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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 versus the genome ROH coverage for each individual. a Any ROH region; b Short; c Medium; and d Long ROH regions. Red points represent deleterious homozygotes, and blue points represent non-deleterious homozygotes
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Fig4: The proportion of all genome-wide non-reference homozygotes falling in ROH regions versus the genome ROH coverage for each individual. a Any ROH region; b Short; c Medium; and d Long ROH regions. Red points represent deleterious homozygotes, and blue points represent non-deleterious homozygotes

Mentions: Figure 4a shows the proportion of deleterious non-reference homozygotes inside and outside ROH regions (fi,Rd and fi,Rn) versus total genomic ROH coverage (Gi,R). The proportions of non-deleterious and deleterious homozygous genotypes within ROH were strongly positively correlated with total genomic ROH coverage (Pearson r = 0.96 for non-deleterious and r = 0.99 for deleterious). These high correlations were expected, because as larger proportions of homozygous genotypes occur, ROH coverage in the genome increases, and therefore ROH comprise an increasingly greater proportion of the genome [24]. The fi,Rd proportion in genome-wide deleterious homozygotes within ROH consistently exceeded the fi,Rn proportion of genome-wide non-deleterious homozygotes within ROH and the increasing slopes differed between deleterious and non-deleterious variants.Fig. 4


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 versus the genome ROH coverage for each individual. a Any ROH region; b Short; c Medium; and d Long ROH regions. Red points represent deleterious homozygotes, and blue points represent non-deleterious homozygotes
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: The proportion of all genome-wide non-reference homozygotes falling in ROH regions versus the genome ROH coverage for each individual. a Any ROH region; b Short; c Medium; and d Long ROH regions. Red points represent deleterious homozygotes, and blue points represent non-deleterious homozygotes
Mentions: Figure 4a shows the proportion of deleterious non-reference homozygotes inside and outside ROH regions (fi,Rd and fi,Rn) versus total genomic ROH coverage (Gi,R). The proportions of non-deleterious and deleterious homozygous genotypes within ROH were strongly positively correlated with total genomic ROH coverage (Pearson r = 0.96 for non-deleterious and r = 0.99 for deleterious). These high correlations were expected, because as larger proportions of homozygous genotypes occur, ROH coverage in the genome increases, and therefore ROH comprise an increasingly greater proportion of the genome [24]. The fi,Rd proportion in genome-wide deleterious homozygotes within ROH consistently exceeded the fi,Rn proportion of genome-wide non-deleterious homozygotes within ROH and the increasing slopes differed between deleterious and non-deleterious variants.Fig. 4

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