Biomedical subjects

M Dawn Teare

Publications and source records attributed to M Dawn Teare.

6 recordsLinked to original sources

PubMed2005

Meta-analysis of five genome-wide linkage studies for body mass index reveals significant evidence for linkage to chromosome 8p.

OBJECTIVE: To perform a meta-analysis of genome-wide linkage scans using body mass index (BMI) to identify genetic loci predisposing to obesity. DATA: A total of 13 published genome scans on obesity have used BMI as their primary end point. Five of these 13 groups agreed to provide detailed results from their scans that were required for a meta-analysis. Collectively, these five studies included a total of 2814 individuals from 505 families. METHODS: The results of the five studies were analysed using the GSMA (genome scans meta-analysis) method. RESULTS: The analysis revealed significant evidence for linkage of the quantitative phenotype BMI to 8p (P<0.0005).

Adult↗

PubMed2004

Association of a common variant of the CASP8 gene with reduced risk of breast cancer.

Apoptosis, or programmed cell death, is perturbed in many cancers. We tested the hypothesis that coding polymorphisms of the death receptor 4 (DR4), caspase-8 (CASP8), and caspase-10 (CASP10) genes might act as low-penetrance breast cancer genes. Single-nucleotide polymorphisms (SNPs) of these genes were genotyped in a series of 999 breast cancer case patients and 996 control subjects from Sheffield, U.K., and in a second, independent U.K. population of 2192 case patients and 2262 control subjects from East Anglia. In the Sheffield study, the rare H allele of CASP8, D302H, was associated with a reduced risk of breast cancer in a dose-dependent manner (P(trend) = .007). Furthermore, the CASP8 D302H association, but not that of the other CASP8 SNPs examined (T21914C, G50121A, and G50358A), was replicated in the East Anglian study. The combined adjusted odds ratios for breast cancer were 0.83 (95% confidence interval [CI] = 0.74 to 0.94) for the DH heterozygote and 0.58 (95% CI = 0.39 to 0.88) for the HH homozygote (P(trend) = .0002, adjusted for study). The reproducible, dose-dependent association of CASP8 D302H with breast cancer indicates the potential importance of inherited variation in the apoptosis pathway in breast cancer susceptibility.

Aspartic Acid↗

PubMed2003

Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis.

Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are autosomal recessive conditions characterized by multiple subcutaneous skin nodules, gingival hypertrophy, joint contractures, and hyaline deposition. We previously mapped the gene for JHF to chromosome 4q21. We now report the identification of 15 different mutations in the gene encoding capillary morphogenesis protein 2 (CMG2) in 17 families with JHF or ISH. CMG2 is a transmembrane protein that is induced during capillary morphogenesis and that binds laminin and collagen IV via a von Willebrand factor type A (vWA) domain. Of interest, CMG2 also functions as a cellular receptor for anthrax toxin. Preliminary genotype-phenotype analyses suggest that abrogation of binding by the vWA domain results in severe disease typical of ISH, whereas in-frame mutations affecting a novel, highly conserved cytoplasmic domain result in a milder phenotype. These data (1) demonstrate that JHF and ISH are allelic conditions and (2) implicate perturbation of basement-membrane matrix assembly as the cause of the characteristic perivascular hyaline deposition seen in these conditions.

Amino Acid Sequence↗

PubMed2003

Ehlers-Danlos syndrome with severe early-onset periodontal disease (EDS-VIII) is a distinct, heterogeneous disorder with one predisposition gene at chromosome 12p13.

Ehlers-Danlos VIII (EDS-VIII) is an autosomal dominant disorder characterized by severe early-onset periodontal disease in conjunction with the features of Ehlers-Danlos syndrome (EDS). We performed a genomewide linkage search in a large Swedish pedigree with EDS-VIII and established linkage to a 7-cM interval on chromosome 12p13, generating a maximum multipoint LOD score of 5.17. Analysis of four further pedigrees with EDS-VIII revealed two consistent with linkage to 12p13 and two in which linkage could be excluded, indicating that EDS-VIII is a genetically heterogeneous disorder. Chromosome 12p13 has not previously been implicated in either EDS or periodontal disease and contains no known collagen genes or collagen-processing enzymes. Mutational screening of the microfibril-associated glycoprotein-2 gene, a strong candidate within the minimal interval, did not reveal any likely pathogenic mutations.

Age of Onset↗

PubMed2002

The gene for juvenile hyaline fibromatosis maps to chromosome 4q21.

Juvenile hyaline fibromatosis (JHF) is an autosomal recessive condition characterized by multiple subcutaneous nodular tumors, gingival fibromatosis, flexion contractures of the joints, and an accumulation of hyaline in the dermis. We performed a genomewide linkage search in two families with JHF from the same region of the Indian state of Gujarat and identified a region of homozygosity on chromosome 4q21. Dense microsatellite analyses within this interval in five families with JHF who were from diverse origins demonstrate that all are compatible with linkage to chromosome 4q21 (multipoint LOD score 5.5). Meiotic recombinants place the gene for JHF within a 7-cM interval bounded by D4S2393 and D4S395.

Child↗

PubMedDate not supplied

Genetic linkage studies.

Linkage analysis is used to map genetic loci by use of observations of related individuals. We provide an introduction to methods commonly used to map loci that predispose to disease. Linkage analysis methods can be applied to both major gene disorders (parametric linkage) and complex diseases (model-free or non-parametric linkage). Evidence for linkage is most commonly expressed as a logarithm of the odds score. We provide a framework for interpretation of these scores and discuss the role of simulation in assessment of statistical significance and estimation of power. Genetic and phenotypic heterogeneity can also affect the success of a study, and several methods exist to address such problems.

Chromosome Mapping↗