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R S Sparkes

Publications and source records attributed to R S Sparkes.

At least 181 records · Page 10Linked to original sources
PubMed1985

Genetic linkage studies in ataxia-telangiectasia: Gm markers.

Gm marker studies were performed on seven families with ataxia-telangiectasia in order to determine genetic linkage. For statistical analysis, the disorder was assumed to be monogenic. Using LOD scores computed by the program LIPED, tight linkage was excluded at a recombination fraction of less than or equal to 2 cM. This distance (equivalent to approximately two million nucleotides) includes most or all of the 14q32 chromosomal region.

Ataxia Telangiectasia↗
PubMed1985

Neoplasia and chromosomal breakage in ataxia-telangiectasia: a 2:14 translocation.

Four common sites of chromosome breakage have been observed in patients with ataxia-telangiectasia (AT): 7p14, 7q35, 14q11.2, and 14q32. These sites appear to coincide with the location of genes for the T-cell receptor subunits (alpha, beta, and gamma) and IGH. Each of these genes involves rearrangements of DNA for its expression, suggesting that an abnormal DNA processing enzyme or family of enzymes underlies this propensity for chromosomal breakage in AT patients. Such a defect could also explain the radiation hypersensitivity of AT fibroblasts. In view of these findings, it is perhaps surprising that AT patients do not manifest more severe immunological defects although they would explain the lack of uniformity of these defects from one patient to the next. Two other genes utilize DNA rearrangement, IGK (on chromosome 2p12) and IGL (on chromosome 22q11), and have not been noted previously to be involved in translocations in these patients. We report here a 2:14 translocation (p14:q32) in a phytohemagglutinin-stimulated lymphocyte from a patient with AT.

Adult↗
PubMed1984

Anti-apoprotein B monoclonal antibodies detect human low density lipoprotein polymorphism.

Immunochemical polymorphism among human low density lipoproteins (LDL) isolated from different individuals was demonstrated through reduced binding of three monoclonal antibodies to some individual LDL using a solid phase radioimmunoassay. These three antibodies are members of a larger group of monoclonal antibodies previously shown to bind specifically to apoprotein B ( Curtiss , L.K., and Edgington , T. S. (1982) J. Biol. Chem. 257, 15213-15221; Tsao , B.P., Curtiss , L. K., and Edgington , T.S. (1982) J. Biol. Chem. 257, 15222-15228). Those antibodies which distinguished human LDL polymorphism bound to the same or adjacent epitopes on LDL, for they were mutually exclusive in competitive binding experiments. Binding was unaffected by treatment with neuraminidase, with a mixture of glycosidases, or with competing glycoproteins; thus, the carbohydrate moiety of apoprotein B did not appear to influence the epitope recognized by these antibodies. When low density lipoproteins isolated from different individuals were studied, three different phenotypes were recognized; these corresponded to strong, weak, and intermediate binding of the three monoclonal antibodies. This division into three phenotypes is demonstrated to result from a genetic polymorphism; indeed, the data fit a model consisting of two co-dominant apoprotein B alleles, and the three phenotypes then correspond to the two human homozygotes and the heterozygote. The classical Ag antigen phenotype was determined for the LDL isolated from 10 individuals who were also studied with the monoclonal antibodies, and no correspondence was found between the different epitopes recognized by the five presumptive Ag allelic pairs, x/y, a1/d, c/g, t/z, or h/i, and the site recognized by the monoclonal antibodies. All of these data are discussed, and it is concluded that the most likely explanation for the difference in recognition of the two allelic forms of apoprotein B is an alteration in amino acid sequence resulting in a slightly different configuration of a single domain containing the epitopes recognized by the three monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1984

Estimating the recombination frequency for the PTC-Kell linkage.

Two data sets are analyzed for linkage between the PTC and Kell blood group loci. The original report of close linkage for these loci was that of Conneally et al. (1976), where the maximum likelihood estimate of theta was 0.05. These two new data sets give a combined maximum likelihood estimate of theta m = f = 0.28. Estimating the recombination frequency for the sexes separately gave theta m = 0.29, theta f = 0.23. The combined maximum likelihood estimate over all published data sets including this report is theta m = f = 0.14, Zmax = 8.94. There is statistically significant evidence of heterogeneity among the published studies.

