Study On The Genetic Polymorphisms Of Wild Mice (Mus Musculus) In China

Mouse genetics has currently evolved into a new historical stage, to perform genetic dissection of complex traits, which requires a genetic polymorphism as much as possible. Recent studies revealed that wild mice (Mus musculus) in natural populations harbor far more extensive genetic polymorphisms and less extensive linkage disequilibrium than the laboratory counterparts. An earlier study reported the general distribution pattern of two subspecies M.m.castaneus and M.m.musculus in China. The established laboratory mouse strains have the 92% genomic origin from one subspecies M.m.domesticus. Therefore the Chinese taxa are extremely important to complement the genetic diversity of the laboratory stocks. Prior to a wise utilization of such valuable resources, a genetic polymorphism survey of the wild mice in China is highly necessary.The sampling regions of this study covered 11 provinces and 34 localities, which are related to 6 zoological regions in China. The study was performed to investigate the genetic polymorphisms of wild mice in natural population via the following major approaches:(1) DNA sequencing of mitochondrial control region with ABI 3730x1 was performed to investigate genetic polymorphisms in micro-regions, or intra-population genetic polymorphism. (2) Fluorescent PCR was performed to assay genotypes of both autosomal STR and ChrY STR, to discovery genetic polymorphisms of wild mice. (3) 7 established tagging SNP were genotyped with PCR-LDR technology and haplotype analysis was conducted to decipher the sub-specific status in China.The haplotype analysis with reference to known sequences of the M.m.castaneus and M.m.musculus subspecies found that 9 haplotypes exist in natural populations in China and H1(TCACATA), H9(TCATTTG)are the dominant halotypes, composing 24.32% and 52.51% respectively in all samples. The H1 and H9 and their related haplotypes are consistent with haplotypes drawn from known sequences of wild derived laboratory strains CAST/EiJ(M.m.castaneus) and PWD/Ph(M.m.musculus). The haplotype H1 of house mice in Yunnan, Tibet, Hubei and Xinjiang infers that distribution area spread from south to the northwest and regions along the Yangtze River. Northeastern and northern populations were found to be with M.m.musculus haplotype. Interestingly, eastern China has both of the above subspecies as inferred from the haplotype structure. Strikingly, Shanghai a typical southern city in China has a dominant M.m.musculus haplotype distribution, specifically 83% of the studied populations, Whereas Chongmin Island located in Yangtze river that is only miles away from Shanghai has 65% of house mice from M.m.castaneus subspecies. The sequencing data of the control region revealed a nucleotide replacement rate of 5.03%,2% higher than the HSV region in the human population. The sequencing data found that a 300bp segment in the control region of house mouse is highly conserved, while a 100bp segment has 28 polymorphic sites 63.6% of the total 44 sites identified in this study. The nucleotide composition rate of 57 polymorphic sites were analysis in 219 samples, guanine (G) was of the lowest rate in the sequenced region, around 12.6%, inferring that G replacement rarely occurs. The STR genotyping data found that an average of 14 alleles for each autosomal locus and 11 alleles for ChrY locus.The extensive genetic polymorphisms and great impact of human activities upon the distribution of the studied species were confirmed by this project. M.m.castaneus and M.m.musculus geographic structures in China were specified. The study implies that the taxa found in China can be used for genetic dissection of complex traits as these resources are highly complementary to established laboratory stocks.