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Linkage disequilibrium in growing and stable populations
1Department of Integrative Biology, University of California, Berkeley 94720.
Genetics
|May 1, 1994
Summary
Fisher's exact test can detect allele associations. Rapid population growth significantly reduces the chance of finding these associations, even in linked genes, as seen in human mitochondrial DNA data.
Area of Science:
- Population Genetics
- Molecular Evolution
- Bioinformatics
Background:
- Nonrandom associations between alleles at different loci, known as linkage disequilibrium, are crucial in population genetics.
- Fisher's exact test is a statistical method used to assess the significance of these associations.
- Understanding factors influencing linkage disequilibrium is key to interpreting genetic variation.
Purpose of the Study:
- To investigate the impact of population growth on the detection of linkage disequilibrium.
- To evaluate the probability of observing significant nonrandom associations between linked neutral loci under different population size scenarios.
- To analyze human mitochondrial DNA sequence data to illustrate the effect of rapid population growth on linkage disequilibrium.
Main Methods:
- Extensive computer simulations were conducted to model linkage disequilibrium in populations of constant and growing sizes.
- Fisher's exact test was applied to simulated data and real human mitochondrial DNA sequence data.
- Analysis involved comparing allele associations at polymorphic neutral loci and informative sites in DNA sequences.
Main Results:
- Simulations revealed a substantial probability of significant nonrandom associations in constant-sized populations at equilibrium.
- Rapid population growth significantly reduces the likelihood of detecting significant linkage disequilibrium, even for completely linked loci.
- Analysis of human mitochondrial DNA showed lower disequilibrium in Sardinians (rapid growth) compared to !Kung and Pygmies (slower growth).
Conclusions:
- Rapid population expansion can obscure or eliminate detectable linkage disequilibrium signals.
- Gene genealogies, particularly "star-like" patterns associated with rapid growth, are inversely related to the extent of linkage disequilibrium.
- The findings have implications for inferring population history and genetic structure from molecular data.
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