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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 proportion of all genome-wide non-reference homozygotes falling in ROH regions for non-deleterious variants, nonsense variants, and loss of function nonsense variants versus the genome ROH coverage for individuals in the “low ROH” and “high ROH” groups. A: Any ROH region; B: Short; C: Medium; and D: Long ROH regions
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Fig6: The proportion of all genome-wide non-reference homozygotes falling in ROH regions for non-deleterious variants, nonsense variants, and loss of function nonsense variants versus the genome ROH coverage for individuals in the “low ROH” and “high ROH” groups. A: Any ROH region; B: Short; C: Medium; and D: Long ROH regions

Mentions: Additional file 13: Table S4 and Additional file 14: Table S5 report nonsense and loss of function nonsense sites, respectively, with counts for reference homozygotes (0/0), heterozygotes (0/1), and non-reference homozygotes (1/1), which fell into ROH and non-ROH regions. Figure 6a shows nonsense mutation distribution across all ROH. For low-ROH individuals, the mean proportion of non-deleterious homozygote variants falling in ROH marginally exceeded the nonsense or loss of function variants. For high-ROH individuals, however, the proportion of non-deleterious homozygotes within ROH was lower than for nonsense homozygotes. When ROH are segregated by size (Fig. 6b–d), including individuals with high genomic ROH coverage, the proportion of nonsense homozygotes in medium ROH was greater than that of non-deleterious homozygotes, while the proportion of nonsense homozygotes was slightly lower than non-deleterious homozygotes for large ROH. This is consistent with the finding that high-ROH individuals exhibited an increased proportion of damaging homozygotes (nonsense mutations) in ROH of any size (Fig. 6a), primarily driven by medium ROH (Fig. 6d).Fig. 6


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 proportion of all genome-wide non-reference homozygotes falling in ROH regions for non-deleterious variants, nonsense variants, and loss of function nonsense variants versus the genome ROH coverage for individuals in the “low ROH” and “high ROH” groups. A: Any ROH region; B: Short; C: Medium; and D: Long ROH regions
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: The proportion of all genome-wide non-reference homozygotes falling in ROH regions for non-deleterious variants, nonsense variants, and loss of function nonsense variants versus the genome ROH coverage for individuals in the “low ROH” and “high ROH” groups. A: Any ROH region; B: Short; C: Medium; and D: Long ROH regions
Mentions: Additional file 13: Table S4 and Additional file 14: Table S5 report nonsense and loss of function nonsense sites, respectively, with counts for reference homozygotes (0/0), heterozygotes (0/1), and non-reference homozygotes (1/1), which fell into ROH and non-ROH regions. Figure 6a shows nonsense mutation distribution across all ROH. For low-ROH individuals, the mean proportion of non-deleterious homozygote variants falling in ROH marginally exceeded the nonsense or loss of function variants. For high-ROH individuals, however, the proportion of non-deleterious homozygotes within ROH was lower than for nonsense homozygotes. When ROH are segregated by size (Fig. 6b–d), including individuals with high genomic ROH coverage, the proportion of nonsense homozygotes in medium ROH was greater than that of non-deleterious homozygotes, while the proportion of nonsense homozygotes was slightly lower than non-deleterious homozygotes for large ROH. This is consistent with the finding that high-ROH individuals exhibited an increased proportion of damaging homozygotes (nonsense mutations) in ROH of any size (Fig. 6a), primarily driven by medium ROH (Fig. 6d).Fig. 6

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