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Biomedical subjects

B Sykes

Publications and source records attributed to B Sykes.

At least 73 records · Page 4Linked to original sources
PubMed1990

Amplification of the COL2A1 3' variable region used for segregation analysis in a family with the Stickler syndrome.

Amplification of a variable region 3' to the human type II collagen gene (COL2A1) has permitted segregation analysis in a three generation Stickler syndrome pedigree. This family had previously proved uninformative for the known restriction fragment length dimorphisms. Amplification of the variable region revealed five distinguishable alleles, of which three were segregating in this family. The lod score in favour of linkage was 2.86 at zero recombination.

Abnormalities, Multiple↗
PubMed1990

Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2.

The segregation of COL1A1 and COL1A2, the two genes which encode the chains of type I collagen, was analyzed in 38 dominant osteogenesis imperfecta (OI) pedigrees by using polymorphic markers within or close to the genes. This was done in order to estimate the consistency of linkage of OI genes to these two loci. None of the 38 pedigrees showed evidence of recombination between the OI gene and both collagen loci, suggesting that the frequency of unlinked loci in the population must be low. From these results, approximate 95% confidence limits for the proportion of families linked to the type I collagen genes can be set between .91 and 1.00. This is high enough to base prenatal diagnosis of dominantly inherited OI on linkage to these genes even in families which are too small for the linkage to be independently confirmed to high levels of significance. When phenotypic features were compared with the concordant collagen locus, all eight pedigrees with Sillence OI type IV segregated with COL1A2. On the other hand, Sillence OI type I segregated with both COL1A1 (17 pedigrees) and COL1A2 (7 pedigrees). The concordant locus was uncertain in the remaining six OI type I pedigrees. Of several other features, the presence or absence of presenile hearing loss was the best predictor of the mutant locus in OI type I families, with 13 of the 17 COL1A1 segregants and none of the 7 COL1A2 segregants showing this feature.

Chromosomes, Human, Pair 17↗
PubMed1990

Basal metabolic rate in monozygotic and dizygotic twins.

The basal metabolic rate (BMR) was determined in 14 pairs of monozygotic (MZ; 11 females, 3 males) and 12 pairs of dizygotic (DZ; 10 females, 2 males) twins, with mean ages of 22.7 and 26 years. Zygosity was confirmed using DNA fingerprinting. When BMR was expressed as kJ/d, kJ/kg/d and kJ/kg FFM/d significant intra-class correlation coefficients were observed in the MZ twins of 0.82, 0.79 and 0.85, respectively. The DZ twins showed much lower intra-class correlations coefficients of 0.1, 0.07 and -0.04. Although the results of the study suggest a likely genetic component to the variation in BMR, they should be interpreted with caution as heritability estimates vary with the method of calculation. These will be critically discussed in the paper.

Adult↗
PubMed1989

Genetic segregation analysis of familial mitral valve prolapse shows no linkage to fibrillar collagen genes.

Three pedigrees were identified in which mitral valve prolapse seemed to be inherited as a mendelian autosomal dominant trait. The segregation of the genes encoding the major fibrillar collagens present in valve tissue, collagens I and III, was analysed by use of restriction enzyme site variants as genetic markers. In one pedigree there was discordance between the segregation of the disease and markers for all three collagen genes. In another, there was discordance between the disease and markers for both collagen I loci. This is evidence against the disease being generally the result of mutations of the genes encoding the major fibrillar collagens.

Collagen↗
PubMed1989

Inherited collagen disorders.

The investigation of the inherited matrix disorders has been an example of progress on two parallel fronts. Two decades of protein chemistry have provided detailed background information on the structure, if not the function, of collagen. This has been used to identify the likely candidate genes for analysis using DNA markers. Segregation analysis has in turn sorted out which diseases are caused by collagen gene mutations and which are not. This information is now concentrating effort on defining the mutations in the linked diseases and establishing linkages to other genes in the rest. Using the background structural information, efficient and specific strategies for rapidly identifying individual mutants are being designed. Best of all, prenatal diagnosis is now a reality for many parents faced with the prospect of having a severely crippled child.

Collagen↗
PubMed1988

Interferon-inhibited human osteosarcoma xenografts induce host bone in nude mice.

