Genomic Rearrangements inArabidopsisConsidered as Quantitative Traits.
To understand the population genetics of structural variants and their effects on phenotypes, we developed an approach to mapping structural variants that segregate in a population sequenced at low coverage. We avoid calling structural variants directly. Instead, the evidence for a potential structural variant at a locus is indicated by variation in the counts of short-reads that map anomalously to that locus. These structural variant traits are treated as quantitative traits and mapped genetically, analogously to a gene expression study. Association between a structural variant trait at one locus, and genotypes at a distant locus indicate the origin and target of a transposition. Using ultra-low-coverage (0.3×) population sequence data from 488 recombinant inbredArabidopsis thalianagenomes, we identified 6502 segregating structural variants. Remarkably, 25% of these were transpositions. While many structural variants cannot be delineated precisely, we validated 83% of 44 predicted transposition breakpoints by polymerase chain reaction. We show that specific structural variants may be causative for quantitative trait loci for germination and resistance to infection by the fungusAlbugo laibachii, isolate Nc14. Further we show that the phenotypic heritability attributable to read-mapping anomalies differs from, and, in the case of time to germination and bolting, exceeds that due to standard genetic variation. Genes within structural variants are also more likely to be silenced or dysregulated. This approach complements the prevalent strategy of structural variant discovery in fewer individuals sequenced at high coverage. It is generally applicable to large populations sequenced at low-coverage, and is particularly suited to mapping transpositions.
Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, United Kingdom.|Department of Statistics, University of Oxford, OX1 3TG, United Kingdom.
Martha
M
Imprialou
Department of Computer Science, Swiss Federal Institute of Technology in Zurich, 8092, Switzerland.
André
0000-0002-3411-0692
A
Kahles
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840.
Joshua G
JG
Steffen
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840.
Edward J
EJ
Osborne
Department of Comparative Development and Genetics, Max Planck Institute for Plant Breeding Research, 50829 Köln, Germany.
Xiangchao
0000-0001-6398-5191
X
Gan
Department of Comparative Development and Genetics, Max Planck Institute for Plant Breeding Research, 50829 Köln, Germany.
Janne
J
Lempe
Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, United Kingdom.
Amarjit
A
Bhomra
Department of Plant Sciences, University of Oxford, OX1 3RB, United Kingdom.
Eric
E
Belfield
Department of Plant Sciences, University of Oxford, OX1 3RB, United Kingdom.|Department of Comparative Plant and Fungal Biology, Royal Botanic Gardens Kew, Ardingly RH17 6TN, United Kingdom.
Anne
A
Visscher
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840.
Robert
R
Greenhalgh
Department of Plant Sciences, University of Oxford, OX1 3RB, United Kingdom.
Nicholas P
NP
Harberd
John Innes Centre, Norwich NR4 7UH, United Kingdom.
Richard
R
Goram
Department of Statistics, University of Oxford, OX1 3TG, United Kingdom.
Jotun
0000-0002-8100-0824
J
Hein
UMR INRA-Agrocampus Ouest-Université de Rennes 1, 35653 Le Rheu Cedex, France.
Alexandre
A
Robert-Seilaniantz
The Sainsbury Laboratory, Norwich Research Park, NR4 7UH, United Kingdom.
Jonathan
0000-0002-4953-261X
J
Jones
European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, United Kingdom.
Oliver
0000-0002-8818-7193
O
Stegle
Department of Biology and Biochemistry, University of Bath, BA2 7AY, United Kingdom.
Paula
P
Kover
Department of Comparative Development and Genetics, Max Planck Institute for Plant Breeding Research, 50829 Köln, Germany.
Miltos
M
Tsiantis
Department of Population Genetics, Gregor Mendel Institute of Molecular Plant Biology, 1030 Vienna, Austria.
Magnus
0000-0001-7178-9748
M
Nordborg
Department of Computer Science, Swiss Federal Institute of Technology in Zurich, 8092, Switzerland.
Gunnar
0000-0001-5486-8532
G
Rätsch
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840.|Center for Cell and Genome Science, University of Utah, Salt Lake City, Utah 84112-0840.
Richard M
0000-0002-1470-301X
RM
Clark
UCL Genetics Institute, University College London, WC1 6BT, United Kingdom r.mott@ucl.ac.uk.
Richard
0000-0002-1022-9330
R
Mott
D017360:Arabidopsis / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D056914:Genomic Structural Variation; D010641:Phenotype; D057865:Plant Immunity / Q000235:genetics; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable
Arabidopsis; heritability; low-coverage sequencing; quantitative trait locus; structural variation