Background: Runs of homozygosity(ROHs) are homozygous segments of the genome where the two haplotypes inherited from the parents are identical. The current availability of genotypes for a very large number of single n...Background: Runs of homozygosity(ROHs) are homozygous segments of the genome where the two haplotypes inherited from the parents are identical. The current availability of genotypes for a very large number of single nucleotide polymorphisms(SNPs) is leading to more accurate characterization of ROHs in the whole genome. Here,we investigated the occurrence and distribution of ROHs in 3,692 Large White pigs and compared estimates of inbreeding coefficients calculated based on ROHs(FROH), homozygosity(FHOM), genomic relationship matrix(FGRM)and pedigree(FPED). Furthermore, we identified genomic regions with high ROH frequencies and annotated their candidate genes.Results: In total, 176,182 ROHs were identified from 3,569 animals, and all individuals displayed at least one ROH longer than 1 Mb. The ROHs identified were unevenly distributed on the autosomes. The highest and lowest coverages of Sus scrofa chromosomes(SSC) by ROH were on SSC14 and SSC13, respectively. The highest pairwise correlation among the different inbreeding coefficient estimates was 0.95 between FROH_totaland FHOM, while the lowest was-0.083 between FGRMand FPED. The correlations between FPEDand FROHusing four classes of ROH lengths ranged from 0.18 to 0.37 and increased with increasing ROH length, except for ROH > 10 Mb. Twelve ROH islands were located on four chromosomes(SSC1, 4, 6 and 14). These ROH islands harboured genes associated with reproduction, muscular development, fat deposition and adaptation, such as SIRT1, MYPN, SETDB1 and PSMD4.Conclusion: FROHcan be used to accurately assess individual inbreeding levels compared to other inbreeding coefficient estimators. In the absence of pedigree records, FROHcan provide an alternative to inbreeding estimates.Our findings can be used not only to effectively increase the response to selection by appropriately managing the rate of inbreeding and minimizing the negative effects of inbreeding depression but also to help detect genomic regions with an effect on traits under selection.展开更多
Erhualian(E),Meishan(MS)and Mi(MI)pigs are excellent indigenous pig breeds in Chinese Taihu Basin,which have made great contributions to the genetic improvement of commercial pigs.Investigation of the genetic structur...Erhualian(E),Meishan(MS)and Mi(MI)pigs are excellent indigenous pig breeds in Chinese Taihu Basin,which have made great contributions to the genetic improvement of commercial pigs.Investigation of the genetic structure and inbreeding level of the 3 pig breeds is of great significance for the sustainable breeding of commercial pigs.The length and number of runs of homozygosity(ROH)as well as the frequency of genomes covered by ROH can be used as indicators to evaluate the level of inbreeding and the origin of the population.In this study,the ROH characteristics of E,MS,MI and Landrace(L)pigs were analyzed by SLAF-seq data,and the inbreeding coefficient based on ROH(F_(ROH))was calculated.In addition,we have identified candidate genes in the genomic regions associated with ROH.A total of10568 ROH were detected in 116 individuals of 4 pig breeds.The analysis showed that there were significant differences in genetic structure between 3 Taihu Basin pig breeds and L,and the genetic structure of E and MI was similar.The results of F_(ROH)showed that the inbreeding level of MS was the highest(0.25±0.07),while E and MI were lower than L.Compared with the other 3 pig populations,MS showed a higher frequency of long ROH(>5 Mb),indicating higher inbreeding in MS in recent generations.A large number of candidate genes related to reproductive traits are located in the genomic regions with a high frequency of ROH,and these genes are expected to be used as candidate genes in marker-assisted selection(MAS)breeding programs.Our findings can provide theoretical support for genetic conservation and genetic improvement of 3 pig breeds in Chinese Taihu Basin.展开更多
Runs of homozygosity （ROHs） are a class of important but poorly studied genomic variations and may be in- volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung canc...Runs of homozygosity （ROHs） are a class of important but poorly studied genomic variations and may be in- volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung cancer, we performed a genome-wide ROH analysis of a subset of a previous genome-wide case-control study （1,473 cases and 1,962 controls） in a Han Chinese population. ROHs were classified into two classes, based on lengths, intermedi- ate and long ROils, to evaluate their association with lung cancer risk using existing genome-wide single nucleofide polymorphism （SNP） data. We found that the overall level of intermediate ROHs was significantly associated with a decreased risk of lung cancer （odds ratio = 0.63; 95% confidence interval： 0.51-0.77; P = 4.78 × 10-6 ）, while the long ROHs seemed to be a risk factor of lung cancer. We also identified one ROH region at 14q23A that was con- sistently associated with lung cancer risk in the study. These results indicated that ROHs may be a new class of variation which may be associated with lung cancer risk, and genetic variants at 14q23.1 may be involved in the development of lung cancer.展开更多
