Genome-wide association tests of inversions with application to psoriasis

Ma, Jianchao; Xiong, Momiao; You, Ming; Lozano, Guillermina; Amos, Christopher I.

doi:10.1007/s00439-014-1437-1

Cited by 11 publications

(10 citation statements)

References 33 publications

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“…As a consequence, new mutations are not exchanged between the genomic segments of each orientation. The lack of recombination then increases genetic differentiation and leads to characteristic signatures on PCA plots (e.g., De Jong et al, 2012 ; Ma and Amos, 2012 ; Ma et al, 2014 ; Kemppainen et al, 2015 ) such as the ones we observed in some ROIs. Natural selection can also create extended haplotypes.…”

Section: Discussionmentioning

confidence: 67%

Population Genomic Analysis Reveals Differential Evolutionary Histories and Patterns of Diversity across Subgenomes and Subpopulations of Brassica napus L.

et al. 2016

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The allotetraploid species Brassica napus L. is a global crop of major economic importance, providing canola oil (seed) and vegetables for human consumption and fodder and meal for livestock feed. Characterizing the genetic diversity present in the extant germplasm pool of B. napus is fundamental to better conserve, manage and utilize the genetic resources of this species. We used sequence-based genotyping to identify and genotype 30,881 SNPs in a diversity panel of 782 B. napus accessions, representing samples of winter and spring growth habits originating from 33 countries across Europe, Asia, and America. We detected strong population structure broadly concordant with growth habit and geography, and identified three major genetic groups: spring (SP), winter Europe (WE), and winter Asia (WA). Subpopulation-specific polymorphism patterns suggest enriched genetic diversity within the WA group and a smaller effective breeding population for the SP group compared to WE. Interestingly, the two subgenomes of B. napus appear to have different geographic origins, with phylogenetic analysis placing WE and WA as basal clades for the other subpopulations in the C and A subgenomes, respectively. Finally, we identified 16 genomic regions where the patterns of diversity differed markedly from the genome-wide average, several of which are suggestive of genomic inversions. The results obtained in this study constitute a valuable resource for worldwide breeding efforts and the genetic dissection and prediction of complex B. napus traits.

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Section: Discussionmentioning

confidence: 67%

Population Genomic Analysis Reveals Differential Evolutionary Histories and Patterns of Diversity across Subgenomes and Subpopulations of Brassica napus L.

et al. 2016

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“…In addition, Ma et al . [ 86 ] incorporated the inversions predicted with their principal components analysis-based approach from SNP data [ 43 ] in a GWAS analysis to find association of these regions with psoriasis, a chronic, inflammatory skin disease affecting 2–3% of the world population. They found significant associations of this disease with several candidate inversions, of which only two replicated in two different data sets.…”

Section: Polymorphic Inversions Associated To Phenotypes or Diseasesmentioning

confidence: 99%

“…It turns out that neither of the two candidate inversions overlaps those reported in the InvFEST database [ 39 ]. Therefore, these results should be taken cautiously given that the SNP signatures found might not be owing to an inversion, although the regions detected by the association test may still shed light on the genetic architecture of the disease, as the authors point out [ 86 ].…”

Section: Polymorphic Inversions Associated To Phenotypes or Diseasesmentioning

confidence: 99%

Human inversions and their functional consequences

Puig¹,

Casillas²,

Villatoro³

et al. 2015

Briefings in Functional Genomics

114

112

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Polymorphic inversions are a type of structural variants that are difficult to analyze owing to their balanced nature and the location of breakpoints within complex repeated regions. So far, only a handful of inversions have been studied in detail in humans and current knowledge about their possible functional effects is still limited. However, inversions have been related to phenotypic changes and adaptation in multiple species. In this review, we summarize the evidences of the functional impact of inversions in the human genome. First, given that inversions have been shown to inhibit recombination in heterokaryotes, chromosomes displaying different orientation are expected to evolve independently and this may lead to distinct gene-expression patterns. Second, inversions have a role as disease-causing mutations both by directly affecting gene structure or regulation in different ways, and by predisposing to other secondary arrangements in the offspring of inversion carriers. Finally, several inversions show signals of being selected during human evolution. These findings illustrate the potential of inversions to have phenotypic consequences also in humans and emphasize the importance of their inclusion in genome-wide association studies.

