SNP Polymorphism Of SHANK3 And GRIK5 Genes In Domestic Dogs And Grey Wolves

The progress of human civilization brings opportunities for domestication of domestic animals,especially domestic dogs,which are close to human beings.Under the influence of'strong artificial selection,domestic dogs and progenitor in grey wolves show great differences in morphology,behavior and temperament.Besides,more than 400 breeds with different shapes and temperaments formed during last 200 years.All of them reflected in the geno,me.Based on genome-wide single nucleotide polymorphism(SNP)arrays,previous studies found the pattern of population genetics of dogs changed in the process of domestication.Fragment of Linkage Disequilibrium(LD)got longer,genetic diversity reduced,harmful mutations increased,and incidence of genetic diseases was significantly higher in some breeds.As time passed,allele frequencies of different populations of dogs diverted.Domestic dogs and humans share the same living environ,ment and show the phenomenon of convergent evolution in many aspects,which has been used as a research model to study diseases,neurodevelopment and mental diseases of humans.Dogs are more similar to humans in nervous system than other model animals like mouse and zebra fish.When dogs were tested in diseases studies,they act similarly as humans.Moreover,dogs could communicate and feedback to humans well.In this study,single SNP polymorphism of SHAANK3 and GRIK5 genes with the highest FST value between dogs and wolves was studied.Two genes SHANK3 and GRIK5 have been revealed to related to mental illness of humans.SHANK3 can form scaffolds by interacting with various proteins in cell membrane and cytoplasm through its own different domains.GRIK5 plays an excitatory neurotransmitter role in L-glutamate in many synapses of the central nervous system.The five SNPs with the highest FST value in genes SHANK3 and GRIK5 were four sites of SHANKS gene,Chr10:16622120,Chr10:16624015,Chr10:16625169,and Chr10:16629468,and one site of GR1K5 gene,Chrl:112315095.The annotation results showed that all five sites were located in the intron region.The regulatory element prediction showed that they were all related to neurogenesis,expression and migration of nerve cells,and regulation factors of differentiation.Through DNA sequencing and analysis,it was found that the SNP genotype frequency of gray wolves at these five loci was polymorphic,while that of domestic dogs was nearly fixed.The SNP genotype frequencies were significantly different between wolves and dogs(P<0.01).The heterozygous rate of the five sites of domestic dogs was 0-0.095.and that of gray wolves was 0.09-0.283.The difference in genetic diversity suggested that these two genes were positive selected in the domestication process of domestic dogs from gray wolves.The results of SNP genotype frequency of differ populations in wolves showed that there was a significant difference between the European and the other four group wolves at Chrl:112315095 and there were also significant differences between North America,Yun-Gui-Chuan and north Asia group.There was a significant difference between the Middle East and the European and north Asian wolves,and between the Middle East wolves at Chr10:16622120,Chr10:16624015 and Chr10:16625169.There were significant differences between wolf populations of north Asian and Yun-Gui-Chuan,north American and middle eastern,between north American and Yun-Gui-Chuan,and between European and middle eastern at Chr10:16629468.There was no significant difference in the four loci of SHANK3 gene between native dogs,docile breeds and aggressive breeds.In GR1K5 gene Chrl:112315095 loci,SNP genotype frequency of aggressive breeds was significantly different to that of native dogs and docile breeds.It suggested that fixed process of A-G was affected by domestication of domestic dogs.The G genotype may make domestic dogs more docile,and be better close to people.The genotype A,which is high in the aggressive breeds,may be associated with aggressive behavior.This study could be improved in these proceeding:1.more sa,mple could avoid bias;2.comparison with extreme samples of domestic dogs could identify the polymorphism in disposition inside dogs;3.all SNPs of the whole candidate genes could provide information about haploid and LD,which could define the selected sites and genotype about mental state.Research of the function of the two genes in domestic dogs and wolves on the mental state could further explore the mental status of domestic dogs and relative diseases of humans.It is expected that dogs might be designed as model animals,provide insights for the treatment of diseases and drug research.