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Biomedical subjects

K M Weiss

Publications and source records attributed to K M Weiss.

At least 55 records · Page 3Linked to original sources
PubMed1993

Evolutionary models of quantitative disease risk factors.

Numerous mutations are now known that have significant effects on various phenotypes; many of these mutations are of interest because they influence quantitative risk factors for major diseases. Such diversity raises the question of how much genetic heterogeneity we should expect to find in the effects of alleles, that is, the size of the effects, the number of severe alleles, and their frequency in the population. Can evolutionary models suggest a general pattern? In this article we examine what is currently known about several basic aspects of the problem. These include the distribution of quantitative effects of new mutations on a phenotype, the distribution of allelic effects that would be found in a natural population, and the relationship between these effects and Darwinian fitness. We discuss these issues in light of various models that have been proposed and the existing relevant data. Then we consider how these points relate to the distribution of genetic effects on an important human trait, the cholesterol ratio, an important risk factor for coronary heart disease. The complexities of quantitative traits and inadequacies in the available data prevent definitive models that can directly connect the mutational effects, allelic effects, and fitness distributions from being developed, and we consider how sample limitations and the nonequilibrium of human populations caused by our demographic history make rigorous solutions difficult. However, based on what is currently known, we argue that for human quantitative chronic disease risk factors the nearly neutral models of allelic evolution at single loci probably apply reasonably well. In general, and although much is still speculative, the data available for such risk factors are consistent with these expectations and may enable us to predict many aspects of etiologic heterogeneity for human disease.

Adolescent↗
PubMed1993

A new index of abdominal adiposity as an indicator of risk for cardiovascular disease. A cross-population study.

A new index of abdominal adiposity, the conicity index, and the waist-to-hip ratio (WHR) were compared as health indicators in seven European populations and two USA populations. The total sample included 1280 men and 960 women. Abdominal adiposity as detected by these indices is significantly associated with more cardiovascular risk indicators among women than it is among men. Both indices are equivalent as health indicators. However, the conicity index has several advantages over the WHR: (i) it has a theoretical (expected) range; (ii) it includes a built-in adjustment of waist circumference for height and weight, allowing direct comparisons of abdominal adiposity between individuals or even between populations; and (iii) it does not require the hip circumference to assess fat distribution.

Abdomen↗
PubMed1992

Visual information decoding deficits in schizophrenia.

Schizophrenic and control subjects were tested on two-flash fusion (TFF) and visual backward masking (VBM) tasks in a repeated measures design. Each subject was tested in a single session. Both tasks used the same equipment and stimuli. There was no difference between the groups in their ability to detect the presence of two separate stimuli in the TFF task. Schizophrenic subjects did require longer interstimulus intervals (ISI) than control subjects to accurately report one of the two targets in the VBM task. Analysis of individual targets reveals that the VBM deficit is a function of the similarity of the target and mask. The more feature detail discrimination necessary, the longer an ISI is required in VBM. The data are interpreted as supporting the conclusion that since the groups did not differ in their performance of the TFF task, which would also have been affected by a sensory abnormality, the deficit in VBM must be explained by reference to a higher level of information processing. The VBM deficit is a failure to decode the target stimulus, and is not simply a function of abnormalities due to an overactive transient channel system.

Adult↗
PubMed1992

Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations.

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.

Asian People↗
PubMed1992

On the distinctions between diagnosis, description and measurement of schizophrenia.

The distinctions between diagnostic classification of schizophrenia, the description of the characteristics and course of schizophrenia, and measurement of its severity are discussed. There is confusion among these three categories by both researchers and clinicians. The causes for this confusion are discussed, and it is noted that there are few appropriate measures of cognitive function in schizophrenics. It is proposed that the research design used in most schizophrenia research does not lend itself to the development of more informative interval scales. It is proposed that rather than using performance as a dependent measure with a task of fixed level of difficulty, a 'threshold design' should be used, where the environmental factors are varied to produce a given performance level.

Female↗
PubMed1991

Genetic variation of the mitochondrial DNA genome in American Indians is at mutation-drift equilibrium.

