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Biomedical subjects

A Andreas

Publications and source records attributed to A Andreas.

14 recordsLinked to original sources
PubMed1992

An approach to the localization of the susceptibility genes for generalized myasthenia gravis by mapping recombinant ancestral haplotypes.

The association of HLA A1, B8, and DR3 with generalized myasthenia gravis (GMG) in Caucasoids is well established, but no particular gene has been implicated and there is still no adequate explanation in functional terms. In this study we have taken advantage of sequential genomic markers between B8 and DR3 so as to map the location of susceptibility gene(s) on the A1, B8, DR3 (8.1) ancestral haplotype. By studying 51 patients, we have delineated a region between HLA B and TNF which is shared by 29/29 patients with B8 and DR3, 19/19 patients with B8 but not DR3 and 2/3 patients with DR3 but not B8. The potential importance of this region was confirmed by examining a similar disease induced by D-Penicillamine (D-PenMG) and associated with different HLA class II alleles (DR1 and/or DR7). Among these patients, 7/16 (44%) have B8, often with other markers of 8.1. These results implicate at least two categories of genes in determining susceptibility to MG; one located in the region between HLA B and TNF may be immunoregulatory, whereas the second, located in the class II region, may relate to the inducing factor (e.g., DR1 or DR7 in D-PenMG).

Blotting, Southern↗
PubMed1991

Prenatal diagnosis of 21-hydroxylase deficiency by RFLP analysis of the 21-hydroxylase, complement C4, and HLA class II genes.

In 19 pregnancies at risk for 21-hydroxylase deficiency (21OHD) in 18 families with at least one affected child, prenatal diagnosis was performed by RFLP analysis using the enzymes Taq I and EcoRI and the DNA probes specific for the 21OH genes, the closely linked complement C4 genes and the highly polymorphic HLA class II genes DRB, DQB, and DPB. For fetal DNA analysis either chorionic villi or cultivated amniotic cells were used. In all 19 cases, a clear prenatal diagnosis was possible either with the 21OH probe alone or in most cases, by combining the results of the different closely linked loci.

Adrenal Hyperplasia, Congenital↗
PubMed1991

A model for the role of HLA-DQ molecules in the pathogenesis of juvenile chronic arthritis.

Restriction fragment length polymorphism (RFLP) typing of MHC-class II loci DRB, DQA1, DQB1, DQA2 and DPB1 was performed in 94 patients with seronegative juvenile chronic arthritis (JCA) and 184 random controls. Analysis of allele frequencies and MHC-class II 4-loci haplotypes indicate: (1) Susceptibility to JCA is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion, especially in early onset pauciarticular JCA (EOPA-JCA). (2) Haplotype and sequence analysis show two independent MHC-class II associations for susceptibility to EOPA-JCA, one located in DQA1, the other in DPB1. (3) Two RFLP defined patterns of the DQA1 locus, DQA1.5 (DQA1*0501) and DQA1.8 (DQA1*0401, *0601) are strongly associated with the disease. (4) Analysis of amino-acid (AA) sequences coded in exon 2 of DQA1 reveals an AA sequence of six AAs common to all three associated DQA1 alleles. This suggests a model that includes a functional role for HLA-DQ molecules in the pathogenesis of JCA.

Alleles↗
PubMed1991

Nonradioactive HLA class II typing using polymerase chain reaction and digoxigenin-11-2'-3'-dideoxy-uridinetriphosphate-labeled oligonucleotide probes.

We describe a new, simple, rapid, and sensitive nonradioactive technique for the analysis of genetic variations. Genomic DNA was amplified using polymerase chain reaction and amplified DNA was hybridized, with digoxigenin (DIG)-labeled sequence-specific oligonucleotides. High specificity and sensitivity was achieved when labeling the sequence-specific oligonucleotide at the 3' end with only one DIG using digoxigenin-11-2',3'-dideoxy-uridine-5'-triphosphate and DNA deoxynucleotidylexotransferase. The hybridized probes were detected using antidigoxigenin alkaline phosphatase, fab fragments, and X-phosphate/NBT for visualization. This method was applied to the analysis of HLA-DR4-DRB1 alleles in polymerase chain reaction-amplified genomic DNA and resulted in highly specific and sensitive hybridization signals discriminating even in cases of a one-base-pair mismatch. This technique is particularly suited for HLA oligotyping because it allows the use of tetramethylammonium chloride for the simplification of hybridization and washing conditions.

Base Sequence↗
PubMed1990

Hypervariability of intronic simple (gt)n(ga)m repeats in HLA-DRB genes.