Blood Group Antigens↗
PubMed1984

Transferase-deficiency galactosemia: immunochemical studies of the Duarte and Los Angeles variants.

Rabbit antibodies to purified human placental galactose-1-phosphate uridyltransferase (EC 2.7.7.12) were used to establish immunologic cross-reactivity patterns for the enzyme in hemolysates, prepared from red cells of a normal individual, a homozygous Duarte variant, and a heterozygous Los Angeles variant. The antibody immunoprecipitated all three forms of the enzyme. The amount of antibody absorbed by each hemolysate was related to the different levels of activity, and examination of hemolysate/antibody reaction mixtures by starch gel electrophoresis revealed that the antibody quantitatively precipitated all of the isoenzyme forms that characterize these three genetic variants.

Animals↗
PubMed1984

Regional localization of the human genes for S-adenosylhomocysteine hydrolase (cen----q131) and adenosine deaminase (q131----qter) on chromosome 20.

The gene loci for S-adenosylhomocysteine hydrolase ( AHCY ) and adenosine deaminase (ADA), two enzymes with related metabolic functions, have both been assigned to human chromosome 20. We have used rodent-human somatic hybrids containing translocations involving human chromosome 20 to more precisely determine the relative locations of the AHCY and ADA loci. Our results assign the AHCY locus to the long arm of chromosome 20, in the region cen---- q131 , and ADA to the region q131 ----qter.

Adenosylhomocysteinase↗
PubMed1984

Wilms' tumor-aniridia association: segregation of affected chromosome in somatic cell hybrids, identification of cell surface antigen associated with deleted area, and regional mapping of c-Ha-ras-1 oncogene, insulin gene, and beta-globin gene.

Fusion of an auxotrophic mutant hamster cell with the skin fibroblasts of a child with the Wilms' tumor-aniridia association produced clones which, on the one hand, contained the child's normal chromosome 11 and, on the other, the chromosome 11 with the 11p13 deletion associated with the syndrome. Both hybrids were positive for human LDH-A by enzymatic assay. Clones containing the normal human chromosome 11 were killed by a cytotoxic monoclonal antibody to a cell surface antigen previously mapped to the 11p13----11pter region of chromosome 11. Clones with the abnormal 11 were not killed. Thus, we have produced hybrids from the same patient distinct from each other on the basis of their chromosome 11. These hybrids have been used to map the locus for a cell surface antigen to the deleted region on chromosome 11 of a patient with the Wilms tumor-aniridia association. The linkage between this antigen and the syndrome should be helpful in further study of the genetics of this disease. In addition, we have found that the c-Ha-ras-1 oncogene is distal to the p13 region of chromosome 11 and the position of insulin and beta-globin on the chromosome. Finally, by producing segregants of the hybrids containing the abnormal chromosome 11, we have provided evidence that chromosome 11-associated c-Ha-ras-1 is syntenic with chromosome 11 and not moved to a different portion of the genome.

Animals↗
PubMed1984

Peters' anomaly associated with partial deletion of the long arm of chromosome 11.

A 5-week-old boy with Peters' anomaly was found to have an interstitial deletion of the long arm of chromosome 11; no developmental delays or dysmorphic features were evident. His right cornea was enlarged and opaque with extensive pannus formation; the anterior chamber, iris, and lens were not visible. The left eye showed a central opacity and a superficial pannus; the optic disk and macula could not be visualized. He underwent bilateral corneal transplantation. Histologic examination of the corneal buttons confirmed the diagnosis. The potential genetic mechanisms in this case included a gene for this autosomal recessive disorder on the long arm of chromosome 11, generalized disruption of the embryogenesis of the anterior segment as a result of the deleted material, or simple autosomal recessive inheritance unrelated to the chromosomal deletion.

Chromosome Aberrations↗
PubMed1984

Bone marrow transplantation from identical twins in the treatment of aplastic anaemia: implication for the pathogenesis of the disease.

Treatment of aplastic anaemia by bone marrow transplantation from a syngeneic (identical twin) donor has provided insights into the pathophysiology of the disease. We report from patients with severe anaemia who were treated by syngeneic bone marrow transplantation. None of the patients had sustained recovery of peripheral blood counts. All four received second transplants from the same twin donor after immunosuppressive conditioning treatment. Each had prompt recovery of haematopoiesis. A review of the literature indicates that failure of syngeneic bone marrow transplantation in patients with aplastic anaemia is not uncommon. These data indicate that aplastic anaemia may be caused by a mechanism other than an absence or intrinsic abnormality of haematopoietic stem cells in many patients.

