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G Bates

Publications and source records attributed to G Bates.

At least 37 records · Page 2Linked to original sources
PubMed1992

The Huntington's disease candidate region exhibits many different haplotypes.

Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180.

Alleles↗
PubMed1992

A novel G protein-coupled receptor kinase gene cloned from 4p16.3.

Within the Huntington's disease (HD) candidate region of 4p16.3, the D4S127 locus displays strong linkage disequilibrium with the defect and anchors a conserved haplotype found on many HD chromosomes. To isolate genes from this region we have applied the exon amplification technique to overlapping cosmids spanning D4S127. Here, we report the discovery of a new gene encoding a novel member of a family of protein kinases that specifically phosphorylate the activated forms of G protein-coupled receptors. Such kinases are thought to participate in desensitization of specific receptors, thereby blocking further signal transduction. This gene must now be carefully scrutinized to determine whether it might be involved in HD.

Amino Acid Sequence↗
PubMed1991

New DNA markers in the Huntington's disease gene candidate region.

The search for the Huntington's disease (HD) gene has prompted construction of a complete long-range restriction map of a 2.5-Mb candidate region, distal to the DNA marker D4S10. To facilitate the procurement of cloned DNA from this candidate region, we have augmented the existing regional mapping panel of somatic cell hybrids with hybrid HHW1071 containing a t(4p16;12) chromosome from a patient with Wolf-Hirschhorn syndrome. This translocation maps between D4S180 and D4S127, subdividing the HD candidate region and setting a proximal limit to the Wolf-Hirschhorn syndrome region. Using the expanded mapping panel, we have regionally assigned 14 independently cloned cosmids, five proximal to the t(4;12) breakpoint in the same region as D4S10 and nine distal to the breakpoint. By a combination of overlap with previously mapped cosmids and pulsed-field gel analysis, each of these cosmids has been positioned on the long-range restriction map of 4p16.3, increasing the clone coverage of the candidate region to approximately 40%. Single-copy probes from mapped cosmids were used to identify eight new DNA polymorphisms spanning the HD candidate region. These new DNA markers should prove valuable for analysis of recombination and linkage disequilibrium in HD, as well as for preclinical diagnosis of the disorder.

Alleles↗
PubMed1991

Complex patterns of linkage disequilibrium in the Huntington disease region.

The genetic defect causing Huntington disease (HD) has been mapped to 4p16.3 by linkage analysis using DNA markers. Two apparently contradictory classes of recombination events in HD kindreds preclude precise targeting of efforts to clone the disease gene. Here, we report a new recombination event that increases support for an internal candidate region of 2.5 Mb between D4S10 and D4S168. Analysis of 23 DNA polymorphisms in 4p16.3 revealed a complex pattern of association with the disease gene that failed to narrow the size of the candidate region. The degree of linkage disequilibrium did not show a continuous increase across the physical map, nor was a region of extreme disequilibrium identified. Markers displaying no association with the disorder were interspersed with and, in many cases, close to markers displaying significant disequilibrium. Comparison of closely spaced marker pairs on normal and HD chromosomes, as well as analysis of haplotypes across the HD region, suggest that simple recombination subsequent to a single original HD mutation cannot easily explain the pool of HD chromosomes seen today. A number of different mechanisms could contribute to the diversity of haplotypes observed on HD chromosomes, but it is likely that there has been more than one and possibly several independent origins of the HD mutation.

Alleles↗
PubMed1990

The human homeobox gene HOX7 maps to chromosome 4p16.1 and may be implicated in Wolf-Hirschhorn syndrome.

A cosmid containing the human sequence (HOX7) homologous to the mouse homeogene Hox-7 was isolated from a genomic cosmid library. There is only one highly conserved homologous gene in the human genome. The C-terminal two-thirds of the HOX7 homeobox DNA sequence has been determined; there are no predicted amino acid changes from the mouse sequence. Data from mouse/human hybrid cell lines show that HOX7 maps to human chromosome 4p16.1, a region that is syntenic with part of mouse chromosome 5, the site of the murine Hox-7 gene. Analysis of chromosomes from two patients with Wolf-Hirschhorn syndrome, which is characterised by profound dysmorphologies, indicates that the HOX7 locus is deleted. Although not all Wolf-Hirschhorn syndrome patients analysed were deleted for HOX7, the combination of positional data and functional correlation with mouse expression implicates HOX7 as a candidate gene for this syndrome.

