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Runs of homozygosity and distribution of functional variants in the cattle genome - PubMed

  • ️Thu Jan 01 2015

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

Qianqian Zhang et al. BMC Genomics. 2015.

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.

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Figures

Fig. 1
Fig. 1

ROH general statistics. a Average genome-wide nucleotide diversity (polymorphic sites per 10,000 bp); b Average nucleotide diversity outside ROH (polymorphic sites per 10,000 bp); c Average ROH size (bp); d Average genome-wide ROH totals

Fig 2
Fig 2

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

Fig. 3
Fig. 3

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

Fig. 4
Fig. 4

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

Fig. 5
Fig. 5

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

Fig. 6
Fig. 6

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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