We have investigated the extent of DNA variability in intronic simple (gt)n(ga)m repeat sequences and correlated this to sequence polymorphisms in the flanking exon 2 of HLA-DRB genes. The polymerase chain reaction (PCR) was used to amplify a DNA fragment containing exon 2 and the repeat region of intron 2. The PCR products were separated on sequencing gels in order to demonstrate length hypervariability of the (gt)n(ga)m repeats. In a parallel experiment, the PCR products were cloned and sequenced (each exon 2 plus adjacent simple repeats) to characterize the simple repeats in relation to the HLA-DRB sequences. In a panel of 25 DRB1, DRB4, and DRB5 alleles new sequences were not detected. Restriction fragment length polymorphism (RFLP) subtyping of serologically defined haplotypes corresponds to translated DNA sequences in 85% of the cases, the exceptions involving unusual DR/DQ combinations. Many identical DRB1 alleles can be distinguished on the basis of their adjacent simple repeats. We found group-specific organization of the repeats: the DRw52 supergroup repeats differ from those of DRB1*0101, DRB4*0101, and DRB5*0101 alleles and from those of pseudogenes. Finally, we amplified baboon DNA and found a DRB allele with extensive similarity to DRB1 sequences of the DRw52 supergroup. The simple repeat of the baboon gene, however, resembles that of human pseudogenes. In addition to further subtyping, the parallel study of polymorphic protein and hypervariable DNA alleles may allow conclusions to be drawn on the relationships between the DRB genes and perhaps also on the theory of trans-species evolution.

Amino Acid Sequence↗
PubMed1990

[DNA analysis of HLA class II and III genes in sudden infant death (SIDS)].

In 39 cases of SID we studied the polymorphism of HLA-class II genes DRB and DQB and HLA-class III genes C4 (C4A and C4B, genes encoding the fourth complement component) and 21-hydroxylase (21OH-A and 21OH-B, genes encoding the enzyme 21-hydroxylase of the cortisol pathway) by DNA analysis. This study was performed in cooperation with the Institute of Legal Medicine, University of Munich. Compared to healthy controls the percentage of C4B gene deletions, C4B gene duplications (C4B "short") and 21OH-A gene deletions is increased in SIDS. The deviations are statistically not significant. The analysis of the HLA-DR alleles revealed a significant decrease of HLA-DR2 in SIDS compared to controls (p = 0.0016, pc = 0.016). The results of this study indicate a possible role of C4B/21OH-A gene defects as a risk factor in a subgroup of SID cases. This hypothesis has to be confirmed by studying further cases.

Chromosome Aberrations↗
PubMed1985

Osteopetrosis.

Explore the source record for details and available documents.

Child, Preschool↗
PubMed1983

Multiple sclerosis: immunogenetic analyses of sib-pair double case families. II. Studies on the association of multiple sclerosis with C2, C4, BF, C3, C6, and GLO polymorphisms.

The complement component polymorphisms of C2, C4, BF, C3, C6, and the enzyme polymorphism GLO were studied in 13 sib-pair double case families with multiple sclerosis. A significant association was seen between MS patients and the C4 haplotype A4,B2 as compared with their healthy siblings. This finding seems to parallel reports on C2 hypocomplementemia in MS patients since C4 A4,B2 in normal individuals was also seen to be in linkage disequilibrium with the C2 deficiency allele (C2QO) by other investigators.

Complement C2↗
PubMed1977

B- and T-cell-specific alloantigens in man.

Screening for B-cell-specific antibodies in unabsorbed pregnancy sera preselected for weak reactivity in regular HLA-A, -B, and -C screening yielded a relatively high proportion (35/81) of B-cell-specific antibodies. Most B-cell-specific antibodies react broadly, showing inclusion phenomena suggesting 'cross-reactivity' analogous to that observed in HLA-A and -B serology. In control experiments with T-cell-enriched suspensions three antisera reacted with T cells and not with B cells. These antisera are highly associated with HLA-A2 in the unrelated population and segregate with HLA haplotypes in families and with HLA-A in a family with HLA-A, B recombination, Thus it appears that the human equivalents of Ia antigens may include--in analogy to the murine Ia antigens--B cell- as well as T-cell-specific alloantigens.

Antibody Specificity↗
PubMedDate not supplied

Non-radioactive oligotyping for HLA-DR1-DRw10 using polymerase chain reaction, digoxigenin-labelled oligonucleotides and chemiluminescence detection.

We describe a rapid non-radioactive DNA typing of the serological types DR1-DRw10 using polymerase chain reaction (PCR)-amplified DNA and 15 sequence-specific oligonucleotides (SSO) which are labelled enzymatically at their 3' end with one digoxigenin (DIG). The hybridized SSOs were detected using anti-DIG alkaline phosphatase and Fab fragments and visualization was obtained with the chemiluminescent substate 3-(2'-spiroadamantan)-4-(3''-phosphoryloxy)-phenyl-1,2-di o xetan (AMPPD). The results were identical with those of the previously used 5-bromo-4-chloro-3-indolyl-phosphate (BCIP)/4-nitrobluetetrazolium chloride (NBT) system. The use of AMPPD is more rapid and allows the repeated rehybridization of the membrane-bound DNA.

Base Sequence↗