The purpose of the study is to analyze the genotypic structure and population-genetic parameters of the West Siberian meat and Kulunda fine-wool breed of sheep by the CAST, GDF9 and KRT1.2 genes and blood groups. Molecularnogenetic and immunogenetic studies were carried out in the SRIAH (Siberian Research Institute of Animal Husbandry SFSCA RAS) biotechnology laboratory. PCR-RFLP analysis to determine genotypes was performed according to the described and approved methods on a C1000 “BioRad” amplifier; the results were visualized using an E-Box-CX5.TS-20.M gel documentation system. It was found that the frequency of genotypes and alleles of the CAST gene of West Siberian meat and Kulunda fine-wool breeds have no significant differences. In both breeds, CASTMM was predominant, with a frequency of 69.0–75.0%, CASTNN carriers being only 1.6–5.1%. The Kulunda fine-wool breed is characterized by a very high frequency of the GDF9GG genotype 92.7%, which is higher than that of the West Siberian meat sheep by 26.3%. GDF9AA genotype is extremely rare in breeds (0–5%). The GDF9G allele in the compared breeds was found to range from 0.811–0.960 and the GDF9A allele from 0.189–0.040. There are differences in the ratio of genotypes of the KRT1.2 gene in the compared breeds. In the Kulunda fine-wool breed, the vast majority of animals have homozygous genotype KRT1.2MM (95.5%), whereas in the West Siberian meat breed such sheep constitute 32.8%. Consequently, the frequency of the KRT1.2M allele is 0.565–0.978 and the KRT1.2N allele is 0.435–0.022. The genetic balance in the studied genes is not disturbed, χ2 = 0,033–1,025. The index of genetic similarity between breeds, calculated on the basis of the frequencies of genotypes and blood groups is 0.901 ± 0.028 and 0.833 ± 0.024. Population and genetic characteristics are practically identical in the compared breeds, except for gene homozygosity (Ca), which is higher in the Kulunda fine-wool sheep breed by 24.3% for the GDF9 gene and KRT1.2 by 29.1%, compared to the West Siberian meat sheep breed. The number of effective alleles is insignificant (1.04–1.46). The genetic variability (V) by individual genes in the breeds varies from 5.0 to 49.6%. The negative value of the Fis coefficient indicates the absence of inbreeding in sheep the studied breeds.