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The population structure and genetic diversities of Clarias gariepinus from the cultured population at Chi Farm (Ajanla) and wild population at Asejire Reservoir (Asejire) were analysed using Random Amplified Polymorphic DNA (RAPD) and Microsatellite DNA markers. Using a CTAB protocol, genomic DNA was extracted from the caudal fins of 20 samples of live specimen collected from each population. Seven RAPD primers and seven pairs of microsatellite DNA primers were used to amplify different loci on the extracted genomic DNA by Polymerase Chain Reaction and the resultant DNA fragments were analysed on agarose gel. The RAPD primers amplified a total of 474 loci with 697 bands in all samples for the seven primers studied. The cultured population from Chi farm showed a total of 366 bands, while the wild population from Asejire Reservoir displayed 331 bands. The cultured population showed a negative inbreeding coefficient (F) of -0.173 ± 0.209, which statistically suggests excess heterozygosity, while a positive but low inbreeding coefficient of 0.042 ± 0.243 was estimated for the wild population. The Analysis of Molecular Variance (AMOVA) for both genetic markers indicated significant difference (p=0.01) between the two populations. The result of the study suggests a loss or on-going loss of genetic variability, which needs conservation intervention in the two populations studied.