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G Daniels

Publications and source records attributed to G Daniels.

At least 55 records · Page 3Linked to original sources
PubMed1994

Serotype switching in a partially deleted RHD gene.

We have studied the RH genes in donors with the RhD-negative haplotype dCes. In contrast to the usual arrangement of genes in RhD-negative individuals, where the lack of antigen expression is due to deletion of the entire RHD gene, we find that the dCes haplotype includes an RHD gene with an internal deletion. Moreover, there appear to be no 5' sequences characteristic of RHC suggesting that the RhC antigen may be encoded by a truncated RHD or a recombinant RHD/CE gene in these dCes/dce genomes.

Base Sequence↗
PubMed1994

Lack of RH C/E expression in the Rhesus D--phenotype is the result of a gene deletion.

We have investigated the arrangement of genes in the rare Rh (Rhesus) partial null condition D--. Southern blot and PCR studies under conditions which distinguish the highly homologous RH D and RH C/E genes show that in an Icelandic family with the D-- haplotype at least 85% of the RH C/E gene is deleted. This finding is in contrast to one other published case of this phenotype, where intact RH D and C/E genes were found, and also to the full amorph Rhnull phenotype, where an intact RH C/E gene was found, accompanied by the deletion of the RH D gene typical of Rh D-negative individuals.

Base Sequence↗
PubMed1994

Mg+ MNS blood group phenotype: further observations.

Red cells carrying the low-frequency MNS antigen Mg reacted with the only example of anti-DANE, an antibody which had previously defined the GP. Dane (Mi.IX) phenotype. Furthermore, Mg+ cells reacted with the original anti-Mur (serum of Mrs. Murrell), but with none of 14 other anti-Mur. Therefore, Mg+ cells carry both DANE antigen and an atypical Mur antigen. Immunoblotting of membranes from Mg+ cells with anti-M, and with eluates prepared from anti-Mg and Mrs. Murrell's serum demonstrated a glycophorin A (GPA) molecule whose mobility was increased by an apparent M(r) of about 3,000 presumably due to the loss of the three O-glycans known to be absent from Mg-active GPA.

Amino Acid Sequence↗
PubMed1993

Alteration of splice site selection by an exon mutation in the human glycophorin A gene.

We report the identification in human glycophorin A gene of a novel exon mutation that affects splice site selection. DNA mapping showed that the mutation has abolished a unique MspI site marking the exon III-intron 3 splice junction (ACCG/GT). Genomic sequencing confirmed the occurrence of a single G-->A transition at the terminal nucleotide position of exon III. Analysis of the mRNA composition demonstrated a partial inactivation of the altered 5' splice site as well as skipping of exons involving the alternative use of other constitutive splice sites. The full-length transcript with the cognate A change encodes a variant glycophorin with an arginine replacing a glycine at position 59 and defining the ERIK epitope, whereas the exon III-deleted transcript specifies a shorter glycophorin carrying the Sta antigen. Also identified were the misspliced mRNA species with exon I-IV and exon I-V connections generated by selection of 5' splice sites far distant from the mutated site. Although having a correct translation frame, the predicted polypeptides of such exon-skipping products were not assembled on the erythrocyte membrane probably due to the severe truncation of the signal sequence required for targeting and translocation. These observations reveal a new mechanism for antigenic diversity of human glycophorins.

Alternative Splicing↗
PubMed1993

A point mutation in the GYPC gene results in the expression of the blood group Ana antigen on glycophorin D but not on glycophorin C: further evidence that glycophorin D is a product of the GYPC gene.

Glycophorin C (GPC) and glycophorin D (GPD) are homologous sialoglycoproteins in the human red blood cell membrane. Both are thought to be encoded by the GPC gene (GYPC). We report that the rare blood group antigen, Ana, is expressed on GPD but not on GPC. cDNA was synthesized from total RNA obtained from two unrelated, heterozygous Ana+ blood donors and analyzed by the polymerase chain reaction using primers that spanned sequences encoded by the GYPC gene. The expected 412-bp fragment was generated, and sequencing of the amplified product showed a G-->T substitution at nucleotide 67 of the coding sequence, resulting in the substitution of alanine by serine at amino acid residue 23 of GPC and, presumably, residue 2 of GPD. To explain the expression of Ana on GPD but not on GPC, we postulate that the conformation of the amino acid residues at the N-terminal region of GPD determines the antigenic expression as this conformation would be different from that of the same sequence of amino acids occurring within GPC. Other possible reasons for antigen expression on a shorter protein product but not on the full-length protein product of the same gene are discussed. We extrapolate this reasoning to account for the expression of the common GE2 blood group antigen on GPD but not on GPC.