Global climate change has increased concerns regarding biodiversity loss.However,many key conservation issues still required further research,including demographic history,deleterious mutation load,adaptive evolution,...Global climate change has increased concerns regarding biodiversity loss.However,many key conservation issues still required further research,including demographic history,deleterious mutation load,adaptive evolution,and putative introgression.Here we generated the first chromosome-level genome of the endangered Chinese hazelnut,Corylus chinensis,and compared the genomic signatures with its sympatric widespread C.kwechowensis-C yunnanensis complex.We found large genome rearrangements across all Corylus species and identified species-specific expanded gene families that may be involved in adaptation.Population genomics revealed that both C.chinensis and the C.kwechowensis-C.yunnanensis complex had diverged into two genetic lineages,forming a consistent pattern of southwestern-northern differentiation.Population size of the narrow southwestern lineages of both species have decreased continuously since the late Miocene,whereas the widespread northern lineages have remained stable(C.chinensis) or have even recovered from population bottlenecks(C.kwechowensis-C.yunnanensis complex) during the Quaternary.Compared with C.kwechowensis-C. yunnanensis complex,C.chinensis showed significantly lower genomic diversity and higher inbreeding level.However,C.chinensis carried significantly fewer deleterious mutations than C.kwechowensis-C. yunnanensis complex,as more effective purging selection reduced the accumulation of homozygous variants.We also detected signals of positive selection and adaptive introgression in different lineages,which facilitated the accumulation of favorable variants and formation of local adaptation.Hence,both types of selection and exogenous introgression could have mitigated inbreeding and facilitated survival and persistence of C.chinensis.Overall,our study provides critical insights into lineage differentiation,local adaptation,and the potential for future recovery of endangered trees.展开更多
Background:A run of homozygosity(ROH)is a consecutive tract of homozygous genotypes in an individual that indicates it has inherited the same ancestral haplotype from both parents.Genomic inbreeding can be quantified ...Background:A run of homozygosity(ROH)is a consecutive tract of homozygous genotypes in an individual that indicates it has inherited the same ancestral haplotype from both parents.Genomic inbreeding can be quantified based on ROH.Genomic regions enriched with ROH may be indicative of selection sweeps and are known as ROH islands.We carried out ROH analyses in five Chinese indigenous sheep breeds;Altay sheep(n=50 individuals),Large-tailed Han sheep(n=50),Hulun Buir sheep(n=150),Short-tailed grassland sheep(n=150),and Tibetan sheep(n=50),using genotypes from an Ovine Infinium HD SNP BeadChip.Results:A total of 18,288 ROH were identified.The average number of ROH per individual across the five sheep breeds ranged from 39(Hulun Buir sheep)to 78(Large-tailed Han sheep)and the average length of ROH ranged from 0.929 Mb(Hulun Buir sheep)to 2.544 Mb(Large-tailed Han sheep).The effective population size(Ne)of Altay sheep,Large-tailed Han sheep,Hulun Buir sheep,Short-tailed grassland sheep and Tibetan sheep were estimated to be 81,78,253,238 and 70 five generations ago.The highest ROH-based inbreeding estimate(FROH)was 0.0808 in Large-tailed Han sheep,whereas the lowest F_(ROH)was 0.0148 in Hulun Buir sheep.Furthermore,the highest proportion of long ROH fragments(>5 Mb)was observed in the Large-tailed Han sheep breed which indicated recent inbreeding.In total,49 ROH islands(the top 0.1% of the SNPs most commonly observed in ROH)were identified in the five sheep breeds.Three ROH islands were common to all the five sheep breeds,and were located on OAR2:12.2-12.3 Mb,OAR12:78.4-79.1 Mb and OAR13:53.0-53.6 Mb.Three breed-specific ROH islands were observed in Altay sheep(OAR15:3.4-3.8 Mb),Large-tailed Han sheep(ORA17:53.5-53.8 Mb)and Tibetan sheep(ORA5:19.8-20.2 Mb).Collectively,the ROH islands harbored 78 unique genes,including 19 genes that have been documented as having associations with tail types,adaptation,growth,body size,reproduction or immune response.Conclusion:Different ROH patterns were observed in five Chinese indigenous sheep breeds,which reflected their different population histories.Large-tailed Han sheep had the highest genomic inbreeding coefficients and the highest proportion of long ROH fragments indicating recent inbreeding.Candidate genes in ROH islands could be used to illustrate the genetic characteristics of these five sheep breeds.Our findings contribute to the understanding of genetic diversity and population demography,and help design and implement breeding and conservation strategies for Chinese sheep.展开更多
基金supported by the Natural Science Foundation of China (No.31572357) to FPZthe National Swine Industry Technology System(CARS-35) to LXW。
