Genome-Wide Scan For Runs Of Homozygosity Identifies Candidate Genes In Sheep With Different Density SNP Chips

Runs of homozygosity（ROH）are contiguous segments of homozygous genotypes in diploid creatures that are present in an individual due to parents transmitting identical haplotypes to their offspring.Performation of ROH detection can calculate genomic inbreeding coefficient,refer population history,identify candidate gene and assess genetic diversity.The aim of this study was to use different density SNP data of sheep to perform genome-wide ROH detection,identify candidate gene,analysize linkage disequilibrium and estimate effective population size.The specific research content is as follows:（1）A total of 407 individuals of five Chinese indigenous sheep populations were genotyped using Illumina Ovine 600 K SNP chips.The genome-wide ROH in five sheep population were detected.The number,length,frequency and distribution of ROH in different sheep groups were counted and inbreeding coefficient F_ROH based on ROH weas calculated.The inbreeding history was deduced based on the length of ROH fragment and candidate genes related to economic traits of sheep were searched according to the high frequency region of ROH.The effective population size of five sheep groups in different generations was calculated according to the linkage disequilibrium information.A total of 18490 ROH fragments were detected in five sheep groups.The average number of ROH per individual of different sheep groups ranged from 39.62（Hulun Buir fat-tail sheep）to 77.82（Large-tailed Han sheep）and the average length of ROH of different sheep groups ranged from 0.939 Mb（Hulun Buir fat-tail sheep）to 2.568 Mb（Large-tailed Han sheep）.A high proportion of long ROH fragment in the Large-tailed Han sheep group indicated that it had experienced strong inbreeding in recent generations.The genomic inbreeding coefficient of the five sheep populations ranged from 0.0152（Hulun Buir fat-tail sheep）to 0.0815（Large-tailed Han sheep）.222 genes were identified based on high frequency region of ROH,and 16 candidate genes related to economic traits of sheep were found through literature search.For example,CSRP1,TNNI1 and LATS2were associated with growth and development traits.CSF2 and IL3 were related to immunity response.NPBWR2,TPD52L2 and HOXA11 involved reproduction traits.The linkage disequilibrium analysis shows that the extent of linkage disequilibrium of Hulun Buir fat-tail sheep and Hulun Buir thin-tail sheep is lower than other three groups.The results of effective population size showed that the effective population size of five sheep groups tended to decrease with the decrease of generations.Until five generations ago,the effective population size of Altay sheep,Large-tailed Han sheep,h Hulun Buir fat-tail sheep,Hulun Buir thin-tail sheep and Tibetan sheep from Qinghai were 81,78,253,238 and 70,respectively.The genomic inbreeding coefficient calculated by ROH and the effective population size calculated based on linkage disequilibrium would provide reference for breeding,preservation,inbreeding control and genetic diversity evaluation of five sheep populations.Large-tailed Han sheep had the highest genomic inbreeding coefficient and had experienced strong inbreeding in recent generations which indicated measures should be taken to prevent the further rise of inbreeding.The sixteen genes identified could be used as candidate genes of sheep breeding.（2）A total of 440 individuals in ten sheep populations at home and abroad were genotyped by the Illumina Ovine SNP 50 K chip.The genome-wide ROH in ten sheep population were detected with chip data,the number,length,frequency and distribution of ROH in different sheep groups were counted,and the genomic inbreeding coefficient F_ROH were calculated based on the length of ROH.The inbreeding history was deduced based on the length of ROH fragment,and candidate genes related to economic traits of sheep were searched according to the high frequency region of ROH.A total of 25,920 ROH fragments were detected in ten sheep groups and there were obvious differences in the number,length,frequency and distribution of ROH among different sheep groups.The average number of ROH per individual of different sheep groups ranged from 10.17（Sunite）to 95.99（Dorper）,and the average length of ROH of different sheep groups ranged from 2..04 Mb（Tibetan sheep in sichaun）to 4.71 Mb（Lop）.The genomic inbreeding coefficient of Dorper and German Mutton Merino sheep were significantly higher than the indigenous sheep populations in China.Dorper sheep（0.172）and Sunite sheep（0.0103）had the highest and lowest genomic inbreeding coefficient,respectively.In Chinese indigenous sheep population,Tibetan sheep from Tibet and Large-tailed Han sheep had the highest genomic inbreeding coefficients,which were0.0849 and 0.0715,respectively.Sunite sheep and Tibetan sheep from sichuan had the lowest genomic inbreeding coefficient,which were 0.0103 and 0.0218,respectively.In addition,the high proportion of long ROH segments in the Dorper sheep,Tibetan sheep from tibet and Lop sheep population indicated strong inbreeding in recent generations.301 genes were identified based on high frequency region of ROH,and 26 candidate genes related to economic traits of sheep were found through literature search.For example,NCAPG,LCORL,PRKAA2,FAIM2 and HYDIN were associated with growth and development traits.LEPR,WNT10B and NCKAP5L were related to fat metabolism.CDIPT,CAPN3 and FGF9 involved meat quality and carcass traits.The genomic inbreeding coefficient calculated by ROH and inbreeding history evaluated by ROH would provide reference for breeding and genetic resource protection of the ten sheep populations.The twenty-six identified genes related to economic traits of sheep could be used as candidate genes for marker assisted selection of sheep.