Amino Acid Sequence↗
PubMed1993

Rh null phenotypes are not due to a gross deletion and can occur on different Rh genetic backgrounds.

Alu element-primed PCR was performed on genomic clones containing human RH blood group genes. When used as a probe, the Alu PCR product detected a restriction fragment-length polymorphism which is in complete linkage disequilibrium with the Rh C/c serological polymorphism, irrespective of the Rh D or E serological type it is coupled with. This provides the opportunity to type individuals for their RH C gene directly at the DNA level. RFLP analysis of two individuals with the amorph Rh null phenotype revealed that in one case this phenotype occurred on an RH C background, whereas in the other it was on an RH c background. Taken together these results indicate that the Rh C/c polymorphism has arisen only once, but that the amorph Rh null phenotype, although exceedingly rare, is the result of at least two independent mutations.

Alleles↗
PubMed1993

Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life. V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Two new questionnaires concerning the quality of life of patients with heart failure were used in a randomized, controlled trial to determine if the patients' perceptions of the effects of enalapril on their daily activities and sense of well-being were different from those of a group treated with hydralazine and isosorbide dinitrate. METHODS AND RESULTS: The questionnaires were completed at baseline and at 3 months, 6 months, and subsequently every 6 months during follow-up, which averaged 2.5 years (range, 0.5-5.7 years). Data from the questionnaires were reliable as indicated by correlation coefficients between repeated baseline scores of 0.88 and 0.87. Both treatment groups showed a progressive deterioration in quality of life as measured by both questionnaires. The questionnaire scores of the two treatment groups were not significantly different at any follow-up visit. Furthermore, there were no differences between treatments among subgroups defined by baseline questionnaire scores, peak oxygen consumption, ejection fraction, previous vasodilator use, and plasma norepinephrine concentration. CONCLUSIONS: Although several factors may limit the generalization of these results, the lack of a difference with regard to patients' quality of life is an important consideration for the evaluation of the relative therapeutic efficacy of these vasodilators.

Attitude to Health↗
PubMed1992

Molecular analysis of human glycophorin MiIX gene shows a silent segment transfer and untemplated mutation resulting from gene conversion via sequence repeats.

The human glycophorin (HGp) loci that define the red blood cell surface antigens of the MNSs blood group system exhibit considerable allelic variation. Previous studies have identified gene conversion events involving HGpA(alpha) and HGpB(delta) that produced delta-alpha-delta hybrid genes which differ in the location of breakpoints. This report presents the molecular analysis of HGpMilX, the first example of a reverse alpha-delta-alpha hybrid gene that specifies a newly described phenotype of the Miltenberger complex. A novel restriction fragment unique to the HGpMilX gene was detected by Southern blot hybridization. The structure of the genomic region encoding the entire extracellular domain of the MilX protein was determined. Nucleotide sequencing of amplified genomic DNA showed that a silent segment of the HGpB(delta) gene had been transposed to replace the internal part of exon III in the HGpA(alpha) gene, thereby resulting in the formation of the MilX allele with an alpha-delta-alpha configuration. The proximal alpha-delta breakpoint was found to be flanked by a direct repeat of the acceptor splice site, whereas the distal delta-alpha breakpoint was localized to a palindromic region. This DNA rearrangement, with a minimal transfer of 16 templated nucleotides and a single mutation of untemplated adenyl nucleotide, not only created two intraexon hybrid junctions but transactivated the expression of a new stretch of amino acid residues in the MilX protein. Such a segment replacement may have occurred through the directional transfer from one duplex to the other via the mechanism of gene conversion. The occurrence of HGpMilX as another hybrid derived from parts of parent genes underlines the role of the recombinational "hotspot" in the generation of allelic diversity in the glycophorin family.

Amino Acid Sequence↗
PubMed1992

Effect of enzymes on and chemical modifications of high-frequency red cell antigens.

Enzyme or chemical modification of intact red cells results in the destruction of some blood group antigens. The pattern of reactions of an antibody with red cells treated with various proteinases, with sialidase, and with the disulfide bond-reducing agent 2-aminoethylisothiouronium bromide (AET) can aid in antibody identification. This information can prove particularly beneficial with antibodies to antigens of very high frequency, where antigen- negative cells may be difficult to obtain. Provided in this article is a table listing most of the authenticated high-frequency red cell antigens and the effect on those antigens of trypsin, chymotrypsin, a mixture of trypsin and chymotrypsin, papain, pronase, sialidase, and AET.

