Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.

We use a calculation of periodic homogeneous isotropic turbulence to simulate the experimental decay of grid turbulence. The calculation is found to match the experiment in a number of important aspects and the computed flow field is then treated as a realization of a physical turbulent flow. From this flow, we compute the large eddy field and the various averages of the subgrid-scale turbulence that occur in the large eddy simulation equations. These quantities are compared with the predictions of the models that are usually applied in large eddy simulation. The results show that the terms which involve the large-scale field are accurately modelled but the subgridscale Reynolds stresses are only moderately well modelled. It is also possible to use the method to predict the constants of the models without reference to experiment. Attempts to find improved models have not met with success.