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Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P
- Source :
- Human Genetics. 112:209-216
- Publication Year :
- 2003
- Publisher :
- Springer Science and Business Media LLC, 2003.
-
Abstract
- Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant inflammatory disease with a high degree of penetrance that is characterized by episodes of rash, arthralgia, fever, conjunctivitis, and leukocytosis after generalized exposure to cold. FCAS was previously mapped to a 10-cM region on chromosome 1q44, and subsequently the gene ( CIAS1) responsible for FCAS was identified. In this paper, we describe the physical and genetic mapping of the FCAS locus, and we report a large ancestral haplotype and a new disease-causing mutation. A BAC contig of approximately 3 Mb was developed and subsequently used for high throughput sequencing. We identified a critical region of 4 cM using rare crossover events in four large North American FCAS families. An unusually large shared haplotype (40 cM) was identified in three of the four families. We found a single heterozygous missense mutation (T1058C=L353P) in exon 3 of CIAS1 in all four families that is responsible for the large majority of FCAS cases described in the literature. We also report a comprehensive list of intragenic single nucleotide polymorphisms. The data provided here will assist others researching the 1q44 region and will aid clinicians in the diagnosis of FCAS.
- Subjects :
- Male
Chromosomes, Artificial, Bacterial
Genetic Linkage
DNA Mutational Analysis
Mutation, Missense
Single-nucleotide polymorphism
Locus (genetics)
Biology
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Autoimmune Diseases
Gene mapping
Familial Cold Autoinflammatory Syndrome
NLR Family, Pyrin Domain-Containing 3 Protein
Genetics
Humans
Missense mutation
Genetics (clinical)
DNA Primers
Contig
Haplotype
Chromosome Mapping
Blood Proteins
Physical Chromosome Mapping
Penetrance
Familial Mediterranean Fever
Pedigree
Cold Temperature
Haplotypes
Female
Lod Score
Carrier Proteins
Microsatellite Repeats
Subjects
Details
- ISSN :
- 14321203 and 03406717
- Volume :
- 112
- Database :
- OpenAIRE
- Journal :
- Human Genetics
- Accession number :
- edsair.doi.dedup.....78e02ed014793e19a1b84fdb3e5b2b73