Adolescent↗
PubMed1984

Evidence of autonomous red cell expression of Xga antigen in human bone marrow transplantation.

Human bone marrow transplant chimeras afford the opportunity to determine whether a red blood cell antigen is autonomously controlled. Evaluation of an Xg(a-) recipient and an Xg(a+) recipient, each transplanted with bone marrow of donors of opposite Xga types, shows that the Xga antigen is of the donor type following transplantation. This indicates that the Xga antigen is controlled by the red blood cell, and confirms earlier studies in natural chimeras.

Adolescent↗
PubMed1984

Trisomy 18 phenotype in a patient with an isopseudodicentric 18 chromosome.

We report a female patient with a typical trisomy 18 phenotype who has a 46,XX, -18, +isopseudodic(18)(p11) karotype. The lack of features of the 18p- syndrome suggests that a significant amount of short arm material is present and that the Turner-like features associated with 18p- may be determined by monosomy for 18p11. The phenotype-genotype correlations in abnormalities affecting chromosome 18 are reviewed.

Chromosome Aberrations↗
PubMed1984

Genetic linkage studies of transferrin, pseudocholinesterase, and chromosome 1 loci.

Genetic linkage analysis of a pedigree with four different alleles for pseudocholinesterase (CHE1) gives a positive lod score of 0.37 at theta = 0.16 for linkage with transferrin (TF), a finding which supports previous reports of linkage between CHE1 and TF. Evaluation of linkage relations of CHE1 and TF using unreported families from our data bank fails to establish linkage with chromosome 1 loci (6-PGD, Rh, PGM1, AMY2 and FY). These results are consistent with recent studies which suggest that TF is on human chromosome 3.

Alleles↗
PubMed1984

Chromosome deletion mapping of interspersed low-copy repetitive DNA.

A cloned 2.2 Eco RI segment of interspersed repetitive DNA was hybridized to genomic DNA from a mentally retarded patient with an interstitial deletion in the long arm of one chromosome 12 (12q-). Under hybridization conditions of high stringency, one prominent 2.2-kilobase (kb) Eco RI fragment demonstrated reduced autoradiographic intensity in the 12q- sample compared with several normal controls. These findings indicate that the genomic location for one of the highly or perfectly homologous 2.2-kb Eco RI fragments is in chromosome region 12q21q22, and suggest that a low-copy repetitive DNA probe as used here may have practical utility, as in detecting small deletions or other chromosome alterations.

Animals↗
PubMed1984

Frequency of reactivation and variability in expression of X-linked enzyme loci.

A mouse-human cell hybrid clone retaining an inactive human X chromosome was treated with 5-azacytidine. Following treatment, expression of the X-linked enzyme markers, hypoxanthine-guanine phosphoribosyltransferase (HPRT), glucose-6-phosphate dehydrogenase (G6PD), phosphoglycerate kinase (PGK), and alpha-galactosidase A (GLA) was examined. Results presented here show that 45 of the 62 clones positive for human HPRT expressed human GLA, while only four of 68 clones negative for human HPRT expressed human GLA. These results strongly suggest that there is coordinate reactivation of GLA and HPRT. Reactivated expression of G6PD was studied in detail. The studies show that 5-azacytidine can induce heritable changes in the inactive human X chromosome resulting in the expression of G6PD activity at a level lower than that from an active human X chromosome.

Animals↗
PubMed1984

Aniridia: enzyme studies in an 11p--chromosomal deletion.

A patient with aniridia and an interstitial deletion of the bands p13-p14 of the short arm of chromosome 11 was studied to determine the relative locations of the gene(s) encoding for the aniridia-Wilms' tumor association with other genes on the same chromosome. Quantitative analysis was performed on the red blood cell enzymes lactic acid dehydrogenase-A (LDH-A) and catalase, the genes for which are located on the short arm of chromosome 11. The activity of LDH-A was normal; the activity of catalase was reduced to approximately half normal. This evidence supports loci for the genes encoding for both catalase and the aniridia-Wilms' tumor association within the bands p13-p14 of the short arm of chromosome 11; the normal activity of LDH-A supports a locus outside this region.

Catalase↗