A5031272763- Developmental Biology and Gene Regulation
- Renal and related cancers
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Retinal Development and Disorders
- Connexins and lens biology
- Genomics and Chromatin Dynamics
- Ocular Disorders and Treatments
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Congenital heart defects research
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Congenital Ear and Nasal Anomalies
- Hedgehog Signaling Pathway Studies
- Immune Cell Function and Interaction
- interferon and immune responses
- Genomic variations and chromosomal abnormalities
- RNA Interference and Gene Delivery
- Reproductive Biology and Fertility
- dental development and anomalies
- T-cell and Retrovirus Studies
- Corneal Surgery and Treatments
- Epigenetics and DNA Methylation
- Cellular Mechanics and Interactions
- Intraocular Surgery and Lenses
University of Edinburgh
2002-2019
Institute of Genetics and Cancer
2000-2019
Western General Hospital
1998-2016
Hanson & Associates (United Kingdom)
2012
University College London
2004
Epilepsy Society
2004
Medical Research Council
1997
The Honourable Society of Lincoln's Inn
1989-1993
Oslo University Hospital
1993
University of Oslo
1993
We have identified a protein motif, related to the zinc finger, which defines newly discovered family of proteins. The motif was found in sequence human RING1 gene, is proximal major histocompatibility complex region on chromosome six. propose naming this "RING finger" and it 27 proteins, all putative DNA binding functions. synthesized peptide corresponding examined number properties, including metal binding. provide evidence support suggestion that RING finger domain defined
Current evidence suggests that aniridia (absence of iris) is caused by loss function one copy the PAX6 gene, which maps to 11p13. We present further characterisation two pedigrees in disease segregates with chromosomal rearrangements involve 11p13 but do not disrupt gene. have isolated three human YAC clones encompass locus and we used these show both cases breakpoint at least 85 kb distal 3' end PAX6. In addition, open reading frame apparently free mutations. propose gene on rearranged...
Abstract Background The PAX6 protein is a highly conserved transcriptional regulator that important for normal ocular and neural development. In humans, heterozygous mutations of the gene cause aniridia (absence iris) related developmental eye diseases. are archived in Human Allelic Variant Database, which currently contains 309 records, 286 patients with malformations. Results We examined records Database documented frequency different mutation types, phenotypes associated contribution CpG...
Aniridia is a congenital malformation of the eye, chiefly characterised by iris hypoplasia, which can cause blindness. The PAX6 gene was isolated as candidate aniridia positional cloning from smallest region overlap aniridia-associated deletions. Subsequently intragenic mutations were demonstrated in Smalleye, mouse mutant an animal model for aniridia, and six human patients. In this paper we describe four additional point patients, both sporadic familial. These highlight regions are...
Mutations of the human PAX6 gene underlie aniridia (congenital absence iris), a rare dominant malformation eye. The spectrum mutations in patients is highly biased, with 92% all reported leading to premature truncation protein (nonsense, splicing, insertions and deletions) just 2% substitution one amino acid by another (missense). extraordinary conservation at level amongst vertebrates predicts that pathological missense should fact be common even though they are hardly ever seen patients....
Identification of genes involved in human cerebral development is important for our understanding disorders with potential neurodevelopmental causes such as epilepsy and learning disability. Murine models suggest that PAX6 plays a key role brain development. With magnetic resonance imaging 24 humans heterozygous defined mutations, we demonstrated widespread structural abnormalities including absence the pineal gland unilateral polymicrogyria.
We report molecular genetic analysis of 42 affected individuals referred with a diagnosis aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 and 11 Gillespie syndrome (iris hypoplasia, ataxia mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing two FOXC1. Six deletions plausible cis-regulatory effects identified: five that 3ʹ (telomeric) one...
Most classical aniridia is caused by PAX6 haploinsufficiency. missense variants can be hypomorphic or mimic We hypothesized that also cause previously undescribed disease altering the affinity and/or specificity of genomic interactions. screened in 372 individuals with bilateral microphthalmia, anophthalmia, coloboma (MAC) from Medical Research Council Human Genetics Unit eye malformation cohort (HGUeye) and reviewed data Deciphering Developmental Disorders study. performed cluster analysis...
There is much interest in use of identity-by-descent (IBD) methods to map genes, both Mendelian and complex disorders. Homozygosity mapping provides a rapid means autosomal recessive genes consanguineous families by identifying chromosomal regions that show homozygous IBD segments pooled samples. In this report, we point out some potential pitfalls arose during the course homozygosity enhanced S-cone syndrome gene, resulting from (1) unexpected allelic heterogeneity, so region containing...
The RINC3 gene maps in the class II region of human major histocompatibility complex, at a CpC island distal HLA-DNA gene. R1NG3 cDNAs were obtained from T cell cDNA library and longest (4 kb) was sequenced. sequence contained an open reading frame encoding protein 754 amino acids. A screen databases revealed striking homology between RING3 Drosophila female sterile homeotic (fsh) which is implicated establishment segments early embryo. Partial also observed with some other proteins involved...