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Abstract Populations of buffaloes with one milk record for each buffalo were generated using Monte Carlo simulation procedure of SAS (2004) with assumed mean (0) and variance (1). Four different sizes of populations (z): 10000, 25000, 50000 and 100000 animals were obtained. Four generations of progeny were obtained by selection of sires and dams of the next generations. Mating ratio (male: females) were designed to differ from 1:25 to 1:100 in natural mating (NM) and from 1:1000 to 1:5000 in artificial insemination (AI). The objective of using different mating ratios was to compare between different selection intensities among males. Genetic gain per generation and annual genetic gain were calculated. Genetic gain increased significantly (P<0.05) with the increase in generation number (G) being 282, 389, 457 and 488 kg milk for G1, G2, G3 and G4, respectively. The annual genetic gain (G/Y) ranged from 48 kg/yr for G1 to 83 kg/yr for G4. The annual genetic gain ranged from 64 kg/yr for z=10000 to 73 kg/yr for z=100000. Increasing nucleus size (p) from 0.05 to 0.10 increased genetic gain significantly (P<0.05) from 390 to 418 kg milk. Non-significant differences in genetic gain among different proportions of males born used as sires (a) were observed. The main variables affecting the fraction of base sires born in nucleus (w) were z, p and a. Annual genetic gain ranged from 50 to 66 kg milk/yr in NM and from 80 to 82 kg milk/yr in AI. Applying open nucleus breeding scheme for multiple generations of selection could accelerate the rate of genetic gain of milk production in Egyptian buffalo and increased the average milk yield from 15% in G1 to 26% in G4. Inbreeding coefficient increased significantly (P<0.05) with the increase in generation number (G) in both the nucleus and the base populations. Significant increase in inbreeding coefficient (P<0.05) were observed between mating ratios (MR) in natural mating (NM) and artificial insemination (AI) in both the nucleus and the base populations |