Biomedical subjects

S E Poduslo

Publications and source records attributed to S E Poduslo.

At least 19 recordsLinked to original sources

PubMed2002

Lack of association of the two polymorphisms in alpha-2 macroglobulin with Alzheimer disease.

Alzheimer disease is a complex neurodegenerative disorder that is characterized by cognitive decline and distinct neuropathology. The gene for alpha-2 macroglobulin (A2M) on chromosome 12 has two polymorphisms that, in some cases, are associated with Alzheimer disease. We examined these two polymorphisms in our families in the DNA Bank (a collection of DNA samples from families with Alzheimer disease in Texas). Using both association studies and sib transmission/disequilibrium tests, we found no association of the two polymorphisms with the disease in our collection. In addition, we did not find an association of the disease with the two polymorphisms in A2M in a small subset of National Institute of Mental Health (NIMH) families. Thus, our studies do not support the A2M polymorphisms as a risk factor for Alzheimer disease.

Adult↗

PubMed2001

A new locus on chromosome 19 linked with late-onset Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder, characterized by cognitive decline and distinctive neuropathology. APOE 4 and APOCI A on chromosome 19 are risk factors for late-onset disease. Using large extended families with multiple siblings affected, we have identified several microsatellite markers which are also linked with late- onset Alzheimer's disease. These microsatellites are distal from the apolipoprotein cluster on chromosome 19. It is likely that multiple genes will be involved with late-onset disease, either as risk factors or as causative agents.

Age of Onset↗

PubMed2001

Chromosome 12 and late-onset Alzheimer's disease.

Alzheimer's disease is a complex neurodegenerative disorder, characterized by cognitive decline and distinctive neuropathology. Using large extended families with multiple affected, we found that three markers on chromosome 12 were linked with late-onset Alzheimer's disease. These markers were downstream from the gene for alpha-2 macroglobulin. It is likely that multiple genes will be identified either as risk factors or as causative agents for late-onset Alzheimer's disease.

Age of Onset↗

PubMed2001

High-performance implementation and analysis of the Linkmap program.

Linkage analysis uses information from family pedigrees to map genes and locate disease genes on particular chromosomes. A recombination fraction denoted as theta is estimated as a measure of crossing over between two loci. Genetic linkage calculations are very time-consuming particularly for large family pedigrees, a large number of theta values, and an increased number of markers. This paper reports the implementation of a dynamic master-slave scheme for the parallelization of the Linkmap program on a high-performance cluster such as the Origin 2000 (O2K) consisting of 56 R12000 processors. The Linkmap program is one of four programs in the LINKAGE/FASTLINK legacy package widely used by the medical research community. Implementations issues are addressed and results are compared with previous results on a cluster of DEC Alphas, and with the sequential execution on the O2K machine.

Chromosome Mapping↗

PubMed2001

Dementia: the University of Oklahoma autopsy experience.

The brain from 98 consecutive patients with the clinical diagnosis of dementia were examined at autopsy in a standardized fashion. Alzheimer's Disease was present in 79 of the cases, 76%, but represented the only diagnosis in 41%. Thus, almost 60% had another associated pathologic disorder. Cerebral amyloid angiopathy (CAA) represented the single largest subset, present in 25 cases. 40% were accompanied by either 1) small, microscopic infarcts or cortical scars, or 2) small collections of macrophages containing hemosiderin or small hemorrhages. CAA occurred with both atherosclerotic cortical infarcts and arteriolosclerotic subcortical pallor or lacunar infarcts. Alzheimer's Disease occurred with Diffuse Lewy Body (DLB) Disease in 13 cases. DLB Disease did not occur as a distinct entity, and thus may represent the second largest subset of Alzheimer's Disease. Both Alzheimer's Disease and DLB Disease accounted for dementia in Parkinson's Disease. Almost 25% of all cases had a disorder other than Alzheimer's Disease.

Alzheimer Disease↗

PubMed2000

The cardiac sodium channel mRNA is expressed in the developing and adult rat and human brain.

Expression of the rat (RH-I/SkM2) and human (hH1/SCN5A) tetrodotoxin-resistant (TTX-R), voltage-sensitive sodium channels is thought to be specific to cardiac tissue. We detected RH-I/SkM2 mRNA in newborn rat brain using both RNase protection assay analysis and in situ hybridization and in adult rat brain using RNase protection assay analysis. This expression was observed primarily in developing limbic structures of the cerebrum and diencephalon, and in the medulla of the brain stem. Using RT-PCR analysis, we detected hH1/SCN5A mRNA in both fetal and adult human brain. Interestingly, mutations in the human cardiac sodium channel are known to lead to cardiac abnormalities, which result in arrhythmias and frequently in sudden cardiac death. If these mutant channels were also expressed in limbic regions of the brain, alterations in channel function could have drastic effects on the brain's signaling ability, possibly promoting seizure activity.