文摘Background: Runs of homozygosity(ROHs) are homozygous segments of the genome where the two haplotypes inherited from the parents are identical. The current availability of genotypes for a very large number of single nucleotide polymorphisms(SNPs) is leading to more accurate characterization of ROHs in the whole genome. Here,we investigated the occurrence and distribution of ROHs in 3,692 Large White pigs and compared estimates of inbreeding coefficients calculated based on ROHs(FROH), homozygosity(FHOM), genomic relationship matrix(FGRM)and pedigree(FPED). Furthermore, we identified genomic regions with high ROH frequencies and annotated their candidate genes.Results: In total, 176,182 ROHs were identified from 3,569 animals, and all individuals displayed at least one ROH longer than 1 Mb. The ROHs identified were unevenly distributed on the autosomes. The highest and lowest coverages of Sus scrofa chromosomes(SSC) by ROH were on SSC14 and SSC13, respectively. The highest pairwise correlation among the different inbreeding coefficient estimates was 0.95 between FROH_totaland FHOM, while the lowest was-0.083 between FGRMand FPED. The correlations between FPEDand FROHusing four classes of ROH lengths ranged from 0.18 to 0.37 and increased with increasing ROH length, except for ROH > 10 Mb. Twelve ROH islands were located on four chromosomes(SSC1, 4, 6 and 14). These ROH islands harboured genes associated with reproduction, muscular development, fat deposition and adaptation, such as SIRT1, MYPN, SETDB1 and PSMD4.Conclusion: FROHcan be used to accurately assess individual inbreeding levels compared to other inbreeding coefficient estimators. In the absence of pedigree records, FROHcan provide an alternative to inbreeding estimates.Our findings can be used not only to effectively increase the response to selection by appropriately managing the rate of inbreeding and minimizing the negative effects of inbreeding depression but also to help detect genomic regions with an effect on traits under selection.
基金supported by the Jiangsu Agricultural Science and Technology Innovation Found,China(SCX(20)3290)the Open Foundation of Key Laboratory of Urban Agriculture,Ministry of Agriculture and Rural Affairs of China(201906)the Joint Research Project on Pig Breeding in Anhui Province,China(340000211260001000431)。
文摘Erhualian(E),Meishan(MS)and Mi(MI)pigs are excellent indigenous pig breeds in Chinese Taihu Basin,which have made great contributions to the genetic improvement of commercial pigs.Investigation of the genetic structure and inbreeding level of the 3 pig breeds is of great significance for the sustainable breeding of commercial pigs.The length and number of runs of homozygosity(ROH)as well as the frequency of genomes covered by ROH can be used as indicators to evaluate the level of inbreeding and the origin of the population.In this study,the ROH characteristics of E,MS,MI and Landrace(L)pigs were analyzed by SLAF-seq data,and the inbreeding coefficient based on ROH(F_(ROH))was calculated.In addition,we have identified candidate genes in the genomic regions associated with ROH.A total of10568 ROH were detected in 116 individuals of 4 pig breeds.The analysis showed that there were significant differences in genetic structure between 3 Taihu Basin pig breeds and L,and the genetic structure of E and MI was similar.The results of F_(ROH)showed that the inbreeding level of MS was the highest(0.25±0.07),while E and MI were lower than L.Compared with the other 3 pig populations,MS showed a higher frequency of long ROH(>5 Mb),indicating higher inbreeding in MS in recent generations.A large number of candidate genes related to reproductive traits are located in the genomic regions with a high frequency of ROH,and these genes are expected to be used as candidate genes in marker-assisted selection(MAS)breeding programs.Our findings can provide theoretical support for genetic conservation and genetic improvement of 3 pig breeds in Chinese Taihu Basin.
基金supported in part the by National Natural Science Foundation of China(81230067,81270044 and 30901233)Doctoral Fund of Ministry of Education of China(20093234110001)+1 种基金New Century Excellent Talents in University(NCET-10-0178)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Runs of homozygosity （ROHs） are a class of important but poorly studied genomic variations and may be in- volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung cancer, we performed a genome-wide ROH analysis of a subset of a previous genome-wide case-control study （1,473 cases and 1,962 controls） in a Han Chinese population. ROHs were classified into two classes, based on lengths, intermedi- ate and long ROils, to evaluate their association with lung cancer risk using existing genome-wide single nucleofide polymorphism （SNP） data. We found that the overall level of intermediate ROHs was significantly associated with a decreased risk of lung cancer （odds ratio = 0.63; 95% confidence interval： 0.51-0.77; P = 4.78 × 10-6 ）, while the long ROHs seemed to be a risk factor of lung cancer. We also identified one ROH region at 14q23A that was con- sistently associated with lung cancer risk in the study. These results indicated that ROHs may be a new class of variation which may be associated with lung cancer risk, and genetic variants at 14q23.1 may be involved in the development of lung cancer.
