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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

Total ROH number and genome proportions. a The average small (< 100 kbp, Red), medium (0.1 to 3 Mbp, Green), and large (> 3 Mbp, Blue) ROH numbers for the four breeds; b Average total genome ROH coverage for a given size class within each breed
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Fig2: Total ROH number and genome proportions. a The average small (< 100 kbp, Red), medium (0.1 to 3 Mbp, Green), and large (> 3 Mbp, Blue) ROH numbers for the four breeds; b Average total genome ROH coverage for a given size class within each breed

Mentions: ROH were separated into three size classes: small (10 kbp to 100 kbp), medium (0.1 to 3 Mbp), and large (> 3 Mbp) (as described in the Materials and Methods section). The proportion of ROH in each size class was computed in all 104 sequenced individuals. While small ROH were frequent throughout the genome, they constituted a small proportion of the entire genome (Fig. 2). In contrast, medium ROH were much less frequent, they constituted significantly more of the genome than either small or large ROH. Large ROH were at least tenfold less numerous than medium ROH, but nevertheless covered a sizable proportion of the total genome length. Old-RED cattle on average had the largest proportion of their genome in large ROH. New-RED cattle had fewer genomic ROH and a smaller genomic proportion of ROH than HOL and JER cattle (P < 0.001). Old-RED and JER cattle on average had more ROH and increased proportion of genomic homozygosity.Fig 2


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)

Total ROH number and genome proportions. a The average small (< 100 kbp, Red), medium (0.1 to 3 Mbp, Green), and large (> 3 Mbp, Blue) ROH numbers for the four breeds; b Average total genome ROH coverage for a given size class within each breed
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Total ROH number and genome proportions. a The average small (< 100 kbp, Red), medium (0.1 to 3 Mbp, Green), and large (> 3 Mbp, Blue) ROH numbers for the four breeds; b Average total genome ROH coverage for a given size class within each breed
Mentions: ROH were separated into three size classes: small (10 kbp to 100 kbp), medium (0.1 to 3 Mbp), and large (> 3 Mbp) (as described in the Materials and Methods section). The proportion of ROH in each size class was computed in all 104 sequenced individuals. While small ROH were frequent throughout the genome, they constituted a small proportion of the entire genome (Fig. 2). In contrast, medium ROH were much less frequent, they constituted significantly more of the genome than either small or large ROH. Large ROH were at least tenfold less numerous than medium ROH, but nevertheless covered a sizable proportion of the total genome length. Old-RED cattle on average had the largest proportion of their genome in large ROH. New-RED cattle had fewer genomic ROH and a smaller genomic proportion of ROH than HOL and JER cattle (P < 0.001). Old-RED and JER cattle on average had more ROH and increased proportion of genomic homozygosity.Fig 2

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