Adult↗

PubMed2000

On the parallelization of linkmap from the LINKAGE/FASTLINK package.

Genetic linkage calculations can be time consuming, even on a fast computer. The ability to collect large family pedigrees has increased the magnitude of linkage computations. Sequential genetic algorithms have many successful applications in very different domains, but they have a main drawback in their utilization. Evaluations are very time-consuming, e.g., a pedigree consisting of 55 nodes takes about 70 min on a DEC-Alpha processor and about 270 min on a 166 MHz Pentium for certain likelihood calculations. This time increases exponentially with the increase in the size of the pedigree. In order to solve these shortcomings and to study new models of higher efficiency and efficacy, parallel platforms are being used for genetic programs. LINKAGE is a software package for performing genetic likelihood calculations; FASTLINK is an improved, faster version of it. This paper provides a parallel implementation of the "Linkmap" program (one of the four programs in LINKAGE/FASTLINK) for a heterogeneous environment, using a static and a dynamic strategy for task allocation. It was found that the increased performance by the dynamic strategy was close to the estimated maximum speed up.

Algorithms↗

PubMed1998

The apolipoprotein CI A allele as a risk factor for Alzheimer's disease.

The E4 allele for the apolipoprotein E gene has been shown to be a significant risk factor for Alzheimer's disease. The gene is located in a conserved gene cluster on chromosome 19q12-13.2. Downstream from APOE is the gene for apolipoprotein CI. We had previously shown that the presence of a restriction site in the 5'end of APOCI (the A allele) was present at increased frequency in Alzheimer's patients and could also be considered as a risk factor for the disease. We have extended these studies and find that both familial and sporadic cases of Alzheimer's disease have a higher frequency of the APOCI A allele than control spouses. In addition, male patients with the APOCI A allele and/or the APOE4 allele tend to have an earlier age of onset of the disease than female patients.

Age of Onset↗

PubMed1996

A presenilin 1 mutation in an early onset Alzheimer's family: no association with presenilin 2.

Genes on four chromosomes have been associated with Alzheimer's disease. Mutations in the chromosome 14 gene (S182 or presenilin 1) have been linked with an aggressive very early form of the disease while mutations in a chromosome 1 gene (STM2 or presenilin 2) have been linked with Volga German kindreds. When we screened our Alzheimer's patients for the first mutations reported, we only found one in the presenilin 1 gene in an extended family with three affected siblings, all of whom had onset of symptoms in their 4Cs. ApoE and ApoCI genotyping indicated that these risk factors were not associated with the disease in this family. None of our patients with early or late onset disease had the mutation described for presenilin 2.

Age of Onset↗

PubMed1995

A closely linked gene to apolipoprotein E may serve as an additional risk factor for Alzheimer's disease.

The E4 allele of the apolipoprotein E (APOE) gene has been identified as a risk factor for Alzheimer's disease. Immediately downstream from the APOE gene on chromosome 19 is the gene for apolipoprotein CI (APOCI). We have found that the frequency of an APOCI restriction site is 0.45 for Alzheimer's patients and 0.14 for control spouses, which is similar to the frequencies for the APOE4 allele. The APOE4 allele is in linkage disequilibrium with the APOCI restriction site. Thus both the APOE4 allele and the APOCI restriction site may be considered as risk factors for Alzheimer's disease.

Aged↗

PubMed1995

Apolipoprotein E and B alleles in Parkinson's patients.

Parkinson's patients were genotyped for the apolipoprotein E alleles as well as polymorphisms at the apolipoprotein B loci to determine whether they were at risk for late onset Alzheimer's disease or coronary disease. The Parkinson's patients were at no greater risk for either disease than were the control spouses. The frequency for the APOE4 allele was 11% compared with the spouses, 10%. Interestingly, 20% of the patients had the 2/3 genotype which may have a protective effect from late onset Alzheimer's disease.

Aged↗

PubMed1995

Association of apolipoprotein E but not B with Alzheimer's disease.

In our studies apolipoprotein E4 (APOE4) is associated with both early- and late-onset Alzheimer's disease. Alzheimer's patients from West Texas were screened for the APOE4 allele, which was found at frequencies of 0.43 and 0.59 in familial late- and early-onset cases. Sporadic cases had lower frequencies, but they still were 2-4 times higher than control spouses. To determine whether the APOE association may be a risk factor for coronary disease as well, we examined two APOB gene restriction sites that have previously been found to be associated with coronary artery disease, especially myocardial infarctions. The APOB alleles were found at similar frequencies in Alzheimer's patients and control spouses.