Animals↗
PubMed1990

Analysis of the transgenome of MET transfectant cell lines reveals that MET activation is accompanied by an interstitial insertion.

The MET oncogene, present in the MNNG-HOS chemically transformed human cell line, is activated by a gene fusion involving sequences from chromosome 1 and chromosome 7. Activated MET can act as a dominant selectable marker for chromosome-mediated gene transfer, and several transfectant cell lines have been established using this technique. Analysis of the transgenomes within these cell lines indicates that MET activation is not simply due to a chromosome translocation, but may involve an interstitial insertion of DNA from chromosome 1, into chromosome 7, probably associated with other rearrangements. Pulse field gel analysis of two transfectants indicates that, despite the presence of complex rearrangements close to MET, chromosome 7 sequences are grossly intact over a 1-Mb region thought to contain the gene defective in cystic fibrosis.

Animals↗
PubMed1989

The role of bacterial infection of the maxillary sinus in nasal polyps.

Fifty-two adult patients with nasal polyps were studied. All patients had preoperative sinus radiographs which were coded on the degree of mucosal thickening and these were compared with the results of irrigation of the maxillary sinuses. All irrigations were sent for culture and microscopy for pus cells. Pus cells and bacteria were found in only 16 of 104 wash-outs. It was concluded that the disease results in stasis of secretions and secondary maxillary sinusitis.

Bacterial Infections↗
PubMed1988

A long-range restriction map encompassing the cystic fibrosis locus and its closely linked genetic markers.

The cystic fibrosis (CF) locus has been localized to the long arm of chromosome 7 by linkage analysis, and the genetic relationship between CF and the probes J3.11, met, and 7C22 has been extensively studied. To extend this genetic analysis to higher resolution, to provide information on physical distances underlying the genetic relationships, and to set limits to the position of the cystic fibrosis mutation, we have constructed a partial restriction map covering approximately 5 Mb that defines the physical relationship between these and the more recently isolated markers CS.7, XV-2c, Lcn2, and C2/5. Allelic association indicates that CS.7 and XV-2c are close to the CF locus, and an expressed sequence from this region has been described as a candidate gene for this mutation (X. Estivill et al., 1987, Nature (London) 326: 840-845). Using pulsed-field gel electrophoresis we have determined the physical order of these markers to be cen-7C22-Lcn2-met-C2/5-XV-2c-CS.7-J3.11-tel and have localized the CF mutation to an interval of less than 1500 kb. A (not unexpected) disproportionality was observed between the currently best estimates of genetic and physical distances, with the interval J3.11-met showing an approximately fourfold higher frequency of recombination than the met-7C22 interval.

Chromosome Mapping↗
PubMed1987

Biochemical and genetic exclusion of calmodulin as the site of the basic defect in cystic fibrosis.

Recent physiological studies have shown a defective beta-adrenergic regulation of chloride transport and protein secretion in tissues affected by cystic fibrosis. The exact biochemical nature of this abnormality is unknown, but an intracellular second messenger may be involved. We have tested the hypothesis that calmodulin is the site of the basic defect in CF using biochemical and molecular genetic techniques. We report here that there is no gross structural abnormality in the calmodulin protein from CF submandibular glands, and that although there are at least three distinct sequences that cross-hybridise with a calmodulin cDNA probe in the human genome, none of these can be the locus of CF. A polymorphism at the locus of a calmodulin cross-hybridising sequence at human chromosome 7p2 is described.

Alleles↗
PubMed1987

The application of molecular genetics to the study of the basic defect causing cystic fibrosis.

