Vitamin D-related genes, blood vitamin D levels and colorectal cancer risk in western european populations
Fedirko, Veronika ; Mandle, Hannah B. ; Zhu, Wanzhe ; Hughes, David J. ; Siddiq, Afshan ; Ferrari, Pietro ; Romieu, Isabelle ; Riboli, Elio ; Bueno-de-Mesquita, Bas ; Duijnhoven, Fränzel J.B. Van; Siersema, Peter D. ; Tjønneland, Anne ; Olsen, Anja ; Perduca, Vittorio ; Carbonnel, Franck ; Boutron-Ruault, Marie Christine ; Kühn, Tilman ; Johnson, Theron ; Krasimira, Aleksandrova ; Trichopoulou, Antonia ; Makrythanasis, Periklis ; Thanos, Dimitris ; Panico, Salvatore ; Krogh, Vittorio ; Sacerdote, Carlotta ; Skeie, Guri ; Weiderpass, Elisabete ; Colorado-Yohar, Sandra ; Sala, Núria ; Barricarte, Aurelio ; Sanchez, Maria Jose ; Quirós, Ramón ; Amiano, Pilar ; Gylling, Björn ; Harlid, Sophia ; Perez-Cornago, Aurora ; Heath, Alicia K. ; Tsilidis, Konstantinos K. ; Aune, Dagfinn ; Freisling, Heinz ; Murphy, Neil ; Gunter, Marc J. ; Jenab, Mazda - \ 2019
Nutrients 11 (2019)8. - ISSN 2072-6643
Colorectal neoplasms - Incidence - Single nucleotide polymorphism (SNP) - Vitamin D
Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β(TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.
Genome-wide association mapping of flowering and ripening periods in apple
Urrestarazu, Jorge ; Muranty, Hélène ; Denancé, Caroline ; Leforestier, Diane ; Ravon, Elisa ; Guyader, Arnaud ; Guisnel, Rémi ; Feugey, Laurence ; Aubourg, Sébastien ; Celton, Jean Marc ; Daccord, Nicolas ; Dondini, Luca ; Gregori, Roberto ; Lateur, Marc ; Houben, Patrick ; Ordidge, Matthew ; Paprstein, Frantisek ; Sedlak, Jiri ; Nybom, Hilde ; Garkava-Gustavsson, Larisa ; Troggio, Michela ; Bianco, Luca ; Velasco, Riccardo ; Poncet, Charles ; Théron, Anthony ; Moriya, Shigeki ; Bink, Marco C.A.M. ; Laurens, François ; Tartarini, Stefano ; Durel, Charles Eric - \ 2017
Frontiers in Plant Science 8 (2017). - ISSN 1664-462X
Adaptive traits - Association genetics - Germplasm collection - GWAS - Malus × domestica Borkh - Microsynteny - Quantitative trait loci - SNP
Deciphering the genetic control of flowering and ripening periods in apple is essential for breeding cultivars adapted to their growing environments. We implemented a large Genome-Wide Association Study (GWAS) at the European level using an association panel of 1,168 different apple genotypes distributed over six locations and phenotyped for these phenological traits. The panel was genotyped at a high-density of SNPs using the Axiom®Apple 480 K SNP array. We ran GWAS with a multi-locus mixed model (MLMM), which handles the putatively confounding effect of significant SNPs elsewhere on the genome. Genomic regions were further investigated to reveal candidate genes responsible for the phenotypic variation. At the whole population level, GWAS retained two SNPs as cofactors on chromosome 9 for flowering period, and six for ripening period (four on chromosome 3, one on chromosome 10 and one on chromosome 16) which, together accounted for 8.9 and 17.2% of the phenotypic variance, respectively. For both traits, SNPs in weak linkage disequilibrium were detected nearby, thus suggesting the existence of allelic heterogeneity. The geographic origins and relationships of apple cultivars accounted for large parts of the phenotypic variation. Variation in genotypic frequency of the SNPs associated with the two traits was connected to the geographic origin of the genotypes (grouped as North+East, West and South Europe), and indicated differential selection in different growing environments. Genes encoding transcription factors containing either NAC or MADS domains were identified as major candidates within the small confidence intervals computed for the associated genomic regions. A strong microsynteny between apple and peach was revealed in all the four confidence interval regions. This study shows how association genetics can unravel the genetic control of important horticultural traits in apple, as well as reduce the confidence intervals of the associated regions identified by linkage mapping approaches. Our findings can be used for the improvement of apple through marker-assisted breeding strategies that take advantage of the accumulating additive effects of the identified SNPs.
