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Genome wide linkage disequilibrium and genetic structure in Sicilian dairy sheep breeds.

Mastrangelo S, Di Gerlando R, Tolone M, Tortorici L, Sardina MT, Portolano B, International Sheep Genomics Consorti - BMC Genet. (2014)

Bottom Line: Pinzirita breed displayed the highest genetic diversity (He, Ne) whereas the lowest value was found in Valle del Belice breed.Our results indicate that breeds formed non-overlapping clusters and are clearly separated populations and that Comisana sheep breed does not constitute a homogenous population.The information generated from this study has important implications for the design and applications of association studies as well as for development of conservation and/or selection breeding programs.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento Scienze Agrarie e Forestali, Università degli Studi di Palermo, Viale delle Scienze, 90128, Palermo, Italy. salvatore.mastrangelo@unipa.it.

ABSTRACT

Background: The recent availability of sheep genome-wide SNP panels allows providing background information concerning genome structure in domestic animals. The aim of this work was to investigate the patterns of linkage disequilibrium (LD), the genetic diversity and population structure in Valle del Belice, Comisana, and Pinzirita dairy sheep breeds using the Illumina Ovine SNP50K Genotyping array.

Results: Average r (2) between adjacent SNPs across all chromosomes was 0.155 ± 0.204 for Valle del Belice, 0.156 ± 0.208 for Comisana, and 0.128 ± 0.188 for Pinzirita breeds, and some variations in LD value across chromosomes were observed, in particular for Valle del Belice and Comisana breeds. Average values of r (2) estimated for all pairwise combinations of SNPs pooled over all autosomes were 0.058 ± 0.023 for Valle del Belice, 0.056 ± 0.021 for Comisana, and 0.037 ± 0.017 for Pinzirita breeds. The LD declined as a function of distance and average r (2) was lower than the values observed in other sheep breeds. Consistency of results among the several used approaches (Principal component analysis, Bayesian clustering, F ST, Neighbor networks) showed that while Valle del Belice and Pinzirita breeds formed a unique cluster, Comisana breed showed the presence of substructure. In Valle del Belice breed, the high level of genetic differentiation within breed, the heterogeneous cluster in Admixture analysis, but at the same time the highest inbreeding coefficient, suggested that the breed had a wide genetic base with inbred individuals belonging to the same flock. The Sicilian breeds were characterized by low genetic differentiation and high level of admixture. Pinzirita breed displayed the highest genetic diversity (He, Ne) whereas the lowest value was found in Valle del Belice breed.

Conclusions: This study has reported for the first time estimates of LD and genetic diversity from a genome-wide perspective in Sicilian dairy sheep breeds. Our results indicate that breeds formed non-overlapping clusters and are clearly separated populations and that Comisana sheep breed does not constitute a homogenous population. The information generated from this study has important implications for the design and applications of association studies as well as for development of conservation and/or selection breeding programs.

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Linkage disequilibrium across the genome as a function of genomic distance. Valle del Belice (VDB), Comisana (COM) and Pinzirita (PIN) breeds.
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Fig1: Linkage disequilibrium across the genome as a function of genomic distance. Valle del Belice (VDB), Comisana (COM) and Pinzirita (PIN) breeds.

