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Biomedical subjects

S A Jordan

Publications and source records attributed to S A Jordan.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cadmium disposition and metallothionein induction in mice: strain-, sex-, age- and dose-dependent differences.

The strain- and sex-related differences in tissue cadmium (Cd) and metallothionein (MT) levels were examined in young adult (4-6 months old) C3H/HeJ, DBA/2J, 129/J, CD-1 and A/J mice, 24 h after a subcutaneous (s.c.) injection of 5-30 mumol CdCl2/kg. In many cases the tissue Cd concentrations were inversely related to the tissue weights. Also, the strain and sex differences were more obvious at 20-30-mumol dose levels. At such doses the hepatosensitive C3H males had as much as 30% higher hepatic Cd concentrations as the resistant DBA males, but similar concentrations to the resistant A/J and CD-1 males. This observation suggests that tissue Cd level is not the only determinant of strain differences in hepatotoxicity in males. Among the females, the A/J had 30-47% higher hepatic Cd concentration than the other strains. Livers of male C3H, CD-1 and 129/J mice had 17-57% higher Cd concentrations than those of the females; the greatest difference was in the C3H strain in which only the males exhibited hepatotoxicity at the 30 mumol dose. In all animals the hepatic MT concentration increased with the increasing Cd concentration. However, the 129/J males and all the females reached a plateau in MT concentration at Cd concentrations of 20-30 micrograms/g liver. Even at the highest Cd concentration, the C3H males had MT concentrations similar to some of the hepatoresistant males, suggesting that their sensitivity to Cd was not due to compromised MT levels. The renal Cd concentration was similar in males of most strains but not in females. For example, at the 30-mumol dose 129/J females had a Cd concentration which was 70% higher than in the DBA females. Also, at this dose level the A/J, C3H and 129/J females had 30-50% more Cd than the males. The DBA and C3H males had approximately twice the MT concentration of the A/J and 129/J males at 10 micrograms Cd/g kidney. At similar Cd concentration, the DBA females also had 1.6-2.0 times the MT concentration of the other females. The renal MT levels in females were 1.4-2.9 times higher than in males. Strains susceptible to the testicular toxicity of Cd had up to three times greater testicular Cd accumulation than the resistant strains. However, there was no increase in testicular MT in any strain. The effect of age on Cd and MT levels was studied in 19-month-old A/J and DBA mice at the 25-mumol dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1993

A mutation (Met-->Arg) in the type I keratin (K14) gene responsible for autosomal dominant epidermolysis bullosa simplex.

We have identified a single base change in exon 4 of the type I keratin gene which results in the replacement of a methionine for an arginine residue at codon 272 in an Irish family displaying an autosomal dominant simplex (Koebner) form of epidermolysis bullosa (EB). This family had previously provided tentative evidence for linkage to genetic markers on chromosome 1q. The mutation cosegregates with the disease, producing a lod score of 4.8 at theta = 0.

Amino Acid Sequence↗
PubMed1993

Localization of an autosomal dominant retinitis pigmentosa gene to chromosome 7q.

Retinitis pigmentosa is a group of clinically and genetically heterogeneous retinopathies and a significant cause of worldwide visual handicap. We have typed DNA from members of a Spanish family segregating an autosomal dominant form of retinitis pigmentosa (adRP) using a large series of simple sequence polymorphic markers. Positive two-point lod scores have been obtained with fifteen markers including D7S480 (theta max = 0.00, Zmax = 7.22). Multipoint analyses using a subset of these markers gave a lod score of 7.51 maximizing at D7S480. These data provide definitive evidence for the localisation of an adRP gene on chromosome 7q, and highlight the extensive genetic heterogeneity that exists in the autosomal dominant form of this disease.

Adolescent↗
PubMed1992

Polymorphic variation within "conserved" sequences at the 3' end of the human RDS gene which results in amino acid substitutions.

The human RDS gene, previously mapped to chromosome 6p, encodes a protein found in the outer disc membrane of the photoreceptor cells of the retina. The cDNA sequence of the human gene shows 85% identity with the bovine peripherin gene and the rds (retinal degeneration slow) genes from mouse and rat. Mutations in the RDS gene have recently been implicated in autosomal dominant retinitis pigmentosa (adRP) in some families. Here we present evidence that the third exon of this gene is subject to polymorphic variation in humans. The three sequence alterations described in this paper give rise to amino acid substitutions. However, as these missense mutations also occur in the normal population they are not implicated as causing adRP. Interestingly such sequence variation is not found within other species examined including mouse and bovine. These intragenic polymorphisms will be of future potential value in studies to locate further disease causing mutations in adRP patients in the RDS gene.

Amino Acid Sequence↗
PubMed1992

Autosomal dominant retinitis pigmentosa: a novel mutation at the peripherin/RDS locus in the original 6p-linked pedigree.

Using single-strand conformation polymorphism electrophoresis, heteroduplex analysis, and direct sequencing, we have searched for possible disease-causing mutations in the adRP family in which we originally found tight linkage of the disease to 6p. We have now identified a single base change in exon 2, which results in the replacement of a serine residue at codon 212 for a glycine residue. The mutation cosegregates with the disease with a lod score of 12.1 at theta = 0.0.

