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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

Deleterious non-reference homozygotes versus the genome ROH coverage in each individual. Red points represent the number of deleterious homozygotes falling within ROH regions and black points represent the number of deleterious homozygotes falling outside ROH regions
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Fig3: Deleterious non-reference homozygotes versus the genome ROH coverage in each individual. Red points represent the number of deleterious homozygotes falling within ROH regions and black points represent the number of deleterious homozygotes falling outside ROH regions

Mentions: Figure 3 shows the total number of deleterious non-reference homozygotes (1/1) as a function of the total proportion of the genome covered by ROH (Gi,R) for all sequenced individuals. As ROH coverage increased (high Gi,R values), a greater number of homozygotes were observed within ROH, which was consistent with findings from the human genome [24]. There was a very strong positive correlation between the number of deleterious homozygotes and the genomic ROH proportion (Pearson r = 0.93, slope = 1568.76, intercept = −57.63). Similarly, the number of homozygotes outside of ROH decreased with the genomic ROH proportion due to smaller non-ROH regions as ROH coverage increased. As expected, there was a weak negative correlation between deleterious homozygotes outside ROH and the genomic ROH proportions (Pearson r = −0.12, slope = −98.67, intercept = 693.63). Compared with data from the human genome, the decreased slope for non-ROH regions was much shallower than the increased slope for ROH regions [24]. However, this indicates that the increased deleterious homozygotes in ROH regions exceed deleterious homozygote declines in non-ROH regions in cattle. Similar to the human genome [24], the fitted lines also predict that, on average, individual non-inbred cattle (Gi,R ≈ 0) carry approximately 694 deleterious homozygous variants. An increased in ROH coverage by 10 % will increase the expected deleterious homozygote numbers in ROH regions by 157 and decrease the expected number of deleterious homozygotes in non-ROH regions by 10, yielding an expected net increase of 147 deleterious homozygotes.Fig. 3


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)

Deleterious non-reference homozygotes versus the genome ROH coverage in each individual. Red points represent the number of deleterious homozygotes falling within ROH regions and black points represent the number of deleterious homozygotes falling outside ROH regions
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Deleterious non-reference homozygotes versus the genome ROH coverage in each individual. Red points represent the number of deleterious homozygotes falling within ROH regions and black points represent the number of deleterious homozygotes falling outside ROH regions
Mentions: Figure 3 shows the total number of deleterious non-reference homozygotes (1/1) as a function of the total proportion of the genome covered by ROH (Gi,R) for all sequenced individuals. As ROH coverage increased (high Gi,R values), a greater number of homozygotes were observed within ROH, which was consistent with findings from the human genome [24]. There was a very strong positive correlation between the number of deleterious homozygotes and the genomic ROH proportion (Pearson r = 0.93, slope = 1568.76, intercept = −57.63). Similarly, the number of homozygotes outside of ROH decreased with the genomic ROH proportion due to smaller non-ROH regions as ROH coverage increased. As expected, there was a weak negative correlation between deleterious homozygotes outside ROH and the genomic ROH proportions (Pearson r = −0.12, slope = −98.67, intercept = 693.63). Compared with data from the human genome, the decreased slope for non-ROH regions was much shallower than the increased slope for ROH regions [24]. However, this indicates that the increased deleterious homozygotes in ROH regions exceed deleterious homozygote declines in non-ROH regions in cattle. Similar to the human genome [24], the fitted lines also predict that, on average, individual non-inbred cattle (Gi,R ≈ 0) carry approximately 694 deleterious homozygous variants. An increased in ROH coverage by 10 % will increase the expected deleterious homozygote numbers in ROH regions by 157 and decrease the expected number of deleterious homozygotes in non-ROH regions by 10, yielding an expected net increase of 147 deleterious homozygotes.Fig. 3

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