Mentions: The extent of LD was first evaluated for each adjacent SNP pairs. The r2 was used as measure of LD, because is the most suitable measure of LD for biallelic markers [11] and to avoid the influence of small sample size [12]. The average distances between adjacent SNP pairs for the whole autosomal genome were about 60 kb for Valle del Belice and Comisana, and 59 kb for Pinzirita sheep breeds (Table 1). The r2 ranged from 0.133 ± 0.187 for OAR14 to 0.182 ± 0.229 for OAR2 in Valle del Belice, from 0.134 ± 0.188 for OAR14 to 0.189 ± 0.237 for OAR2 in Comisana, whereas the lowest values among chromosomes were observed in Pinzirita, where r2 ranged from 0.107 ± 0.164 for OAR23 to 0.148 ± 0.208 for OAR2 (Table 1). Mean values of r2 estimated for all pairwise SNPs combinations pooled over all autosomes were 0.058 ± 0.023 for Valle del Belice, 0.056 ± 0.021 for Comisana, and 0.037 ± 0.017 for Pinzirita sheep breeds. In order to examine the decay of LD with physical distance, SNP pairs on autosomes were sorted into bins based on their inter-marker distance and average values of r2 were calculated for each bin. Pairwise r2 values were also averaged over all autosomes and plotted as a function of genomic distance between markers. Levels of pairwise LD decreased with increasing distance between SNPs, as reported in Figure 1 and Additional file 2: Table S2. For SNPs up to 50 kb apart the average r2 was 0.183, 0.181, and 0.154, for SNPs separated by 200–500 kb the average r2 was 0.074, 0.067, and 0.041, and when SNPs were separated by more than 2,000 kb the average r2 was 0.041, 0.042 and 0.029 in Valle del Belice, Comisana, and Pinzirita sheep breeds, respectively. These results could be attributed to recombination rate varying between and within chromosomes, differences in chromosome length, heterozygosity, genetic drift, and effect of selection [13]. Effect of selection on LD is dependent upon direction, intensity, duration, and consistency of selection over time. In fact, Pinzirita breed is not subject to breeding programs, while Comisana and Valle del Belice breeds are characterized by low selection pressure. The comparison of LD levels obtained in different studies is not straightforward, because of differences in several factors such as sample size, type of LD measures (D’ or r2), marker types (microsatellite or SNP), marker density and distribution, and population demography [13]. Moreover, so far, results of the extent of LD have been reported for wide-spread and important sheep breeds, and there is little knowledge about the degree of genome-wide LD in local sheep breeds. García-Gámez et al. [1] in a study on LD in Spanish Churra sheep breed reported an average r2 estimated for all pairwise combinations per chromosomes that ranged from 0.006 in OAR1 to 0.015 in OAR20, and an average r2 of 0.061 for SNPs separated by 200–500 kb, in agreement with our results. Usai et al. [14] in a study of LD in a sample of Sarda rams showed higher value with an average r2 over 1,000 kb of 0.072. Previous studies in five populations of domestic sheep based on microsatellite markers [6] and in wild sheep based on dense panel of SNPs [15] showed LD extends over long distance (r2 = 0.192 ± 0.131 for markers separated by 5–10 cM, and high levels of LD observed over 4 Mb, respectively). Levels of r2 for adjacent SNP pairs and all pairwise combinations of SNPs in Sicilian sheep breeds were lower than values observed in other livestock species such as pig [16,17], cattle [13,18], and horse [19,20]. These differences can be explained considering the intensive artificial selection to which commercial animal breeding populations (pig, cattle and horse) have been subjected for many generations and the ensuing reduction in effective population size. In fact, these species share a similar mating system using popular sires, whereas in ovine species, and in particular in Sicilian farming system, natural mating is the common practice. The decay of LD in a genome determines the power of QTL detection in association mapping studies and helps to determine the number of markers required for successful association mapping and genomic selection. Meuwissen et al. [4], in a simulation to predict genomic breeding values from dense markers across the whole genome with accuracies up to 0.85, found a required r2 level of 0.2. Qanbari et al. [13] considered r2 threshold of 0.25 as a useful LD value for association studies. In fact, species with extensive LD will require fewer markers than those with low levels of LD. Therefore, these results support the need to use more dense SNP panels for high power association mapping and genomic selection efficiency in future breeding programs for Sicilian dairy sheep breeds, and in particular for Pinzirita breed.Table 1


Genome wide linkage disequilibrium and genetic structure in Sicilian dairy sheep breeds.

Mastrangelo S, Di Gerlando R, Tolone M, Tortorici L, Sardina MT, Portolano B, International Sheep Genomics Consorti - BMC Genet. (2014)

Linkage disequilibrium across the genome as a function of genomic distance. Valle del Belice (VDB), Comisana (COM) and Pinzirita (PIN) breeds.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4197223&req=5

