Related Experiment Videos
A second-generation genomewide screen for asthma-susceptibility alleles in a founder population
1Department of Human Genetics, The University of Chicago, Chicago, IL, 60637, USA. carole@genetics.uchicago.edu
American Journal of Human Genetics
|October 7, 2000
Summary
This study identified 23 new genetic loci linked to asthma and atopy susceptibility in Hutterites, significantly advancing our understanding of these complex conditions. These findings highlight potential common genetic factors influencing asthma and atopy across diverse populations.
Area of Science:
- Genetics
- Immunology
- Epidemiology
Background:
- Asthma and atopy are complex diseases with significant genetic components.
- Previous genome screens in Hutterites identified preliminary susceptibility loci.
Purpose of the Study:
- To conduct a genomewide screen for asthma and atopy susceptibility loci using an expanded Hutterite pedigree.
- To increase statistical power for identifying and confirming genetic linkages.
Main Methods:
- Utilized 563 markers across a 15-generation Hutterite pedigree (693 individuals).
- Employed likelihood ratio (LR) chi(2) test for linkage and transmission/disequilibrium (TDT) test for association.
- Investigated 17 candidate genes for association with asthma and atopy.
Main Results:
- Identified 23 loci in 18 chromosomal regions with 10-fold increased significance (P<.001) compared to prior studies.
- Newly identified linkages in 11 regions, including five (5p, 5q, 8p, 14q, 16q) showing both linkage and disequilibrium.
- Found associations with IL4RA, HLA class II, and interferon-alpha genes, but these regions lacked strong linkage evidence.
- Confirmed linkage on chromosome 19 and identified a CD14 polymorphism in linkage disequilibrium with an unknown susceptibility allele on 5q.
Conclusions:
- The expanded Hutterite cohort significantly enhanced the power to detect asthma and atopy susceptibility loci.
- Multiple chromosomal regions show strong evidence for linkage and/or association, implicating novel genetic factors.
- Findings suggest that 10 identified regions may harbor common alleles with substantial effects on asthma and atopy in various populations, warranting further investigation.