Amino Acid Sequence↗
PubMed1992

Mapping of bovine markers CYP21, PRL, and BOLA DRBP1 by genetic linkage analysis in reference pedigrees.

We have analyzed DNA from 13 bovine reference pedigrees using primers specific for microsatellite markers derived from the 21-steroid hydroxylase (CYP21) and prolactin (PRL) genes and the leukocyte antigen (BOLA DRBP1) pseudogene. Linkage was demonstrated between PRL and BOLA DRBP1 (theta = 0.05; Z = 19.6), cyp21 and PRL (theta = 0.13; Z = 6.8), and BOLA DRBP1 and CYP21 (theta = 0.17; Z = 10.4). These results suggest an order BOLA DRBP1-PRL-CYP21, although in a multilocus analysis the alternative order PRL-BOLA DRBP1-CYP21 was also possible. The data confirm and extend the previously established syntenic relationship between these markers on bovine chromosome 23 and provide points of anchorage for further linkage studies in the reference pedigrees described.

Animals↗
PubMed1992

Autosomal dominant retinitis pigmentosa (adRP): exclusion of a gene from three mapped loci provides evidence for the existence of a fourth locus.

Retinitis Pigmentosa (RP) is a group of inherited retinopathies which affect approximately 1 in 4,000 individuals. The disorder can be classified on the basis of inheritance; dominant, recessive and X-linked forms have been well documented. The existence of genetic heterogeneity within autosomal dominant RP (adRP) had been previously demonstrated. As a result of extensive linkage studies in 2 large Irish families and 1 American pedigree three adRP genes have been mapped. adRP genes have been localised to chromosome 3q close to the rod photoreceptor gene, rhodopsin; to chromosome 6p close to another transmembrane photoreceptor gene, peripherin/RDS and to the pericentric region of chromosome 8, although the causative gene in this region has not yet been identified. Here we report the results of a linkage study in a Spanish family, who exhibit an early-onset form of adRP. The adRP gene segregating in this family has been excluded from the three known adRP loci on chromosomes 3q, 6p and 8 using a series of both intragenic microsatellite markers from the rhodopsin and peripherin/RDS genes and markers flanking the three known loci. These results provide definitive evidence for the existence of a fourth adRP locus, further emphasising the genetic heterogeneity that exists within adRP.

Chromosome Mapping↗
PubMed1992

Autosomal dominant retinitis pigmentosa (adRP; RP6): cosegregation of RP6 and the peripherin-RDS locus in a late-onset family of Irish origin.

We recently reported the localization of a gene for late-onset autosomal dominant retinitis pigmentosa (adRP; RP6), on the short arm of chromosome 6, by linkage analysis in a large family of Irish origin. It is notable that the gene encoding peripherin-RDS, a photoreceptor-specific protein, recently has been physically mapped on 6p. In our own analysis, an intrageneic marker derived from this gene cosegregated with the adRP disease locus with zero recombination (lod score 5.46 at q = .00). Using the CEPH reference panel, we now report the mapping of the peripherin-RDS gene relative to other 6p markers in the CEPH data base. Incorporation of these data into a multipoint analysis produced a lod score for adRP of 8.21, maximizing at the peripherin-RDS locus. This study provides strong evidence suggesting a role for peripherin-RDS in the etiology of one form of adRP.

Base Sequence↗
PubMed1991

A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa.

The group of retinopathies termed retinitis pigmentosa (RP) greatly contribute to visual dysfunction in man with a frequency of roughly 1 in 4,000. We mapped the first autosomal dominant RP (adRP) gene to chromosome 3q, close to the gene encoding rhodopsin, a rod photoreceptor pigment protein. Subsequently, mutations in this gene have been implicated as responsible for some forms of adRP. Another adRP gene has been mapped to chromosome 8p. A third adRP gene in a large Irish pedigree has been mapped to chromosome 6p, showing tight linkage with the gene for peripherin, a photoreceptor cell-specific glycoprotein, which is thus a strong candidate for the defective gene. We have now identified a three-base-pair deletion which results in the loss of one of a pair of highly conserved cysteine residues in the predicted third transmembrane domain of peripherin. This deletion segregates with the disease phenotype but is not present in unaffected controls, and suggests that mutant peripherin gives rise to retinitis pigmentosa.

Amino Acid Sequence↗
PubMed1991

Autosomal dominant retinitis pigmentosa: a new multi-allelic marker (D3S621) genetically linked to the disease locus (RP4).

We report the characterization of a new eight-allele microsatellite (D3S621) isolated from a human chromosome 3 library. Two-point and multi-locus genetic linkage analysis have shown D3S621 to co-segregate with the previously mapped RP4 (theta m = 0.12, Zm = 4.34) and with other genetic markers on the long arm of the chromosome, including D3S14 (R208) (theta m = 0.00, Zm = 15.10), D3S47 (C17) (theta m = 0.11, Zm = 4.95), Rho (theta m = 0.07, Zm = 1.37), D3S21 (L182) (theta m = 0.07, Zm = 2.40) and D3S19 (U1) (theta m = 0.13, Zm = 2.78). This highly informative marker, with a polymorphic information content of 0.78, should be of considerable value in the extension of linkage data for autosomal dominant retinitis pigmentosa with respect to locii on the long arm of chromosome 3.

Alleles↗