The first linkage to CF was demonstrated to the enzyme paroxonase, a classical protein polymorphism, by the Copenhagen group. This was followed quickly by six cloned DNA sequences: pJ3.11, 7C22, COL1A2 and TCRB (St. Mary's), 917 (Toronto) and met (Salt Lake City). Both pJ3.11 and met are very close genetically to the CF mutation, and can be used for carrier detection and antenatal diagnosis in many informative families where there is a CF child. There is no evidence for heterogeneity of the CF locus. The collection of markers surrounding the CF locus is now sufficient to permit attempts to be made to isolate the defective gene using a combination of chromosome-mediated gene transfer, pulse field gel electrophoresis, NotI junction libraries, cosmid mapping and chromosome walking techniques.

Chromosome Mapping↗
PubMed1986

Isolation of a further anonymous informative DNA sequence from chromosome seven closely linked to cystic fibrosis.

A library prepared from flow-sorted chromosomes was used to isolate single-copy sequences from chromosome seven. One such sequence 7C22 has been shown to be polymorphic for an EcoRI restriction site and to be informative for the study of CF in approximately 35% of matings. The segregation of the 7C22 alleles was followed through nineteen informative families with more than one child affected by cystic fibrosis. We report that the locus for 7C22 is linked to the locus for cystic fibrosis at a recombination fraction of 0.045. This marker will prove useful in improving the accuracy and informativeness of prenatal diagnosis and in constructing a fine genetic map around the cystic fibrosis gene.

Chromosomes, Human, 6-12 and X↗
PubMed1986

Further data supporting linkage between cystic fibrosis and the met oncogene and haplotype analysis with met and pJ3.11.

The linkage of cystic fibrosis (CF) and the polymorphic DNA markers pJ3.11, met, 7C22, DOCR1-917, COL1A2, and TCRB have jointly localized the mutation causing CF to chromosome 7q2.1-3.1. We report further linkage data with two polymorphic markers at the met oncogene locus, pmetH and pmetD, which supports the tight linkage found by White et al. between CF and met. One family shows evidence for meiotic recombination between CF and met. Analysis of haplotypes in CF pedigrees collected for linkage studies combined with data from single affected families requesting prenatal diagnosis (Farrall et al., Lancet i:1402-1404, 1986) shows CF and met to be in linkage equilibrium in our population while pJ3.11-CF haplotypes show a deviation from the equilibrium frequencies.

Cystic Fibrosis↗
PubMed1986

Ultrastructural alterations in glycosaminoglycans of dog femoral condylar cartilage after surgical division of an anterior cruciate ligament: a study with cupromeronic blue in a critical electrolyte concentration technique.

The cationic dye, cupromeronic blue, has been used in a critical electrolyte concentration technique to analyse the ultrastructural changes in cartilage matrix glycosaminoglycans which occur in the dog anterior cruciate ligament division model of osteoarthrosis. Amorphous material appearing at the articular surface of cartilage from the stifle joints of animals subjected to open surgical division of the anterior cruciate ligament has been shown not to comprise glycosaminoglycan. The nature of this material is unknown, but it appears to replace the surface lamina of normal cartilage. It may therefore affect the mechanical properties of the superficial cartilage. The pericellular matrix around single chondrocytes or separating pairs of chondrocytes becomes enriched with sulphated glycosaminoglycan as a response to ligament section. This material is thought to be newly synthesised and secreted and reflects the increased cellular activity resulting from surgically induced canine joint disease.

Animals↗
PubMed1985

Mapping DNA sequences in a human X-chromosome deletion which extends across the region of the Duchenne muscular dystrophy mutation.

A somatic cell hybrid has been constructed and characterized using fibroblasts from a phenotypically normal woman who possesses an X chromosome with an interstitial deletion of the short arm. High-resolution banding indicates that the deleted segment is either Xp22.13-p11.4 or Xp22.11-p11.23. Southern blot hybridization to previously mapped DNA sequences confirms that the missing segment of the X chromosome is a deletion and not an interstitial translocation and supports the cytogenetic interpretation that the deletion extends proximal of Xp11.3 and therefore probably comprises Xp22.11-p11.23. Three further DNA sequences have been localized to the region of the deleted segment. The following order has been assigned to the seven probes used: Xpter-RC8-pXUT22-(OA1,C7,M2C)-L1.28-RD6 -Xcen.

Animals↗