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Biomedical subjects

L J Ward

Publications and source records attributed to L J Ward.

13 recordsLinked to original sources
PubMed1991

Tight linkage of the gene for spinocerebellar ataxia to D6S89 on the short arm of chromosome 6 in a kindred for which close linkage to both HLA and F13A1 is excluded.

A locus for an autosomal dominant form of spinocerebellar ataxia (SCA1) has been assigned to the short arm of chromosome 6 on the basis of linkage to the major histocompatibility system (HLA). In this study of a five-generation American black family, close linkage between the disease locus and both HLA and the coagulation factor XIIIA (F13A1) locus was excluded, and lod scores for all locations of the disease locus between HLA and F13A1 were less than -1.4. These results suggest that the locus causing spinocerebellar ataxia in this family is not in this region. However, the disease locus was found to be closely linked to a microsatellite polymorphism, D6S89, which is between HLA and F13A1. The maximum lod score for SCA1 and D6S89 is 4.90 at a recombination fraction of 0, both in males and in females. These data show that exclusion of close linkage to the HLA complex and F13A1 in a kindred with spinocerebellar ataxia does not rule out the possibility that the disease locus in that family is on 6p. Accordingly, all families segregating a dominantly inherited ataxia should be evaluated for linkage to D6S89, to determine whether the locus causing the disease is SCA1.

Adolescent↗
PubMed1990

Gametic equilibrium between 24 polymorphic markers.

Pairs of unlinked genetic markers (blood cell antigens and enzymes and serum proteins) were tested for gametic equilibrium (GE) in data from 508 unrelated individuals from different regions of North America. A total of 24 markers were considered in the study. Only 14 of 262 pairs (5.3%) of markers deviated from GE at the 5% significance level and only 6 pairs (2.3%) remained in significant disequilibrium after accounting for genetic heterogeneity among regional groups. The particular combinations of alleles or one-locus genotypes that showed significant association were identified in case they might be replicated in future studies. On the basis of this study alone, however, there is no reason to suspect disequilibrium between the pairs of markers studied.

Alleles↗
PubMed1989

"Acadian" and "classical" forms of Friedreich ataxia are most probably caused by mutations at the same locus.

"Acadian ataxia" is a form of Friedreich ataxia found in individuals of Acadian ancestry. It was described by Barbeau (in Sobue I (ed): Spinocerebellar Degeneration; Tokyo: Univ. Tokyo Press, pp 121-142, 1980) as having a slower course of degeneration and less severe secondary symptoms than "classical" Friedreich ataxia. He suggested that these 2 forms of the disease may be distinct. The mutation causing "classical" Friedreich ataxia has recently been mapped to chromosome 9 through genetic linkage studies, and here we show that the locus causing Friedreich ataxia in Acadian families from southwestern Louisiana is tightly linked to the same DNA marker, D9S15. Thus, these 2 disorders, which may be differentiated clinically, are most probably due to mutation(s) at the same locus on chromosome 9.

Chromosome Mapping↗
PubMed1989

Characterization of a monoclonal antibody against active pectate lyase from Erwinia carotovora.

A monoclonal antibody (2E2) produced against pectate lyase from Erwinia carotovora ssp. carotovora reacted with a 41- and a 44-kilodaltion protein on Western blots of concentrated Erwinia culture supernatants resolved by sodium dodecyl sulfate - polyacrylamide gel electrophoresis. It was unequivocally shown that monoclonal 2E2 reacted with an active form of pectate lyase by affinity purifying the antigen with the monoclonal. The affinity-purified antigen was enzymatically active and moved as a single protein band in a nonequilibrium isoelectric focusing gel. Monoclonal 2E2 reacted with the pectate lyases of a diverse range of E. carotovora ssp. carotovora, ssp. atroseptica, and ssp. betavasculorum strains, as well as with one of three strains of E. chrysanthemi. The electrophoretic mobility of the major protein (44 kilodaltons) that reacted with 2E2 was identical within a subspecies but differed among subspecies.

Antibodies, Bacterial↗
PubMed1987

A linkage study of panic disorder.

We tested for linkage between panic disorder and a battery of 29 genetic markers in 26 families. Linkage between panic disorder and 18 of the marker loci could be excluded at a recombination fraction of 0.00, nine at a recombination fraction of 0.05, and four at a recombination fraction of 0.10. The 18 loci are distributed over ten chromosomes. One locus was suggestive of linkage. The maximum lod score for alpha-haptoglobin was 2.27 at a recombination fraction of 0.0, representing odds in favor of linkage of 186.1. alpha-Haptoglobin has been mapped to chromosome 16q22. The results demonstrate that linkage studies of psychiatric disorders can yield informative results by identifying tentative linkages that merit further investigation and by excluding regions of the genome from future linkage searches.

