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Runs of homozygosity and distribution of functional variants in the cattle genome.

Zhang Q, Guldbrandtsen B, Bosse M, Lund MS, Sahana G - BMC Genomics (2015)

Bottom Line: We also found that increased enrichment of deleterious variants was significantly higher in short (<100 kbp) and medium (0.1 to 3 Mbp) ROH regions compared with long (>3 Mbp) ROH regions (P < 0.001), which is different than what has been observed in the human genome.These patterns are different from those in the human genome but consistent with the natural history of cattle populations, which is confirmed by the significant correlation between shared short ROH regions and regions putatively under selection.These findings contribute to understanding the effects of inbreeding and probably selection in shaping the distribution of functional variants in the cattle genome.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, DK-8830, Denmark. Qianqian.zhang@mbg.au.dk.

ABSTRACT

Background: Recent developments in sequencing technology have facilitated widespread investigations of genomic variants, including continuous stretches of homozygous genomic regions. For cattle, a large proportion of these runs of homozygosity (ROH) are likely the result of inbreeding due to the accumulation of elite alleles from long-term selective breeding programs. In the present study, ROH were characterized in four cattle breeds with whole genome sequence data and the distribution of predicted functional variants was detected in ROH regions and across different ROH length classes.

Results: On average, 19.5% of the genome was located in ROH across four cattle breeds. There were an average of 715.5 ROH per genome with an average size of ~750 kbp, ranging from 10 (minimum size considered) to 49,290 kbp. There was a significant correlation between shared short ROH regions and regions putatively under selection (p < 0.001). By investigating the relationship between ROH and the predicted deleterious and non-deleterious variants, we gained insight into the distribution of functional variation in inbred (ROH) regions. Predicted deleterious variants were more enriched in ROH regions than predicted non-deleterious variants, which is consistent with observations in the human genome. We also found that increased enrichment of deleterious variants was significantly higher in short (<100 kbp) and medium (0.1 to 3 Mbp) ROH regions compared with long (>3 Mbp) ROH regions (P < 0.001), which is different than what has been observed in the human genome.

Conclusions: This study illustrates the distribution of ROH and functional variants within ROH in cattle populations. These patterns are different from those in the human genome but consistent with the natural history of cattle populations, which is confirmed by the significant correlation between shared short ROH regions and regions putatively under selection. These findings contribute to understanding the effects of inbreeding and probably selection in shaping the distribution of functional variants in the cattle genome.

No MeSH data available.


Related in: MedlinePlus

The genome-wide proportion of all non-reference homozygotes falling in different ROH sizes versus genome ROH coverage for each individual. Red, orange, and black points represent deleterious homozygotes in large, medium, and small ROH regions, respectively
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Fig5: The genome-wide proportion of all non-reference homozygotes falling in different ROH sizes versus genome ROH coverage for each individual. Red, orange, and black points represent deleterious homozygotes in large, medium, and small ROH regions, respectively

Mentions: These results show that deleterious homozygotes occur more frequently in ROH than non-deleterious homozygotes. Additionally, when the proportion of deleterious homozygotes within large ROH (fi,Ld) is compared to the proportion within small ROH (fi,Sd), there was a substantially higher proportion of genome-wide deleterious homozygotes in small and medium vs. large ROH especially in individuals with moderate to high ROH coverage proportions (Fig. 5). Given that ROH coverage (Fig. 1) for all individuals across the four breeds differed (as previously mentioned). Therefore, statistical tests for each size group were robust across the breeds and there were different ROH coverage groups across all individuals (Additional file 10: Table S1). Similar trends were observed for each ROH size group, and significantly different degrees of enrichment were observed within each size group.Fig. 5


Runs of homozygosity and distribution of functional variants in the cattle genome.

Zhang Q, Guldbrandtsen B, Bosse M, Lund MS, Sahana G - BMC Genomics (2015)

The genome-wide proportion of all non-reference homozygotes falling in different ROH sizes versus genome ROH coverage for each individual. Red, orange, and black points represent deleterious homozygotes in large, medium, and small ROH regions, respectively
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4508970&req=5

Fig5: The genome-wide proportion of all non-reference homozygotes falling in different ROH sizes versus genome ROH coverage for each individual. Red, orange, and black points represent deleterious homozygotes in large, medium, and small ROH regions, respectively
Mentions: These results show that deleterious homozygotes occur more frequently in ROH than non-deleterious homozygotes. Additionally, when the proportion of deleterious homozygotes within large ROH (fi,Ld) is compared to the proportion within small ROH (fi,Sd), there was a substantially higher proportion of genome-wide deleterious homozygotes in small and medium vs. large ROH especially in individuals with moderate to high ROH coverage proportions (Fig. 5). Given that ROH coverage (Fig. 1) for all individuals across the four breeds differed (as previously mentioned). Therefore, statistical tests for each size group were robust across the breeds and there were different ROH coverage groups across all individuals (Additional file 10: Table S1). Similar trends were observed for each ROH size group, and significantly different degrees of enrichment were observed within each size group.Fig. 5

Bottom Line: We also found that increased enrichment of deleterious variants was significantly higher in short (<100 kbp) and medium (0.1 to 3 Mbp) ROH regions compared with long (>3 Mbp) ROH regions (P < 0.001), which is different than what has been observed in the human genome.These patterns are different from those in the human genome but consistent with the natural history of cattle populations, which is confirmed by the significant correlation between shared short ROH regions and regions putatively under selection.These findings contribute to understanding the effects of inbreeding and probably selection in shaping the distribution of functional variants in the cattle genome.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, DK-8830, Denmark. Qianqian.zhang@mbg.au.dk.

ABSTRACT

Background: Recent developments in sequencing technology have facilitated widespread investigations of genomic variants, including continuous stretches of homozygous genomic regions. For cattle, a large proportion of these runs of homozygosity (ROH) are likely the result of inbreeding due to the accumulation of elite alleles from long-term selective breeding programs. In the present study, ROH were characterized in four cattle breeds with whole genome sequence data and the distribution of predicted functional variants was detected in ROH regions and across different ROH length classes.

Results: On average, 19.5% of the genome was located in ROH across four cattle breeds. There were an average of 715.5 ROH per genome with an average size of ~750 kbp, ranging from 10 (minimum size considered) to 49,290 kbp. There was a significant correlation between shared short ROH regions and regions putatively under selection (p < 0.001). By investigating the relationship between ROH and the predicted deleterious and non-deleterious variants, we gained insight into the distribution of functional variation in inbred (ROH) regions. Predicted deleterious variants were more enriched in ROH regions than predicted non-deleterious variants, which is consistent with observations in the human genome. We also found that increased enrichment of deleterious variants was significantly higher in short (<100 kbp) and medium (0.1 to 3 Mbp) ROH regions compared with long (>3 Mbp) ROH regions (P < 0.001), which is different than what has been observed in the human genome.

Conclusions: This study illustrates the distribution of ROH and functional variants within ROH in cattle populations. These patterns are different from those in the human genome but consistent with the natural history of cattle populations, which is confirmed by the significant correlation between shared short ROH regions and regions putatively under selection. These findings contribute to understanding the effects of inbreeding and probably selection in shaping the distribution of functional variants in the cattle genome.

No MeSH data available.


Related in: MedlinePlus