Aged↗

PubMed1995

A new polymorphism in the gene for the dopamine D2 receptor.

A new polymorphism has been identified in the gene for the dopamine D2 receptor. The polymorphism was found by single-stranded conformational polymorphism (SSCP) analysis. Sequencing revealed an insertion at a BsoF1 restriction site. This polymorphism in the 3'-untranslated region was found at a frequency of 0.07 in Centre d'Etude du Polymorphisme Humain (CEPH) parents.

Base Sequence↗

PubMed1993

Association of a monoamine oxidase B allele with Parkinson's disease.

Monoamine oxidase B (MAO-B) is implicated in the cause of Parkinson's disease (PD) because of its role in metabolizing the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and forming H2O2 during dopamine metabolism. Altered MAO-B activity has been observed in PD platelets. Polymerase chain reaction was used to amplify a portion of the MAO-B gene. Polymerase chain reaction products were screened with restriction enzymes to identify fragments useful for single-stranded conformational polymorphism analysis. A single-stranded conformational polymorphism was identified in an MAO-B polymerase chain reaction product after Hae III digestion. One hundred twenty-one control individuals were allelotyped with frequencies of 0.45 and 0.55 for alleles 1 and 2, respectively. Frequencies of 0.62 and 0.38 (1 and 2, respectively) were observed in a population of 46 patients with PD. The presence of MAO-B allele 1 is associated with a relative risk for PD of 2.03-fold (confidence interval, 1.44-2.61; p < 0.02). For comparison, a monoamine oxidase A polymorphism was used to determine allelic frequencies in these same populations and no statistically significant differences were found. These results suggest that an inherited variant of MAO-B may be involved in a genetic predisposition for PD.

Aged↗

PubMed1993

A new polymorphism in the gene for GAP43.

A new polymorphism has been identified in the 3'-untranslated region of the gene for GAP43. It is present with a frequency of 0.327 in the Centre d'Etude du Polymorphisme Humaine (CEPH) parents and is slightly lower in Alzheimer's (0.269) and Parkinson's (0.231) patients.

Alzheimer Disease↗

PubMed1993

Identification of a new polymorphism in the human proteolipid protein gene.

A polymorphism in the gene for proteolipid protein has been identified, using amplification by the polymerase chain reaction, restriction enzyme digestion, and fragment separation by polyacrylamide gel electrophoresis. The polymorphism is located in the transcribed 3'-untranslated region, a region with potential regulatory signals. The mutation consists of a single base pair insertion into a Hae III restriction site, producing a larger rare fragment of 409 bp as compared with the more frequent 325 bp fragment. The gene for proteolipid protein is on the X chromosome; thus the males are hemizygous for the rare allele and the females are heterozygous carriers. The polymorphism occurs with a frequency of 0.046 in a population of European origin and also has a rare frequency in multiple sclerosis patients.

Animals↗

PubMed1991

Detecting high-resolution polymorphisms in human coding loci by combining PCR and single-strand conformation polymorphism (SSCP) analysis.

A strategy is described that allows the development of polymorphic genetic markers to be characterized in individual genes. Segments of the 3' untranslated regions are amplified, and polymorphisms are detected by digestion with frequently cutting enzymes and with the detection of single-stranded conformation polymorphisms. This allows these genes, or DNA segments, to be placed on the linkage maps of human chromosomes. Polymorphisms in two genes have been identified using this approach. A HaeIII polymorphism was detected in the KIT proto-oncogene, physically assigned to chromosome 4q11-12. This polymorphism is linked to other chromosome 4p markers and is in linkage disequilibrium with a HindIII polymorphism previously described at this locus. We have also identified in the insulin-like growth factor1 receptor gene (IGF1R) a 2-bp deletion that is present at a frequency of .25 in the Caucasian population. Pedigree analysis with this insertion/deletion polymorphism placed the IGF1R gene at the end of the current linkage map of chromosome 15q, consistent with the physical assignment of 15q2526. Thus, polymorphisms in specific genes can be used to related the physical, genetic, and comparative maps of mammalian genomes and to simplify the testing of candidate genes for human diseases.

DNA, Single-Stranded↗

PubMed1990

Hydrocortisone induction during oligodendroglial differentiation.

Steroid hormones are important for the normal development of brain. The addition of hydrocortisone to oligodendroglia in culture increases the level of mRNA for proteolipid protein, increases the synthesis of cerebrosides, and provides an induction of activities for the ketone body metabolizing enzymes. While proteolipid protein and cerebrosides are major components of myelin membranes, ketone bodies serve as precursors for lipid synthesis during development. Thus, hydrocortisone is important during the differentiation of oligodendroglia and during initial myelin production.

Animals↗