Several surveys have found evidence for founder effects in Amerindian mitochondrial DNA because of the existence of rare Asian morphs in high frequencies in some Amerindian populations and the occurrence of several new morphs not seen elsewhere in the world. These reports, however, do not address whether or not the present genetic variation in the mtDNA genome in Amerindians has reached the steady-state distribution predicted by the mutation-drift theory of population genetics. The present work suggests that in three Amerindian populations (Pima, Maya, and Ticuna) a steady state has apparently been reached, and hence the initial founder effect has probably dissipated during the evolution of Amerindians in the New World. This result is consistent with the genetic variation in nuclear genes in similar populations, shown through surveys of protein variation in earlier work and, more recently, in studies of restriction fragment length polymorphisms.

DNA, Mitochondrial↗
PubMed1991

Genetic studies of human apolipoproteins. XVI. APOE polymorphism and cholesterol levels in the Mayans of the Yucatan Peninsula, Mexico.

Structural variation at the APOE locus is a major determinant of interindividual differences in cholesterol levels in populations at large. We have determined APOE structural polymorphism and estimated its impact on total cholesterol in the Mayans of the Yucatan Peninsula from Mexico. A unique pattern of APOE allele frequency distribution was observed, with no example of the APOE*2 allele and a relatively low incidence (9%) of the APOE*4 allele, giving rise to the lowest average heterozygosity at the APOE locus observed to date. The reported elevating affect of the APOE*4 allele on cholesterol has been found to be absent in the Mayans; several possible explanations which may account for the absence of this affect are discussed. In addition to APOE the gene products of five other apolipoprotein loci were screened and low frequency variation, possibly due to European admixture, was observed in two systems (APOH and APOA-IV).

Alleles↗
PubMed1991

DNA polymorphisms of the apolipoprotein AI/CIII/AIV gene cluster influence plasma cholesterol and triglyceride levels in the Mayans of the Yucatán Peninsula, Mexico.

The purpose of this work was to examine the influence of apolipoprotein gene variation on plasma lipid levels in a population of Mayan Indians of the Yucatán Peninsula, Mexico. Four restriction enzymes: XmnI, PstI, SstI, and PvuII, were used to detect restriction fragment length polymorphisms (RFLP) within the region of the apolipoprotein AI/CIII/AIV gene cluster. The frequencies of these polymorphisms in this Mayan population were similar to those reported for other Amerindian populations, but differed widely from those reported for Caucasian populations. The XmnI and SstI RFLPs were informative for association studies in this population, and we analyzed their influence on the quantitative variation of plasma cholesterol and triglycerides. Using a nonparametric analysis of variance, it is shown that the presence of the XmnI restriction site had a significant effect in lowering plasma cholesterol, whereas the presence of the restriction site for SstI had a significant effect in raising plasma triglycerides. Consequently, genetic indicators of both low and high risk for lipid-related diseases, such as atherosclerosis and coronary heart disease, seem to be present within the same gene region in this Mayan population.

Adult↗
PubMed1991

Studies of three Amerindian populations using nuclear DNA polymorphisms.

Three Amerindian populations, two from Rondônia, Brazil (Karitiana and Rondônia Suruí), and one from Campeche, Mexico (Mayan), were typed for up to 30 nuclear restriction fragment length polymorphisms (RFLPs). Heterozygosities, both observed and expected, were compared with those of Europeans. Average heterozygosity is reduced among these Amerindians (relative to that of Europeans) by 7.0% (Mayan) to 27.1% (Karitiana). This amount of heterozygosity in the nuclear DNA is nevertheless high enough that it is unlikely that there was a severe or prolonged bottleneck.

Alleles↗
PubMed1990

Advantages of reconceptualizing schizophrenia in clinical practice.

Weiss (1989) has proposed abandoning symptom-based diagnosis for schizophrenia research. It is proposed that such a system confuses treatment of symptoms with treatment of the underlying process from which it emanates. Furthermore, it proposes that while a symptom-based system is striving for clarity and objectivity, it is conceptually barren and, thus, offers no treatment framework. A proposed, heuristic model by which to conceptualize major psychiatric disorders is discussed. It is argued that it would have clinical advantages of greater patient acceptance, less social stigma, provide a treatment agenda, allow objective measurement of deficits along a continuum, be more comprehensible by both patient and family, and be more relevant to daily living.

Antipsychotic Agents↗