Genome wide association study of two phenology traits (flowering time and maturity date) in apple
Muranty, Hélène ; Urrestarazu, J. ; Denancé, C. ; Leforestier, D. ; Ravon, E. ; Guyader, A. ; Guisnel, R. ; Feugey, L. ; Tartarini, S. ; Dondini, L. ; Gregori, R. ; Lateur, M. ; Houben, E.H.P. ; Sedlak, J. ; Paprstein, F. ; Ordidge, M. ; Nybom, H. ; Garkava-Gustavsson, L. ; Troggio, M. ; Bianco, L. ; Velasco, R. ; Poncet, C. ; Théron, Anthony ; Bink, M.C.A.M. ; Laurens, F. ; Durel, C.E. - \ 2017
In: 14th EUCARPIA Symposium on Fruit Breeding and Genetics International Society for Horticultural Science (Acta Horticulturae ) - ISBN 9789462611689 - p. 411 - 417.
Germplasm collections - Malus × domestica - Marker-assisted selection
The aim of Genome Wide Association Studies (GWAS) is to identify markers in tight linkage disequilibrium with loci controlling quantitative trait variation. These markers can then be used in marker-assisted selection (MAS) in fruit crops such as apple. The GWAS approach involves both phenotyping of a large population of mostly unrelated individuals for the traits of interest, and genotyping at high marker density. In the EU-FP7 project FruitBreedomics, almost 1,200 European diploid dessert apple accessions (old and/or local cultivars) from six germplasm collections were genotyped with the Affymetrix Axiom-Apple480K array (487,000 SNPs). Phenotypic data on a large number of traits have been gathered during the project. Here we focus on flowering period and harvesting date. Knowledge of the genetic control of these traits is necessary to develop cultivars that can face the challenges imposed by global climate change and to target cultivar development as a function of a prolonged vegetation period in the production regions. Different models were tested, including control for effects of population structure and relatedness between cultivars. The full model, controlling for both structure and relatedness, was shown to be the most appropriate to avoid spurious marker-trait associations. When analyzing data over all collections, one significant marker-trait association was obtained for each trait, on chromosomes 9 and 3, for flowering period and harvesting date, respectively. Thereby, genomic locations previously identified in bi-parental populations could now be confirmed for a genetically diverse germplasm.
Development and validation of the Axiom®Apple480K SNP genotyping array
Bianco, Luca ; Cestaro, Alessandro ; Linsmith, Gareth ; Muranty, Hélène ; Denancé, Caroline ; Théron, Anthony ; Poncet, Charles ; Micheletti, Diego ; Kerschbamer, Emanuela ; Pierro, Erica A. Di; Larger, Simone ; Pindo, Massimo ; De Weg, Eric Van; Davassi, Alessandro ; Laurens, François ; Velasco, Riccardo ; Durel, Charles Eric ; Troggio, Michela - \ 2016
The Plant Journal 86 (2016)1. - ISSN 0960-7412 - p. 62 - 74.
genome-wide association study - genotyping - linkage mapping - Malus × domestica Borkh. - SNP chip - validation
Cultivated apple (Malus × domestica Borkh.) is one of the most important fruit crops in temperate regions, and has great economic and cultural value. The apple genome is highly heterozygous and has undergone a recent duplication which, combined with a rapid linkage disequilibrium decay, makes it difficult to perform genome-wide association (GWA) studies. Single nucleotide polymorphism arrays offer highly multiplexed assays at a relatively low cost per data point and can be a valid tool for the identification of the markers associated with traits of interest. Here, we describe the development and validation of a 487K SNP Affymetrix Axiom® genotyping array for apple and discuss its potential applications. The array has been built from the high-depth resequencing of 63 different cultivars covering most of the genetic diversity in cultivated apple. The SNPs were chosen by applying a focal points approach to enrich genic regions, but also to reach a uniform coverage of non-genic regions. A total of 1324 apple accessions, including the 92 progenies of two mapping populations, have been genotyped with the Axiom®Apple480K to assess the effectiveness of the array. A large majority of SNPs (359 994 or 74%) fell in the stringent class of poly high resolution polymorphisms. We also devised a filtering procedure to identify a subset of 275K very robust markers that can be safely used for germplasm surveys in apple. The Axiom®Apple480K has now been commercially released both for public and proprietary use and will likely be a reference tool for GWA studies in apple.
