MLIP: using multiple processors to compute the posterior probability of linkage

<p>Abstract</p> <p>Background</p> <p>Localization of complex traits by genetic linkage analysis may involve exploration of a vast multidimensional parameter space. The posterior probability of linkage (PPL), a class of statistics for complex trait genetic mapping in humans, is designed to model the trait model complexity represented by the multidimensional parameter space in a mathematically rigorous fashion. However, the method requires the evaluation of integrals with no functional form, making it difficult to compute, and thus further test, develop and apply. This paper describes MLIP, a multiprocessor two-point genetic linkage analysis system that supports statistical calculations, such as the PPL, based on the full parameter space implicit in the linkage likelihood.</p> <p>Results</p> <p>The fundamental question we address here is whether the use of additional processors effectively reduces total computation time for a PPL calculation. We use a variety of data – both simulated and real – to explore the question "how close can we get?" to linear speedup. Empirical results of our study show that MLIP does significantly speed up two-point log-likelihood ratio calculations over a grid space of model parameters.</p> <p>Conclusion</p> <p>Observed performance of the program is dependent on characteristics of the data including granularity of the parameter grid space being explored and pedigree size and structure. While work continues to further optimize performance, the current version of the program can already be used to efficiently compute the PPL. Thanks to MLIP, full multidimensional genome scans are now routinely being completed at our centers with runtimes on the order of days, not months or years.</p

Genetic admixture, inbreeding and heritability estimates in captive African cheetahs (Acinonyx jubatus) including linkage analysis for the King cheetah phenotype

This multifaceted study primarily aimed at understanding the genetic make-up of captive versus wild cheetah (Acinonyx jubatus) populations in South Africa, with a specific emphasis on a valuable gene pool of a recessive phenotype that is increasingly being maintained in captive population country-wide. The current literature on cheetah genetics has very little information on diversity levels of wild South African cheetahs, and no information on founder dynamics and genetic make-up of South African captive populations. Decisions on cheetah relocations are being made, implementing current conservation policy, from assumptions on origin and relatedness. This research compared population genetic parameters within the largest South African captive cheetah population to free-ranging Namibian and South African conspecifics. The study addressed concerns regarding excessive Namibian genetic introgression into the native captive population and established the extent of genetic variability and Namibian ancestry within the captive population. The study has attempted to address the rising concern among conservation officials with respect to illegal trade of wild-captured cheetahs, wild caught cheetahs that are sold as captive-bred after implanting a microchip. In addition to establishing routine parentage verification using genetic markers that are polymorphic in this species, this study established a technique powerful enough to estimate ancestry in cheetahs of unknown antecedents. The potential of spatial Bayesian clustering to differentiate the point of origin of unknown cheetahs was exploited and in addition, a database for future forensic efforts to address the problem of illegal trade was established. The captive population that was part of this dataset proved to be quite admixed, excepting for the King lineage which was distinct. The second aspect of this study investigated complex conditions such as development of gastritis, renal conditions and/or susceptibility to infections and its relation to pedigree and marker based inbreeding levels. Heritability values for important breeding traits were estimated from pedigree records of 532 cheetahs and are reported for the first time. Gastritis was weakly correlated to the expression of the King trait. Finally, a smaller cohort of the captive pedigree that segregates for a recessive colour variant called the King phenotype was tested for the assumption that the variation is a mutation of the tabby locus described in domestic cats. Genetic linkage analysis was done by testing microsatellite markers detected linked to Tabby for linkage to a conserved region in the cheetah that potentially codes for the King coat colour. Genetic linkage analysis was not detected between the King locus and the domestic cat microsatellite markers used for this study, with LOD scores remaining non-significant for all the markers.Thesis (PhD)--University of Pretoria, 2011.Production Animal Studiesunrestricte