PubMed · 11630833
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P Frascani. 1980. [Not Available].. https://pubmed.ncbi.nlm.nih.gov/11630833/
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BACKGROUND: Effective gene mapping based on genetic association data will require detailed knowledge of patterns of linkage disequilibrium (LD) in human populations. It has been recently suggested that linkage disequilibrium in humans may be organized in a block-like structure, with islands of high LD separated by regions of rapid breakdown of LD due to recombination hotspots. The experimental data to date, however, are limited, and fundamental questions remain about the implications of recombination rate heterogeneity. Here, we use computer simulations to evaluate how such heterogeneity influences patterns of LD, and we develop formal criteria to assess whether the patterns are functionally block like in the context of association mapping. RESULTS: Our analyses suggest that, even in models of extreme recombination rate heterogeneity, some human populations will have a functionally block-like structure to the pattern of LD, but others will not, depending on their precise demographic histories. In fact, for many models, we find that, following an LD-generating event, populations may move through discrete phases that can be functionally described as pre-block, block, and post-block. An analysis of observed and expected patterns of LD surrounding hotspots within the MHC Class II region confirms these theoretical expectations. CONCLUSIONS: Even if highly punctuated patterns of recombination are the rule, patterns of LD are still likely to show differences among populations and among genomic regions that are of practical importance in the design of genetic association studies. The notion that the average extent of LD is a useful concept for the design of association studies must be abandoned in light of the experimental and theoretical evidence.
The authors examine the research evidence on the effect of residential segregation on health, identify research gaps, and propose new research directions. Four recommendations are made on the basis of a review of the sociological and social epidemiology literature on residential segregation: (1) develop multilevel research designs to examine the effects of individual, neighborhood, and metropolitan-area factors on health outcomes; (2) continue examining the health effects of residential segregation among African Americans but also initiate studies examining segregation among Hispanics and Asians; (3) consider racial/ethnic segregation along with income segregation and other metropolitan area factors such as poverty concentration and metropolitan governance fragmentation; and (4) develop better conceptual frameworks of the pathways that may link various segregation dimensions to specific health outcomes.
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