Selection of Prunus spinosa as a dwarfing rootstock for high density plum orchards
Maas, F.M. ; Balkhoven-Baart, J.M.T. ; Steeg, P.A.H. van der - \ 2014
In: X International Symposium on Integrating Canopy, Rootstock and Environmental Physiology in Orchard Systems. - Leuven : ISHS - ISBN 9789462610484 - p. 507 - 516.
In 1987 a selection program was started to find a dwarfing rootstock for European plums. Prunus spinosa (blackthorn) was the chosen species due to its winter hardiness, drought tolerance and previously shown compatibility with plum. In 1990 about 1000 blackthorn seedlings were budded with ‘Opal’ plum. Based on the vigour of the trees during the first year in the nursery, 113 selections were selected for further testing for their effect on tree development and fruit production. The amount of root suckers and thorns were used as additional selection criteria. In 1999 the number of selections was reduced to 24. In several trials carried out between 2006 and 2011, the vigour and yield of ‘Victoria’ on these selections was shown to vary between that on the commonly used rootstock ‘Saint Julien A’ and ‘Krymsk1’ (VVA-1), a dwarfing and highly productive rootstock that had been introduced in the Netherlands concurrently with the trials. Although ‘Krymsk11’ gives very good tree-size control and precocity, it is too dwarfing for some soils and cultivars and sensitive to bacterial canker caused by Pseudomomas syringae. Recently, the five most promising selections were planted in higher numbers. The best selection will be released as soon as it has been registered, and virus free material becomes available. Additional tests will be needed to determine the suitability of these blackthorn selections for other stone fruit species like peach and apricot and for other soils and climatic conditions.
Evaluation of KrymskReg.5 (VSL-2) and KrymskReg.6 (LC-52) as rootstocks for sweet cherry 'Kordia'
Maas, F.M. ; Balkhoven-Baart, J.M.T. ; Steeg, P.A.H. van der - \ 2014
In: X International Symposium on Integrating Canopy, Rootstock and Environmental Physiology in Orchard Systems. - Leuven : ISHS - p. 531 - 536.
During a 6-year period the growth and production of trees of sweet cherry ‘Kordia’ grafted on rootstocks Krymsk®5 (VSL-2), Krymsk®6 (LC-52) and GiSelA 5 were compared. Shoot growth, increase in trunk diameter and intensity of flowering of ‘Kordia’ were almost similar on all three stocks. Fruit production per tree was significantly higher for ‘Kordia’ on rootstocks Krymsk®6 and GiSelA 5, while that on Krymsk®5 was similar to that on GiSelA 5. Both Krymsk rootstocks gave a small reduction in fruit size, and a slightly lower sugar and acid content. With Krymsk®6, smaller fruit size was related to the higher fruit load of the trees and may be avoided by thinning the tree to the optimum crop load. With Krymsk®5, the reduction in fruit size could not be attributed to overcropping. Fruit cracking, a big problem for cherry growers in areas with high risks of rain in the harvest period, occurred less on Krymsk®6 than on GiSelA 5 or Krymsk®5. Both Krymsk rootstocks produced significantly more root suckers than GiSelA 5. The highest numbers were observed for Krymsk®5, which produced on average 3.3 suckers per tree per during the first 6 years in the orchard. Krymsk®5 also developed burrknots. From this trial it is concluded that Krymsk®6 can be a good alternative rootstock to GiSelA 5, especially for less well drained soils and because its effect on reducing the occurrence of fruit cracking. However, because of its tendency to reduce fruit size, overcropping should be prevented. Therefore, Krymsk®6 is probably less suited for self-compatible cultivars than for cultivars setting fruit only after cross pollination.