A5060828765- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Immunodeficiency and Autoimmune Disorders
- DNA Repair Mechanisms
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Hedgehog Signaling Pathway Studies
- Blood disorders and treatments
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Pediatric health and respiratory diseases
- Cell Adhesion Molecules Research
- Testicular diseases and treatments
- RNA Interference and Gene Delivery
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Cystic Fibrosis Research Advances
- Cancer Genomics and Diagnostics
- Acute Myeloid Leukemia Research
- Chromosomal and Genetic Variations
- RNA regulation and disease
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
University of Southampton
2015-2024
Faculty (United Kingdom)
2015
National Institutes of Health
2011
International Centre for Genetic Engineering and Biotechnology
2006-2010
University of Zurich
2009
Cold Spring Harbor Laboratory
2007
Karolinska Institutet
1994-2003
University College London
1995-2001
The Royal Free Hospital
1995-2001
University of Birmingham
2001
The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple carcinomas (BCCs), pits of the palms and soles, jaw keratocysts, a variety other tumors, developmental abnormalities. NBCCS maps to chromosome 9q22.3. Familial sporadic BCCs display loss heterozygosity in this region, consistent with gene being tumor suppressor. A human sequence (PTC) strong homology Drosophila segment polarity gene, patched, was isolated from YAC cosmid contig...
Mice that bear the X-linked immunodeficiency ( xid ) mutation have a B lymphocyte-specific defect resulting in an inability to make antibody responses polysaccharide antigens. A backcross of 1114 progeny revealed colocalization with Bruton's agammaglobulinemia tyrosine kinase btk gene, which is implicated human immune deficiency, agammaglobulinemia. carry missense alters highly conserved arginine near amino-terminus protein, Btk. Because this region Btk lies outside any obvious domain, may...
Drosophila patched is a segment polarity gene required for the correct patterning of larval segments and imaginal discs during fly development has close functional relationship with hedgehog. We have isolated complete human PATCHED cDNA sequence, which encodes putative protein 1296 amino acids, displays 39% identity 60% similarity to protein. Hydropathy analysis suggests that an integral membrane pattern hydrophobic hydrophilic stretches nearly identical patched. In developing mouse embryo,...
The frequency distribution of mutation-induced aberrant 3' splice sites (3'ss) in exons and introns is more complex than for 5' sites, largely owing to sequence constraints upstream intron/exon boundaries. As a result, prediction their localization remains challenging task. Here, nucleotide sequences previously reported 218 3'ss activated by disease-causing mutations 131 human genes were compared with authentic counterparts using currently available site tools. Each tested algorithm...
Despite a growing number of splicing mutations found in hereditary diseases, utilization aberrant splice sites and their effects on gene expression remain challenging to predict. We compiled sequences 346 5′splice (5′ss) that were activated by 166 human disease genes. Mutations within the 5′ss consensus accounted for 254 cryptic elsewhere 92 de novo 5′ss. Point leading activation most common first intron nucleotide, followed fifth nucleotide. Substitutions at position +5 exclusively G>A...
Missense, nonsense, and translationally silent mutations can inactivate genes by altering the inclusion of mutant exons in mRNA, but their overall frequency among disease-causing exonic substitutions is unknown. Here, we have tested missense deposited BRCA1 mutation databases unclassified variants for effects on exon inclusion. Analysis 21 using minigene assays revealed a single exon-skipping c.231G>T. Comprehensive mutagenesis an adjacent 12-nt segment showed that this resulted higher level...
Abstract To limit the region containing a mutation predisposing to selective IgA deficiency (IgAD) and common variable immunodeficiency (CVID), 554 informative members of 101 multiple-case families were haplotyped at IGAD1 candidate locus in MHC. Microsatellite markers placed onto physical map establish their order permit rapid haplotype analyses. Linkage analysis this extended family set provided additional support for strong susceptibility with maximum multipoint nonparametric linkage...
Abstract Selective IgA deficiency (IgAD) and common variable immunodeficiency (CVID) are the most primary immunodeficiencies in humans. A high degree of familial clustering, marked differences population prevalence among ethnic groups, association IgAD CVID families, a predominant inheritance pattern multiple-case pedigrees have suggested strong, shared genetic predisposition. Previous linkage, case-control, family-based studies mapped an IgAD/CVID susceptibility locus, designated IGAD1, to...
Abstract Mutations and diminished expression of the E‐cadherin gene (CDH1) have been identified in a number epithelial malignancies. Although somatic CDH1 mutations were detected lobular breast cancer with frequency ranging from 10–56%, alterations more frequent ductal tumors appear to be rare. Here we analyzed coding region for using denaturing high performance liquid chromatography found 4 83 carcinomas (5%) 3 25 (12%). The germline 13 patients familial was also mutations, but none...