice donor site of intron 11 (81.4). This is an example in which a point mutation activates a cryptic splice donor site motif that is used preferentially over a downstream authentic splice site.
-
a novel single base substitution 380c t that activates a 5 base downstream cryptic splice acceptor site within exon 5 in almost all transcripts in the human mitochondrial acetoacetyl coa thiolase gene
Molecular Genetics and Metabolism, 2001Co-Authors: Kozue Nakamura, Toshiyuki Fukao, Celia Perezcerda, Cristobal Luque, Xiangqian Song, Yasuhiro Naiki, Yoshinori Kohno, Magdalena Ugarte, Naomi KondoAbstract:Abstract Most mutation-related aberrant splicing occurs in the conserved splice-acceptor and -donor sites and some exonic mutations also affect splicing. We identified and characterized a point mutation (380C>T) in a Spanish patient (GK25) with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. GK25 is a homozygote of 380C>T, which activates a cryptic splice-acceptor site 5 bases downstream from 380C>T within exon 5, causing aberrant splicing in 94% of transcripts. The aberrant splicing results in a 17-amino acids deletion, including the active-site 126Cys. The 380C>T mutation also results in A127V mutation in 6% of transcripts. Transient expression analysis showed that the A127V mutation did not retain T2 activity, indicating that 380C>T was a null mutation. Although this cryptic splice site has a higher Shapiro and Senapathy's score (86) in even a Normal Sequence than the authentic splice-acceptor site of intron 4 (78), it is not used in Normal controls. While the 380C>T mutation increases the score slightly (90), the cryptic splice site is used in almost all transcripts in GK25 fibroblasts. This is an example in which a point mutation activates a cryptic splice-acceptor site motif that is used preferentially over the upstream authentic splice site.
Nicholas J Schork - One of the best experts on this subject based on the ideXlab platform.
-
rare variant phasing using paired tumor Normal Sequence data
BMC Bioinformatics, 2019Co-Authors: Alexandra R Buckley, Trey Ideker, Hannah Carter, Nicholas J SchorkAbstract:In standard high throughput sequencing analysis, genetic variants are not assigned to a homologous chromosome of origin. This process, called haplotype phasing, can reveal information important for understanding the relationship between genetic variants and biological phenotypes. For example, in genes that carry multiple heterozygous missense variants, phasing resolves whether one or both gene copies are altered. Here, we present a novel approach to phasing variants that takes advantage of unique properties of paired tumor:Normal sequencing data from cancer studies. VAF phasing uses changes in variant allele frequency (VAF) between tumor and Normal samples in regions of somatic chromosomal gain or loss to phase germline variants. We apply VAF phasing to 6180 samples from the Cancer Genome Atlas (TCGA) and demonstrate that our method is highly concordant with other standard phasing methods, and can phase an average of 33% more variants than other read-backed phasing methods. Using variant annotation tools designed to score gene haplotypes, we find a suggestive association between carrying multiple missense variants in a single copy of a cancer predisposition gene and earlier age of cancer diagnosis. VAF phasing exploits unique properties of tumor genomes to increase the number of germline variants that can be phased over standard read-backed methods in paired tumor:Normal samples. Our phase-informed association testing results call attention to the need to develop more tools for assessing the joint effect of multiple genetic variants.
