Biomedical subjects

D G Wiesch

Publications and source records attributed to D G Wiesch.

5 recordsLinked to original sources

PubMed2000

Strategies for analyzing genotype-phenotype relationships in asthma.

Asthma is a genetically complex disease with a multifaceted phenotype. Different approaches including population-based and family-based methods for evaluating genotype-phenotype relationships in asthma are discussed as well as the problems that may obscure these determinations. Examples of similar efforts in cystic fibrosis and breast cancer are considered in addition to interaction between causative genes and etiologically relevant environmental exposure.

Asthma↗

PubMed1999

Evaluation of replication studies, combined data analysis, and analytical methods in complex diseases.

Due to genetic heterogeneity, phenocopies, incomplete penetrance, misdiagnosis, and unknown mode of inheritance, linkage studies of most complex diseases are unlikely to provide conclusive findings with unambiguously high lod scores. Typically, several marginally significant lod scores or elevated lod scores are observed in a genome-wide screen. However, it is usually difficult to differentiate these findings from false positives (type I errors). Two approaches are commonly used to guard against false positives: replication studies in independent samples and combined data analysis. In the current paper, we evaluated these two common approaches using simulated data where data from multiple groups were available and locations of disease genes were known. We found replication studies and combined data analysis performed similarly in terms of their ability to identify true and false positive linkages. Both approaches confirmed two true linkages and did not confirm any false positive linkages. The results also indicated that it is not appropriate to apply the criteria proposed for confirming significant evidence for linkage to confirm regions with only suggestive evidence for linkage. The current results support previous findings that parametric analysis using an incorrect genetic model can still identify a true linkage.

Environment↗

PubMed1999

Genetics of asthma.

Asthma is a complex disease with a phenotype that has been clinically difficult to define. Associated phenotypes including bronchial hyperresponsiveness and atopy have provided useful objective alternatives in genetic and epidemiologic studies. Although asthma genes have not yet been identified, much progress has been made toward this goal. Genetic studies indicate that multiple genes are involved in the pathogenesis of this disease, and chromosomal regions likely to harbor asthma susceptibility genes have been replicated in several studies. Environmental factors, including smoking, diet, and viral respiratory infections, have also been implicated in the etiology of asthma. Directly linking these exposures as causes of asthma, however, has also proved difficult. Furthermore, interaction between susceptibility genes and environmental factors is probable and is a challenge currently being pursued by investigators worldwide. Understanding the fundamental gene-environmental interactions in the development of asthma should lead to earlier identification of susceptible individuals and more effective approaches for disease prevention.

Asthma↗

PubMed1999

Genetics of allergy and bronchial hyperresponsiveness.

Allergy and asthma are closely related complex diseases caused by a combination of both genetic and environmental influences. Two common genetic approaches, candidate gene studies and genome-wide screens, have been used to localize and evaluate potential genetic factors that confer susceptibility or modify the phenotype of these diseases. Four genome screens suggest multiple chromosomal locations likely to contain asthma and allergy genes and many potential candidate genes exist in these regions. These screens were performed in six different populations and identified many common susceptibility regions as well as novel regions for each population. Ideally, these genes may point towards key biological pathways that will eventually serve as targets for therapeutic agents.

Asthma↗

PubMed1998

Genetics of complex human diseases: genome screening, association studies and fine mapping.

Positional cloning has been applied successfully to many Mendelian disorders. Because of the public health significance, there is strong interest in mapping susceptibility genes for common disorders, such as asthma and allergy, that have a genetic component. Genome-wide screening has been very useful in detecting regions of the genome likely to contain susceptibility genes. There are multiple chromosomal regions implicated in asthma and now the difficult process of finding the genes and relevant mutations is underway. Two approaches that are being utilized are those of association studies in candidate genes, and haplotype sharing or identical by descent (IBD) mapping. Although these are useful approaches, it is important to realize the strengths and limitations of each. The level of significance needed for an initial study or a replication study should be considered in light of the prior evidence for studying a specific gene polymorphism. Haplotype-sharing approaches, although difficult to use in outbred heterogeneous populations, may provide important insight into fine mapping and gene localization.

Asthma↗