A5028047183- Genetic factors in colorectal cancer
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Colorectal Cancer Treatments and Studies
- RNA Research and Splicing
- T-cell and B-cell Immunology
- Adenosine and Purinergic Signaling
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Cancer-related Molecular Pathways
- Genomic variations and chromosomal abnormalities
- Pluripotent Stem Cells Research
- Genomics and Rare Diseases
- Muscle Physiology and Disorders
- Migraine and Headache Studies
- BRCA gene mutations in cancer
- Blood groups and transfusion
- Peptidase Inhibition and Analysis
- Soft tissue tumor case studies
- Epigenetics and DNA Methylation
- Digestive system and related health
Leiden University Medical Center
2013-2024
Leiden University
1990-2020
Netherlands Bioinformatics Centre
2014
Center for Human Genetics
2003
Huntsman Cancer Institute
1999
University of Utah
1999
Utrecht University
1998-1999
Albert Einstein College of Medicine
1999
Yeshiva University
1999
Institute of Human Genetics
1989-1998
Germ-line mutations in the human adenomatous polyposis coli (APC) gene result familial polyposis, an autosomal dominant disorder characterized by early onset of multiple polyps large bowel with a high likelihood developing colorectal carcinomas. To understand role APC intestinal tumor formation, we have introduced chain-termination mutation 15th exon mouse Apc and employed it to modify endogenous homologous recombination embryonic stem cells. Mice which are heterozygous for modification...
According to the classical interpretation of Knudson's 'two-hit' hypothesis for tumorigenesis, two 'hits' are independent mutation events, end result which is loss a tumor suppressing function. Recently, it has been shown that APC (adenomatous polyposis coli) gene does not entirely follow this model. Both position and type second hit in familial adenomatous (FAP) polyps depend on localization germline mutation. This non-random distribution somatic hits interpreted as selection more...
Ron Smits, Menno F. Kielman, Cor Breukel, Chris Zurcher, Kristi Neufeld, Shantie Jagmohan-Changur, Nandy Hofland, Jaap van Dijk, Ray White, Winfried Edelmann, Raju Kucherlapati, P. Meera Khan, and Riccardo Fodde Medical Genetics Center (MGC) Department of Human Genetics, Leiden University Center, 2300 RA Leiden, The Netherlands; Veterinary Pathology, Utrecht, Huntsman Cancer Institute, Utah, Salt Lake City, Utah 84112 USA; Departments Cell Biology Molecular Albert Einstein College Medicine...
Disruption of cell division cycle associated 7 (CDCA7) has been linked to aberrant DNA hypomethylation, but the impact methylation loss on transcription not investigated. Here, we show that CDCA7 is critical for maintaining global levels across multiple tissues in vivo. A pathogenic
FcγRIIB-deficient mice generated in 129 background (FcγRIIB(129)(-/-)) if back-crossed into C57BL/6 exhibit a hyperactive phenotype and develop lethal lupus. Both humans, the Fcγr2b gene is located within genomic interval on chromosome 1 associated with lupus susceptibility. In mice, 129-derived haplotype of this interval, named Sle16, causes loss self-tolerance context B6 genome, hampering analysis specific contribution FcγRIIB deficiency to development FcγRIIB(129)(-/-) mice. Moreover,...
Abstract Here we show, for the first time, spontaneous cortical spreading depolarization (CSD) events – electrophysiological correlate of migraine aura in animals by using generated familial hemiplegic type 3 (FHM3) transgenic mouse model. The mutant mice express L263V‐mutated α 1 subunits voltage‐gated Na V 1.1 sodium channels ( Scn1a L263V ). CSDs consistently propagated from visual to motor cortex, recapitulating what has been shown patients with aura. This model may be valuable...
Germline mutations in the adenomatous polyposis coli (APC) gene are responsible for familial (FAP), an autosomal dominant hereditary predisposition to development of multiple colorectal adenomas and a broad spectrum extra-intestinal tumors. Moreover, somatic APC play rate-limiting initiating role majority sporadic cancers. Notwithstanding its multifunctional nature, main tumor suppressing activity resides ability regulate Wnt/β-catenin signaling. Notably, genotype–phenotype correlations have...
Mutations of the adenomatous polyposis coli ( APC ) gene predispose individuals to familial (FAP), characterized by multiple tumours in large intestine. Most mouse models heterozygous for truncating mutant Apc alleles mimic FAP, however, intestinal occur mainly small To model tumours, we generated a new conditional -mutant allele, Apc15lox , with exon 15 flanked loxP sites. Similar survival Apc1638N/15lox and Apc1638N/+ mice indicated that normal function was not impaired Deletion 15,...
Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease generally caused by reading frame disrupting mutations in the DMD gene resulting loss of functional dystrophin protein. The can be restored antisense oligonucleotide (AON)-mediated exon skipping, allowing production internally deleted, but partially proteins as found less Becker dystrophy. Due to genetic variation between species, mouse models with murine genes are limited use test and further optimize human specific AONs...
Cell fate decisions are orchestrated by an interplay of epigenetic factors in collaboration with transcriptional activators and repressors. The reader MORC3 is known as a silencer endogenous retroviruses mouse embryonic stem cells. Here, we show that expressed the thymus reveal loss function leads to severe arrest T cell development at DN1 stage, accompanied expansion natural killer myeloid depends on its ATPase ability bind H3K4me via CW-type zinc finger domain. We find altered chromatin...
The APC gene, originally identified as the gene for familial adenomatous polyposis (FAP), is now considered true “gatekeeper” of colonic epithelial proliferation. Its main tumor suppressing activity seems to reside in capacity properly regulate intracellular β-catenin signaling. Most somatic mutations are detected between codons 1286 and 1513, mutation cluster region (MCR). This clustering can be explained either by presence mutation-prone sequences within MCR, or selective advantage...
Abstract Motivation: Advances in sequencing technologies and computational algorithms have enabled the study of genomic variants to dissect their functional consequence. Despite this unprecedented progress, current tools fail reliably detect characterize more complex allelic variants, such as short tandem repeats (STRs). We developed TSSV an efficient sensitive tool specifically profile all present targeted loci. Based on its design, requiring only two flanking sequences, can work without...
Abstract Genomic deletions of the MSH2 gene are a frequent cause hereditary nonpolyposis colorectal cancer (HNPCC), common predisposition to development tumors in several organs including gastrointestinal and urinary tracts endometrium. The mutation spectrum at is extremely heterogeneous because it includes nonsense missense point mutations, small insertions leading frameshifts, larger genomic deletions, latter representing approximately 25% total burden. Here, we report identification...
The polymorphic CA repeat CAMBC was isolated and characterized from cosmid cLDMBC.Cosmid cLDMBC derived by screening the flow sorted chromosome 5 library LAO5NCO1 with MCC cDNA probe SW15