pubmed.ncbi.nlm.nih.gov

Regions of homozygosity in the porcine genome: consequence of demography and the recombination landscape - PubMed

Regions of homozygosity in the porcine genome: consequence of demography and the recombination landscape

Mirte Bosse et al. PLoS Genet. 2012.

Abstract

Inbreeding has long been recognized as a primary cause of fitness reduction in both wild and domesticated populations. Consanguineous matings cause inheritance of haplotypes that are identical by descent (IBD) and result in homozygous stretches along the genome of the offspring. Size and position of regions of homozygosity (ROHs) are expected to correlate with genomic features such as GC content and recombination rate, but also direction of selection. Thus, ROHs should be non-randomly distributed across the genome. Therefore, demographic history may not fully predict the effects of inbreeding. The porcine genome has a relatively heterogeneous distribution of recombination rate, making Sus scrofa an excellent model to study the influence of both recombination landscape and demography on genomic variation. This study utilizes next-generation sequencing data for the analysis of genomic ROH patterns, using a comparative sliding window approach. We present an in-depth study of genomic variation based on three different parameters: nucleotide diversity outside ROHs, the number of ROHs in the genome, and the average ROH size. We identified an abundance of ROHs in all genomes of multiple pigs from commercial breeds and wild populations from Eurasia. Size and number of ROHs are in agreement with known demography of the populations, with population bottlenecks highly increasing ROH occurrence. Nucleotide diversity outside ROHs is high in populations derived from a large ancient population, regardless of current population size. In addition, we show an unequal genomic ROH distribution, with strong correlations of ROH size and abundance with recombination rate and GC content. Global gene content does not correlate with ROH frequency, but some ROH hotspots do contain positive selected genes in commercial lines and wild populations. This study highlights the importance of the influence of demography and recombination on homozygosity in the genome to understand the effects of inbreeding.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Summary statistics for genomic variation.

The distributions of ROH statistics for Asian breeds (n = 7), Asian wild boars(n = 5), European breeds (n = 29), European wild boars (n = 6) and other species (n = 5). Groups are divided based on geography (Asians and Europeans), domestication (pigs and wild boars) and speciation (Other-species include the African Warthog Phacochoerus africanus and other representatives of the Sus genus being Sus barbatus, Sus celebensis, Sus verrucosus and Sus cebifrons). Values are averaged within individuals resulting in a single data point per ROH characteristic for each individual. 1A. nucleotide diversity including ROHs (*10−4 bp) 1B. nucleotide diversity excluding ROHs (*10−4 bp) 1C. Average ROH size (*104 bp) 1D. number of ROHs in the genomes of individuals.

Figure 2
Figure 2. Total number of ROHs and proportion of the genome covered by ROHs.

2A. The average number of ROHs belonging to three size classes small (<100 Kbp) medium (0.1 to 5 Mbp) and large (>5 Mbp) for each of the different groups. 2B. The total size of the genome that is covered by the particular ROH size class in one individual, averaged per group. The Japanese wild boar is shown separately and is not included in the Asian group, as its demographic history from an island population and the associated ROH pattern is very distinct from all other sampled individuals. Asian wild boars (n = 4), Asian pigs (n = 7), European wild boars (n = 6), European pigs (n = 29), other species (n = 5).

Figure 3
Figure 3. ROH size in pigs based on the 60K chip method and the re-sequencing method.

3A shows the correlation between both methods when the total sum of ROHs is taken from the re-sequencing method (‘Genomic ROHsum’) and the 60K chip method (‘60K ROHsum’). In 3B the correlation is shown when only the ROHs over 5 Mbp are taken into account for the re-sequencing method. The outlier for the Asian group (the Japanese wild boar) is not included in the R2 calculations.

Figure 4
Figure 4. Number and cumulative ROH size (ROHs>5MB) for all genotyped individuals.

Number of ROHs and sum of ROHs detected by PLINK for all 241 individuals genotyped by the Illumina porcine 60k beadchip. Sum of ROHsize is *1000 bp. 4A. ROHs in domesticated individuals. Asian pigs are shown in red, orange and purple and the European pigs are in blue and green. 4B. ROHs in wild individuals. Asian wild boars are shown in red and orange and the European wild populations are displayed in green and blue. The dashed line represents the range of ROH number and ROH size for the domesticated individuals. The individuals marked with * are putative hybrids.

Figure 5
Figure 5. Three-point ROH statistics for all 52 sequenced individuals.

On the x-axis, the number of ROHs in the genome per individual is plotted, the average ROH size (*104 bp) is displayed on the y-axis and the nucleotide diversity outside ROHs in a 10 kb window ‘nucleotide diversity (π-out *10−4)’ on the z-axis. Coloration is based on relatedness and geography, with individuals from the same populations having the same color.

Figure 6
Figure 6. Characteristics of the porcine genome over relative chromosomal position.

Physical distribution of total nucleotide diversity (6A), nucleotide diversity outside ROHs (6B), GC content (6C), recombination rate (6D) over chromosomes. Relative chromosomal position is averaged for all chromosomes so that 0.0 represents the left telomeric region and 1.0 the far right telomere.

Figure 7
Figure 7. Distribution of ROHs over relative chromosomal position.

ROHs were split into three size classes; big (x>5 Mbp), medium (0.1 to 5 Mbp) and small (x<0.1 Mbp). The distribution is relative only to the total number of ROH bins in that particular size class, and the distributions are averaged over all chromosomes. ROH distribution is given for four groups: European pigs (7A), European wild boars (7B), Asian pigs (7C) and Asian wild boars (including the Japanese, 7D).

Similar articles

Cited by

References

    1. Auton A, Bryc K, Boyko AR, Lohmueller KE, Novembre J, et al. (2009) Global distribution of genomic diversity underscores rich complex history of continental human populations. Genome Res 19: 795–803. - PMC - PubMed
    1. vonHoldt BM, Pollinger JP, Earl DA, Knowles JC, Boyko AR, et al. (2011) A genome-wide perspective on the evolutionary history of enigmatic wolf-like canids. Genome Res 21: 1294–1305. - PMC - PubMed
    1. Ku CS, Naidoo N, Teo SM, Pawitan Y (2011) Regions of homozygosity and their impact on complex diseases and traits. Hum Genet 129: 1–15. - PubMed
    1. Nalls MA, Guerreiro RJ, Simon-Sanchez J, Bras JT, Traynor BJ, et al. (2009) Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer's disease. Neurogenetics 10: 183–190. - PMC - PubMed
    1. Vine AE, McQuillin A, Bass NJ, Pereira A, Kandaswamy R, et al. (2009) No evidence for excess runs of homozygosity in bipolar disorder. Psychiatr Genet 19: 165–170. - PubMed

Publication types

MeSH terms