Journal Article↗
PubMed1991

Miltenberger class IX of the MNS blood group system.

Mi.IX is a new phenotype in the Miltenberger series of the MNS blood group system with a frequency of 0.43% in Denmark. Mi.IX red cells are Mur+ but do not express any of the other established Miltenberger determinants. They react with a new antibody, anti-DANE, which defines a determinant present on Mi.IX cells but not on cells of other Miltenberger phenotypes. Four Mi.IX propositi have been found. Their families show that MiIX is inherited with a MS complex (lod score 3.69 at theta = 0.00) which produces a trypsin-resistant M antigen. DANE has been allotted the ISBT number 002032 (MNS32). Serological and immunochemical studies with human and monoclonal antibodies to various determinants on glycophorin A (GPA) suggest that Mi.IX is associated with an aberrant GPA molecule that lacks the trypsin cleavage site at amino-acid residue 39, retains the chymotrypsin cleavage site at residue 34 and has an apparent Mr of about 1,000 less than normal GPA. It is proposed that this Mi.IX molecule has an amino acid and possibly also a glycosylation change in the region of amino-acid residues 35-39.

Adult↗
PubMed1990

Evidence that the Auberger blood group antigens are located on the Lutheran glycoproteins.

Immunoblots of red cell membranes stained with eluates of alloanti-Aua and alloanti-Aub show that these antibodies recognize 2 membrane components from Au(a+) and Au(b+) cells, respectively. These structures, of apparent molecular weight (Mr) 79,000 and 85,000, are identical in appearance and mobility on a 10% SDS polyacrylamide gel to the Lutheran glycoproteins identified by alloanti-Lub. Like the Lutheran glycoproteins, they showed a reduction in apparent Mr of about 1,500 after sialidase treatment. Red cell membrane components immunoprecipitated by a Lutheran-related monoclonal antibody, were analysed with Lutheran and Auberger antibodies by immunoblotting. The Lutheran glycoproteins were revealed by anti-Lub in precipitates from Au(a+b-) Lu(a-b+) and Au(a-b+) Lu(a-b+) cells, by anti-Aua in precipitates from Au(a+b-) Lu(a-b+) cells and by anti-Aub in precipitates from Au(a-b+) Lu(a-b+) cells. The same components were also recognized by anti-Lua in precipitates from Lu(a+b-) cells. Thus Aua and Aub antigens appear to be carried on the same red cell membrane structures as those carrying the Lutheran determinants. These results are particularly significant in the light of the very close phenotypic association between the Auberger and Lutheran blood groups which have been shown, by one family, to be controlled by genes at separate loci.

Blood Group Antigens↗
PubMed1989

Identification, by immunoblotting, of the structures carrying Lutheran and para-Lutheran blood group antigens.

Immunoblotting was performed, after sodium dodecyl sulphate polyacrylamide gel electrophoresis of solubilised red cell membranes under non-reducing conditions, with human Lutheran antibodies, anti-Lua, -Lub, -Lu3, -Lu6 and -Lu8, and with human para-Lutheran antibodies, -Lu4, -Lu12 and -Lu17. On antigen-positive red cells all antibodies revealed two components of apparent molecular weight (Mr) 83,000 and 76,000. Anti-Lua and -Lub gave no bands with Lu(a-b+) or Lu(a+b-) cells, respectively. With the exception of anti-Lu17, which reacted normally, and anti-Lu3, which reacted weakly, none of the antibodies showed bands with membranes from Lu(a-b-) cells of the In(Lu) type. Treatment of the red cells with sialidase led to a small reduction in the apparent Mr of the Lutheran glycoproteins which, therefore, appear to contain sialic acid bearing O-linked oligosaccharides.

Erythrocyte Membrane↗
PubMed1989

Cromer-related antigens--blood group determinants on decay-accelerating factor.

Cromer-related antigens, a series of blood group antigens phenotypically related to each other through various serological characteristics, have recently been shown to be carried on the complement regulatory glycoprotein decay-accelerating factor (DAF). Cromer-related antigens, therefore, represent a number of inherited variants and polymorphisms of DAF. The Inab phenotype, a 'Cromer-null' phenotype in which the red cells lack all Cromer-related antigens, appears to be an inherited DAF deficiency.

Antibodies, Monoclonal↗