How to study runs of homozygosity using PLINK? A guide for analyzing medium density SNP data in livestock and pet species

Meyermans, Roel; Gorssen, Wim; Buys, Nadine; Janssens, Steven

doi:10.1186/s12864-020-6463-x

Cited by 151 publications

(187 citation statements)

References 42 publications

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“…The Burmese cats in this study displayed high homozygosity and long ROH consistent with previous reports 14 . The distribution of ROH across the Burmese samples was consistent with previous results 39 . Long ROH (> 5 Mb) are indicative of recent inbreeding, unbroken by historical recombination events.…”

Section: Discussionsupporting

confidence: 91%

“…Therefore, for most populations, medium density genotyping arrays do not lend themselves to high resolution analysis of ROH 40 . For this analysis, minor allele frequency (MAF) and LD pruning were not employed in the ROH detection as both have been shown to mask the detection of true ROH by limiting genome coverage 39 . Long ROH (1-10 Mb) made up the largest size category observed across all populations, accounting for over 70% of ROH observations.…”

Section: Discussionmentioning

confidence: 99%

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Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus)

Samaha

Wade

Beatty

et al. 2020

Sci Rep

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Diabetes mellitus, a common endocrinopathy affecting domestic cats, shares many clinical and pathologic features with type 2 diabetes in humans. In Australia and Europe, diabetes mellitus is almost four times more common among Burmese cats than in other breeds. As a genetically isolated population, the diabetic Australian Burmese cat provides a spontaneous genetic model for studying diabetes mellitus in humans. Studying complex diseases in pedigreed breeds facilitates tighter control of confounding factors including population stratification, allelic frequencies and environmental heterogeneity. We used the feline SNV array and whole genome sequence data to undertake a genome wide-association study and runs of homozygosity analysis, of a case–control cohort of Australian and European Burmese cats. Our results identified diabetes-associated haplotypes across chromosomes A3, B1 and E1 and selective sweeps across the Burmese breed on chromosomes B1, B3, D1 and D4. The locus on chromosome B1, common to both analyses, revealed coding and splice region variants in candidate genes, ANK1, EPHX2 and LOX2, implicated in diabetes mellitus and lipid dysregulation. Mapping this condition in Burmese cats has revealed a polygenic spectrum, implicating loci linked to pancreatic beta cell dysfunction, lipid dysregulation and insulin resistance in the pathogenesis of diabetes mellitus in the Burmese cat.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus)

Samaha

Wade

Beatty

et al. 2020

Sci Rep

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“…Moreover, a previous simulation study has tested out ROH calling programs and optimal settings [6], the ROH calling methods and their settings are still challenging [9,46]. Moreover, to avoid bias and overestimation for ROH detection using PLINK, more options should be considered carefully according to the genome coverage and the density of SNPs array [51].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Assessment of Runs of Homozygosity in Chinese Wagyu Beef Cattle

Zhao

Zhang

Liu

et al. 2020

Animals

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Runs of homozygosity (ROH) are continuous homozygous regions that generally exist in the DNA sequence of diploid organisms. Identifications of ROH leading to reduction in performance can provide valuable insight into the genetic architecture of complex traits. Here, we evaluated genome-wide patterns of homozygosity and their association with important traits in Chinese Wagyu beef cattle. We identified a total of 29,271 ROH segments from 462 animals. Within each animal, an average number of ROH was 63.36 while an average length was 62.19 Mb. To evaluate the enrichment of ROH across genomes, we initially identified 280 ROH regions by merging ROH events across all individuals. Of these, nine regions containing 154 candidate genes, were significantly associated with six traits (body height, chest circumference, fat coverage, backfat thickness, ribeye area, and carcass length; p < 0.01). Moreover, we found 26 consensus ROH regions with frequencies exceeding 10%, and several regions overlapped with QTLs, which are associated with body weight, calving ease, and stillbirth. Among them, we observed 41 candidate genes, including BCKDHB, MAB21L1, SLC2A13, FGFR3, FGFRL1, CPLX1, CTNNA1, CORT, CTNNBIP1, and NMNAT1, which have been previously reported to be related to body conformation, meat quality, susceptibility, and reproductive traits. In summary, we assessed genome-wide autozygosity patterns and inbreeding levels in Chinese Wagyu beef cattle. Our study identified many candidate regions and genes overlapped with ROH for several important traits, which could be unitized to assist the design of a selection mating strategy in beef cattle.

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“…Thus, this approach can be used to estimate 'genomic' or 'realized' IBD. A drawback of this approach is that a set of criteria have to be predefined to identify segments [59][60][61].…”

Section: Segment-based Inbreeding and Kinshipmentioning

confidence: 99%

“…Third, to limit the number of false positive segments, many criteria can be used to define segments. In literature, a wide range of (rather arbitrary) settings is used and these settings are often poorly reported, making it almost impossible to compare results across studies [60]. Fourth, the segment-based approach is computationally intensive, since it requires scanning four combinations of homologous chromosomes for each pair of individuals.…”

Section: Which Matrix Should Be Used To Limit Inbreeding Depression?mentioning

confidence: 99%

Genomic characterization and conservation of genetic diversity in cattle

Doekes¹

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Genetic diversity in livestock populations is important, because it forms the basis for these populations to adapt to changing environments and human demands. Traditionally, livestock genetic diversity has been characterized and conserved with pedigree-based measures of inbreeding and kinship. Thanks to the increasing availability of genomic information, in particular single nucleotide polymorphism (SNP) data, we now have additional opportunities to better manage genetic diversity. In this thesis, I utilized SNP data to characterize and conserve genetic diversity in Dutch cattle, both in in situ populations and ex situ gene bank collections. The Holstein Friesian (HF) breed was the main breed of interest, because of its importance in the Dutch and global dairy cattle sector. First, it was demonstrated how changes in breeding practices in the past have been accompanied by changes in genetic diversity trends in the Dutch-Flemish HF breeding program. Among others, it was shown that the introduction of genomic selection has been accompanied by an increase in pedigree-based and SNP-based rates of inbreeding and kinship. Second, the negative effects of inbreeding on performance ("inbreeding depression") were quantified for yield, fertility and udder health traits of Dutch HF cows. It was shown that recent inbreeding may be more harmful than ancient inbreeding, although results were mixed. It was also shown that, based on SNP data, the negative effects of inbreeding are quite equally distributed across the genome and well captured by genome-wide homozygosity. Third, the value of the Dutch cattle gene bank collection was demonstrated. It was shown that old HF gene bank bulls can be used in the current or future HF breeding program to increase (or recover) genetic diversity, or to improve genetic merit given a certain level of diversity. It was also shown that Dutch native breeds in the gene bank collection harbor genetic diversity, both within and across breeds, although some breeds showed substantial overlap. Last, it was discussed how genomic information (in particular SNP data) can be used to maintain genetic diversity in livestock populations. Based on our current knowledge and the availability of SNP data, I recommend to limit the increase in SNP-by-SNP similarity (and, thus, homozygosity) while performing selection. For gene bank collections, I envision a transition towards bio-digital resource centers, in which large amounts of genomic and phenotypic data are stored in addition to physical germplasm material. Overall, the findings of this thesis improve our understanding of (conservation of) genetic diversity in livestock and, thereby, contribute to sustainable livestock production.

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How to study runs of homozygosity using PLINK? A guide for analyzing medium density SNP data in livestock and pet species

Cited by 151 publications

References 42 publications

Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus)

Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus)

Genome-Wide Assessment of Runs of Homozygosity in Chinese Wagyu Beef Cattle

Genomic characterization and conservation of genetic diversity in cattle

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