The growth of human osteosarcoma xenografts in nude mice can be inhibited by human interferon-alpha (IFN-alpha). Histologic examination of growth-inhibited tumors has revealed mineralization and partial replacement of the tumor by normal bone tissue. We have investigated whether the normal bone tissue was formed by differentiated tumor cells or by induction of host stroma to differentiate into bone tissue. Employing antibodies to both murine and human type I collagen, it was found that the normal bone produced in IFN-inhibited osteosarcomas was host derived. These results suggest that IFN induced the osteosarcoma cells to produce a bone-inductive agent that interacts with the host cells, and leads to the formation of mature normal bone tissue in a heterotopic site.

Animals↗
PubMed1988

Homozygous osteogenesis imperfecta unlinked to collagen I genes.

In a consanguineous pedigree in which a severe type of osteogenesis imperfecta was segregating as an autosomal recessive trait, analysis of genetic markers for both collagen I structural loci COL1A1 and COL1A2 showed that the phenotype was unlinked to either locus.

Collagen↗
PubMed1988

Structural and segregation analysis of the type II collagen gene (COL2A1) in some heritable chondrodysplasias.

Seventy-seven persons with a variety of heritable chondrodysplasias were screened for gross rearrangements of the structural gene encoding the major cartilage collagen, collagen II. None was found. Segregation of the locus (COL2A1) was studied in 19 pedigrees using three restriction site dimorphisms (shown by PvuII, HindIII, and BamHI) and a length polymorphism as linkage markers. Discordant segregation between COL2A1 and the mutant locus was seen in pedigrees with multiple epiphyseal dysplasia, autosomal recessive spondyloepiphyseal dysplasia tarda, hypochondroplasia, pseudoachondroplasia, diaphyseal aclasis, and trichorhinophalangeal syndrome. One pedigree with diastrophic dysplasia was weakly concordant. Autosomal dominant spondyloepiphyseal dysplasia tarda and metaphyseal chondrodysplasia (type Schmid) were not informative. We conclude that mutations of the collagen II gene are not a common feature of the heritable chondrodysplasias. Since the chondrocyte binding protein, chondrocalcin, is also encoded at COL2A1 our conclusions apply equally to this gene.

Calcium-Binding Proteins↗
PubMed1987

Joint mobility with particular reference to racial variation and inherited connective tissue disorders.

Joint mobility scores were compared in 248 normal English Caucasian males and females between the ages of 8 and 70 years. The results were contrasted with those in a group of normal Asian Indians and patients suffering from a variety of inherited disorders including Type II Ehlers-Danlos syndrome (EDS), Type I osteogenesis imperfecta (OI), Marfan syndrome, generalized osteoarthritis (GOA), achondroplasia and pseudoachondroplasia. The first-degree relatives of ten subjects with severe or lethal OI were also examined. Asian Indians were significantly more mobile than English Caucasians. Males and females with EDS were hypermobile but only the females with OI and the female relatives of those with severe or lethal OI showed excess joint laxity. Patients with pseudoachondroplasia exhibited a grosser type of joint laxity than other subjects while those with GOA represented a relatively stiff group. No evidence was found to support the view that hypermobility is associated with particular length variants at the Type II collagen structural gene locus (COL2A1).

Achondroplasia↗
PubMed1986

Osteogenesis imperfecta is linked to both type I collagen structural genes.

The segregation of the two type I collagen structural gene loci COL1A1 and COL1A2 was analysed in eleven osteogenesis imperfecta pedigrees by means of restriction-site variants at, or close to, these loci. In each case, the OI gene was inherited with one or other collagen locus. As well as identifying the common OI loci the result of this analysis sets limits on the frequency of a third locus and lays the foundation for a widely available antenatal diagnostic test.

Chromosome Mapping↗
PubMed1986

Evidence against the structural gene encoding type II collagen (COL2A1) as the mutant locus in achondroplasia.

The structure of the locus encoding the major cartilage collagen gene (COL2A1) was studied in a total of 19 cases of achondroplasia. No gross rearrangements were seen. The segregation of COL2A1 was examined in three affected kindreds using restriction site and length variants as genetic markers. In two kindreds discordant segregation between the achondroplasia and COL2A1 loci was demonstrated. Paternity/maternity was confirmed using a 'minisatellite' core sequence probe which reveals cross hybridising polymorphic loci.

Achondroplasia↗