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“…In summary, not all PCs identify inversions when confounding factors are present. This will affect methods based purely on cluster structure in PCA projection (e.g., Ma et al (2014); Cáceres and González (2015))); by using association tests and Manhattan plots, our proposed framework is able to distinguish between PCs capturing inversions versus others. This is expected given the role of PCA in population inference and other tasks (Lee et al (2009); Patterson et al (2006); Price et al (2006); Neafsey et al (2010)).…”

Section: Discussionmentioning

confidence: 99%

“…Inversion differences within a population can also appear as clusters in PCA projections (Ma and Amos (2012); Ma et al (2014)), which has motivated computational detection based on characterizing this observed cluster structure (Cáceres and González (2015)). Because not all data induce a clear pattern in PCA projection plots, we were motivated to develop an alternative method based on single-SNP association tests (see Nowling and Emrich (2018c)).…”

Section: Introductionmentioning

confidence: 99%

Detecting Inversions with PCA in the Presence of Population Structure

Nowling

Manke

Emrich

2019

Preprint

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9Chromosomal inversions are associated with reproductive isolation and adaptation in insects such as Drosophila melanogaster and the malaria vectors Anopheles gambiae and Anopheles coluzzii. While methods based on read alignment have been useful in humans for detecting inversions, these methods are less successful in insects due to long repeated sequences at the breakpoints. Alternatively, inversions can be detected using principal component analysis (PCA) of single nucleotide polymorphisms (SNPs). We apply PCA-based inversion detection to a simulated data set and real data from multiple insect species, which vary in complexity from a single inversion in samples drawn from a single population to analyzing multiple overlapping inversions occurring in closely-related species, samples of which that were generated from multiple geographic locations. We show empirically that proper analysis of these data can be challenging when multiple inversions or populations are present, and that our alternative framework is more robust in these more difficult scenarios. 10 11 12 13 14 15 16 17 18 19 20 21 Chromosomal inversions play an important role in ecological adaptation by enabling the accumulation 22 of beneficial alleles (Love et al. (2016); Fuller et al. (2018); Prevosti et al. (1988)) and reproductive 23 isolation (Noor et al. (2001)). For example, the 2La inversion in the Anopheles gambiae complex has 24 been associated with thermal tolerance of larvae (Rocca et al. (2009)), enhanced desiccation resistance in 25 adult mosquitoes (Gray et al. (2009)), and susceptibility to at least one species (Plasmodium falciparum) 26 of malaria (Riehle et al. (2017)). 27 Inversion analysis contains three sub-problems: detection (is an inversion present?), localization of an 28 inversion along a chromosome arm, and determining the orientations of inversions present in each sample 29 (karyotyping). Most techniques can perform a subset of these tasks, but not all of them. For example, 30 some insects such as Drosophila melanogaster and the mosquito Anopheles gambiae have large polytene 31 chromosomes, which can be seen directly under a microscope. This enables detection and karyotyping of 32 previously characterized inversions (Lobo et al. (2010); Sharakhov et al. (2006); George et al. (2010)). 33 Computational approaches developed for model organisms such as human -or species without visible 34 chromosomes including many other insects -are generally based on sequencing large DNA fragments 35 from alternative karyotypes. Specifically, inversion breakpoints relative to a known reference genome can 36 discovered by checking for cases where either mate-pair or long-read sequence data align unexpectedly 37 (e.g., Zhu et al. (2017); Corbett-Detig et al. (2012); Hormozdiari et al. (2009); Chen et al. (2009); Suzuki 38 et al. (2014); Zhu et al. (2018)). Breakpoints in Anopheles mosquitoes are characterized by long, repeated 39 sequences (Sharakhov et al. (2006); Lobo et al. ( 2010)), however, which has prohibited break point 40 detection using ...

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Genome-wide association tests of inversions with application to psoriasis

Cited by 11 publications

References 33 publications

Population Genomic Analysis Reveals Differential Evolutionary Histories and Patterns of Diversity across Subgenomes and Subpopulations of Brassica napus L.

Population Genomic Analysis Reveals Differential Evolutionary Histories and Patterns of Diversity across Subgenomes and Subpopulations of Brassica napus L.

Human inversions and their functional consequences

Detecting Inversions with PCA in the Presence of Population Structure

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