Fig1: Linkage disequilibrium across the genome as a function of genomic distance. Valle del Belice (VDB), Comisana (COM) and Pinzirita (PIN) breeds.
Mentions: The extent of LD was first evaluated for each adjacent SNP pairs. The r2 was used as measure of LD, because is the most suitable measure of LD for biallelic markers [11] and to avoid the influence of small sample size [12]. The average distances between adjacent SNP pairs for the whole autosomal genome were about 60 kb for Valle del Belice and Comisana, and 59 kb for Pinzirita sheep breeds (Table 1). The r2 ranged from 0.133 ± 0.187 for OAR14 to 0.182 ± 0.229 for OAR2 in Valle del Belice, from 0.134 ± 0.188 for OAR14 to 0.189 ± 0.237 for OAR2 in Comisana, whereas the lowest values among chromosomes were observed in Pinzirita, where r2 ranged from 0.107 ± 0.164 for OAR23 to 0.148 ± 0.208 for OAR2 (Table 1). Mean values of r2 estimated for all pairwise SNPs combinations pooled over all autosomes were 0.058 ± 0.023 for Valle del Belice, 0.056 ± 0.021 for Comisana, and 0.037 ± 0.017 for Pinzirita sheep breeds. In order to examine the decay of LD with physical distance, SNP pairs on autosomes were sorted into bins based on their inter-marker distance and average values of r2 were calculated for each bin. Pairwise r2 values were also averaged over all autosomes and plotted as a function of genomic distance between markers. Levels of pairwise LD decreased with increasing distance between SNPs, as reported in Figure 1 and Additional file 2: Table S2. For SNPs up to 50 kb apart the average r2 was 0.183, 0.181, and 0.154, for SNPs separated by 200–500 kb the average r2 was 0.074, 0.067, and 0.041, and when SNPs were separated by more than 2,000 kb the average r2 was 0.041, 0.042 and 0.029 in Valle del Belice, Comisana, and Pinzirita sheep breeds, respectively. These results could be attributed to recombination rate varying between and within chromosomes, differences in chromosome length, heterozygosity, genetic drift, and effect of selection [13]. Effect of selection on LD is dependent upon direction, intensity, duration, and consistency of selection over time. In fact, Pinzirita breed is not subject to breeding programs, while Comisana and Valle del Belice breeds are characterized by low selection pressure. The comparison of LD levels obtained in different studies is not straightforward, because of differences in several factors such as sample size, type of LD measures (D’ or r2), marker types (microsatellite or SNP), marker density and distribution, and population demography [13]. Moreover, so far, results of the extent of LD have been reported for wide-spread and important sheep breeds, and there is little knowledge about the degree of genome-wide LD in local sheep breeds. García-Gámez et al. [1] in a study on LD in Spanish Churra sheep breed reported an average r2 estimated for all pairwise combinations per chromosomes that ranged from 0.006 in OAR1 to 0.015 in OAR20, and an average r2 of 0.061 for SNPs separated by 200–500 kb, in agreement with our results. Usai et al. [14] in a study of LD in a sample of Sarda rams showed higher value with an average r2 over 1,000 kb of 0.072. Previous studies in five populations of domestic sheep based on microsatellite markers [6] and in wild sheep based on dense panel of SNPs [15] showed LD extends over long distance (r2 = 0.192 ± 0.131 for markers separated by 5–10 cM, and high levels of LD observed over 4 Mb, respectively). Levels of r2 for adjacent SNP pairs and all pairwise combinations of SNPs in Sicilian sheep breeds were lower than values observed in other livestock species such as pig [16,17], cattle [13,18], and horse [19,20]. These differences can be explained considering the intensive artificial selection to which commercial animal breeding populations (pig, cattle and horse) have been subjected for many generations and the ensuing reduction in effective population size. In fact, these species share a similar mating system using popular sires, whereas in ovine species, and in particular in Sicilian farming system, natural mating is the common practice. The decay of LD in a genome determines the power of QTL detection in association mapping studies and helps to determine the number of markers required for successful association mapping and genomic selection. Meuwissen et al. [4], in a simulation to predict genomic breeding values from dense markers across the whole genome with accuracies up to 0.85, found a required r2 level of 0.2. Qanbari et al. [13] considered r2 threshold of 0.25 as a useful LD value for association studies. In fact, species with extensive LD will require fewer markers than those with low levels of LD. Therefore, these results support the need to use more dense SNP panels for high power association mapping and genomic selection efficiency in future breeding programs for Sicilian dairy sheep breeds, and in particular for Pinzirita breed.Table 1

Bottom Line: Pinzirita breed displayed the highest genetic diversity (He, Ne) whereas the lowest value was found in Valle del Belice breed.Our results indicate that breeds formed non-overlapping clusters and are clearly separated populations and that Comisana sheep breed does not constitute a homogenous population.The information generated from this study has important implications for the design and applications of association studies as well as for development of conservation and/or selection breeding programs.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento Scienze Agrarie e Forestali, Università degli Studi di Palermo, Viale delle Scienze, 90128, Palermo, Italy. salvatore.mastrangelo@unipa.it.

ABSTRACT

Background: The recent availability of sheep genome-wide SNP panels allows providing background information concerning genome structure in domestic animals. The aim of this work was to investigate the patterns of linkage disequilibrium (LD), the genetic diversity and population structure in Valle del Belice, Comisana, and Pinzirita dairy sheep breeds using the Illumina Ovine SNP50K Genotyping array.

Results: Average r (2) between adjacent SNPs across all chromosomes was 0.155 ± 0.204 for Valle del Belice, 0.156 ± 0.208 for Comisana, and 0.128 ± 0.188 for Pinzirita breeds, and some variations in LD value across chromosomes were observed, in particular for Valle del Belice and Comisana breeds. Average values of r (2) estimated for all pairwise combinations of SNPs pooled over all autosomes were 0.058 ± 0.023 for Valle del Belice, 0.056 ± 0.021 for Comisana, and 0.037 ± 0.017 for Pinzirita breeds. The LD declined as a function of distance and average r (2) was lower than the values observed in other sheep breeds. Consistency of results among the several used approaches (Principal component analysis, Bayesian clustering, F ST, Neighbor networks) showed that while Valle del Belice and Pinzirita breeds formed a unique cluster, Comisana breed showed the presence of substructure. In Valle del Belice breed, the high level of genetic differentiation within breed, the heterogeneous cluster in Admixture analysis, but at the same time the highest inbreeding coefficient, suggested that the breed had a wide genetic base with inbred individuals belonging to the same flock. The Sicilian breeds were characterized by low genetic differentiation and high level of admixture. Pinzirita breed displayed the highest genetic diversity (He, Ne) whereas the lowest value was found in Valle del Belice breed.

Conclusions: This study has reported for the first time estimates of LD and genetic diversity from a genome-wide perspective in Sicilian dairy sheep breeds. Our results indicate that breeds formed non-overlapping clusters and are clearly separated populations and that Comisana sheep breed does not constitute a homogenous population. The information generated from this study has important implications for the design and applications of association studies as well as for development of conservation and/or selection breeding programs.

Show MeSH