Blunt snout bream (Megalobrama amblycephala) were infected with Aeromonas hydrophila to distinguish susceptible and disease resistant individuals.PCR and DNA sequencing were used to screen single nucleotide polymorphisms (SNP) in the MHCⅡ a gene of blunt snout bream.High-resolution melting and restriction enzyme digestion were used to analyze the relationship between gene polymorphism and disease resistance with SNP genotyping.A total of 35 SNP sites (1.45% of total nucleotide) out of the MHCⅡ a gene were screened,including 30 transition sites and 5 transition sites.Among these 35 SNPs,1 was found to be located in the 5′-untranslated region (UTR),16 located in exon,7 located in intron,and 11 located in 3′ UTR.Coding sequence region contained 13 SNPs (5.56% of total amino acid).Among them,TA transversion located at 839 bp and AG transition located at 1 663 bp were nonsense mutations,and the other 11 SNPs were sense mutations.The percentage of SNPs of nucleotide and coding region in α1 domains were 4.88% and 10.98%,respectively,significantly higher than that in α2 domain (1.08% and 3.22%).There were 4 variable sites in the 21 peptide binding region (PBR),with the mutation rate of 19.05%.However,the mutation rate of nonPBR was just 8.20% (5/61).The genotype and allele frequencies of the 5 successfully genotyped SNP sites in the 100 bacterial septicemia susceptible and 100 resistant individuals were statistically different.Result of Chisquare tests showed that the differences of genotype and allele frequencies of SNP (T/A) located at 1 395 bp were extremely significant (P＜0.01),SNPs located in 221 bp (G/T) and 1 859 bp (G/T) were significant different between susceptible and resistant groups (P＜0.05).It is indicated that the MHCⅡ a gene polymorphism is significant correlated with bacterial septicemia resistance.