Adult↗
PubMed1987

Linkage and segregation analyses of apolipoproteins A1 and B, and lipoprotein cholesterol levels in a large pedigree with excess coronary heart disease: the Bogalusa Heart Study.

Robust methods were employed, using data from a single large pedigree, to screen serum apolipoprotein A1 and B levels, serum lipoprotein cholesterol levels, and ratios of serum lipoprotein cholesterol fractions to apolipoprotein A1 and B levels for genetic linkage to 31 polymorphic markers. Segregation analyses were performed for each of the apolipoprotein and lipoprotein cholesterol fractions to obtain estimates for use in applying likelihood methods of linkage analysis. Trait-marker combinations for which linkages were suggested from the robust methods were then reexamined for linkage using the likelihood (lod score) method. Results from the segregation analyses were consistent with major gene determination of apo B and HDL-C levels, the HDL-C to apo A1 ratio, the LDL-C to apo B ratio, and a measure of relative content of cholesterol in HDL-C and LDL-C. Linkage between haptoglobin and the HDL-C/apo A1 ratio was suggested, with a lod score of 1.72 at theta = 0.05.

Apolipoprotein A-I↗
PubMed1987

Association between polymorphic blood markers and risk factors for cardiovascular disease in a large pedigree.

A large pedigree with high prevalence of heart disease is investigated to analyse the association between polymorphic blood markers and quantitative risk factors for cardiovascular disease. The analysis incorporates a familial correlation structure among the individuals in the pedigree and a generalized power transformation to induce approximate residual normality of the risk factors. A total of 380 marker/risk factor combinations are analysed, and at the normal 1% significance level, positive associations are found between the A antigen of the ABO locus and both serum total cholesterol and low-density lipoprotein cholesterol, and negative associations are found between the B antigen of the ABO locus and serum total cholesterol, and between the B allele of acid phosphatase (AP) locus and systolic blood pressure.

ABO Blood-Group System↗
PubMed1987

Linkage studies of Friedreich ataxia by means of blood-group and protein markers.

Friedreich ataxia (FA) is an autosomal recessive, neuro-degenerative disorder in which the pathogenetic mechanism remains unidentified despite extensive biochemical studies. Genetic-linkage studies provide an alternative approach to determining the basic defect. Linkage analysis between FA and 36 polymorphic-blood-group and protein markers has been carried out on three separate patient populations--16 families from the inbred Acadian population of Louisiana, 21 French-Canadian families from Quebec, and nine apparently unrelated British families--in an attempt to determine the chromosomal location of the disease mutation. Neither evidence of linkage to any of the markers investigated nor heterogeneity among the populations was found for any of the comparisons. The negative lod scores exclude the locus for FA from greater than 20% of the genome.

Blood Group Antigens↗
PubMed1985

PGM1 null allele detected in a Caucasian mother-son pair.

The presence of a PGM1 null allele in a mother and her son was deduced from their inconsistent phenotypes. Quantitation studies were done to confirm the half-normal enzyme activity. Phenotype analysis of 29 additional genetic markers gave no indication of non-parentage, making non-maternity a very unlikely explanation for the discrepancy.

Alleles↗
PubMedDate not supplied

Isolation and characterization of a Rhizobium loti gene required for effective nodulation of Lotus pedunculatus.

A Rhizobium loti gene required for effective invasion of the host Lotus pedunculatus has been identified by transposon Tn5 mutagenesis. Cosmids that complemented a previously isolated mutation (239) at this invasion (inv) locus were identified by in planta complementation and used to construct a physical map of the gene region. The insertion site of Tn5 in PN239 was mapped to a 7.5-kb EcoRI fragment, which complemented the mutation when subcloned into pLAFR1. Further Tn5 mutagenesis of the 7.5-kb fragment was carried out in Escherichia coli using bacteriophage lambda 467, and the mutations homogenotized into R. loti NZP2037. Three additional Fix- mutations were isolated, and these were found to map adjacent to the position of the original mutation in strain PN239. All the other Tn5 insertions isolated in the 7.5-kb fragment gave a Fix+ phenotype on L. pedunculatus. Electron microscopic examination of the L. pedunculatus nodules induced by the isolated Fix- mutants showed that bacteria were either blocked in release from the infection threads or were unable to undergo normal bacteroid development. The inv locus as defined by the Tn5 insertions was sequenced, and a single open-reading frame (ORF) of 576 bp, corresponding to a polypeptide of 21.3 kDa, was identified. The position and orientation of this ORF were consistent with those of the isolated Tn5 Fix- insertions.

Amino Acid Sequence↗