基金supported by the National Natural Science Foundation of China(Grant No.32101541)the National Key R&D Program of China(Grant No.2022YFD2200400).
文摘Global climate change has increased concerns regarding biodiversity loss.However,many key conservation issues still required further research,including demographic history,deleterious mutation load,adaptive evolution,and putative introgression.Here we generated the first chromosome-level genome of the endangered Chinese hazelnut,Corylus chinensis,and compared the genomic signatures with its sympatric widespread C.kwechowensis-C yunnanensis complex.We found large genome rearrangements across all Corylus species and identified species-specific expanded gene families that may be involved in adaptation.Population genomics revealed that both C.chinensis and the C.kwechowensis-C.yunnanensis complex had diverged into two genetic lineages,forming a consistent pattern of southwestern-northern differentiation.Population size of the narrow southwestern lineages of both species have decreased continuously since the late Miocene,whereas the widespread northern lineages have remained stable(C.chinensis) or have even recovered from population bottlenecks(C.kwechowensis-C.yunnanensis complex) during the Quaternary.Compared with C.kwechowensis-C. yunnanensis complex,C.chinensis showed significantly lower genomic diversity and higher inbreeding level.However,C.chinensis carried significantly fewer deleterious mutations than C.kwechowensis-C. yunnanensis complex,as more effective purging selection reduced the accumulation of homozygous variants.We also detected signals of positive selection and adaptive introgression in different lineages,which facilitated the accumulation of favorable variants and formation of local adaptation.Hence,both types of selection and exogenous introgression could have mitigated inbreeding and facilitated survival and persistence of C.chinensis.Overall,our study provides critical insights into lineage differentiation,local adaptation,and the potential for future recovery of endangered trees.
基金funded by the Natural Science Foundations of China(No.31572357)to FPZAgricultural Science and Technology Innovation Program(ASTIP-IAS02)to LXW.
文摘Background:A run of homozygosity(ROH)is a consecutive tract of homozygous genotypes in an individual that indicates it has inherited the same ancestral haplotype from both parents.Genomic inbreeding can be quantified based on ROH.Genomic regions enriched with ROH may be indicative of selection sweeps and are known as ROH islands.We carried out ROH analyses in five Chinese indigenous sheep breeds;Altay sheep(n=50 individuals),Large-tailed Han sheep(n=50),Hulun Buir sheep(n=150),Short-tailed grassland sheep(n=150),and Tibetan sheep(n=50),using genotypes from an Ovine Infinium HD SNP BeadChip.Results:A total of 18,288 ROH were identified.The average number of ROH per individual across the five sheep breeds ranged from 39(Hulun Buir sheep)to 78(Large-tailed Han sheep)and the average length of ROH ranged from 0.929 Mb(Hulun Buir sheep)to 2.544 Mb(Large-tailed Han sheep).The effective population size(Ne)of Altay sheep,Large-tailed Han sheep,Hulun Buir sheep,Short-tailed grassland sheep and Tibetan sheep were estimated to be 81,78,253,238 and 70 five generations ago.The highest ROH-based inbreeding estimate(FROH)was 0.0808 in Large-tailed Han sheep,whereas the lowest F_(ROH)was 0.0148 in Hulun Buir sheep.Furthermore,the highest proportion of long ROH fragments(>5 Mb)was observed in the Large-tailed Han sheep breed which indicated recent inbreeding.In total,49 ROH islands(the top 0.1% of the SNPs most commonly observed in ROH)were identified in the five sheep breeds.Three ROH islands were common to all the five sheep breeds,and were located on OAR2:12.2-12.3 Mb,OAR12:78.4-79.1 Mb and OAR13:53.0-53.6 Mb.Three breed-specific ROH islands were observed in Altay sheep(OAR15:3.4-3.8 Mb),Large-tailed Han sheep(ORA17:53.5-53.8 Mb)and Tibetan sheep(ORA5:19.8-20.2 Mb).Collectively,the ROH islands harbored 78 unique genes,including 19 genes that have been documented as having associations with tail types,adaptation,growth,body size,reproduction or immune response.Conclusion:Different ROH patterns were observed in five Chinese indigenous sheep breeds,which reflected their different population histories.Large-tailed Han sheep had the highest genomic inbreeding coefficients and the highest proportion of long ROH fragments indicating recent inbreeding.Candidate genes in ROH islands could be used to illustrate the genetic characteristics of these five sheep breeds.Our findings contribute to the understanding of genetic diversity and population demography,and help design and implement breeding and conservation strategies for Chinese sheep.
