TY - JOUR
T1 - Genomic rearrangements in Arabidopsis considered as quantitative traits
AU - Imprialou, Martha
AU - Kahles, André
AU - Steffen, Joshua G.
AU - Osborne, Edward J.
AU - Gan, Xiangchao
AU - Lempe, Janne
AU - Bhomra, Amarjit
AU - Belfield, Eric J.
AU - Visscher, Anne
AU - Greenhalgh, Robert
AU - Harberd, Nicholas P.
AU - Goram, Richard
AU - Hein, Jotun
AU - Robert-Seilaniantz, Alexandre
AU - Jones, Jonathan D G
AU - Stegle, Oliver
AU - Kover, Paula
AU - Tsiantis, Miltos
AU - Nordborg, Magnus
AU - Rätsch, Gunnar
AU - Clark, Richard M.
AU - Mott, Richard
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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 (0.33) population sequence data from 488 recombinant inbred Arabidopsis thaliana genomes, 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 fungus Albugo 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 lowcoverage, and is particularly suited to mapping transpositions.
AB - 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 (0.33) population sequence data from 488 recombinant inbred Arabidopsis thaliana genomes, 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 fungus Albugo 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 lowcoverage, and is particularly suited to mapping transpositions.
KW - Arabidopsis
KW - Heritability
KW - Low-coverage sequencing
KW - Quantitative trait locus
KW - Structural variation
UR - http://www.scopus.com/inward/record.url?scp=85017208182&partnerID=8YFLogxK
UR - https://doi.org/10.1534/genetics.116.192823
U2 - 10.1534/genetics.116.192823
DO - 10.1534/genetics.116.192823
M3 - Article
AN - SCOPUS:85017208182
SN - 0016-6731
VL - 205
SP - 1425
EP - 1441
JO - Genetics
JF - Genetics
IS - 4
ER -