O emprego de \"Total Genome Scan\" em modelos genéticos de doenças complexas tem sido fundamental para seleção de regiões cromossômicas envolvidas com traços complexos. Em nosso laboratório, identificamos cinco regiões cromossômicas associadas ao traço quantitativo pressão arterial (BP-QTL) que explicam 43% da variação da pressão arterial numa progênie obtida a partir de animais espontaneamente hipertensos (SHR) e \"Brown Norway\" (BN). Os BP-QTLs foram, então, validados por desenvolvimento de linhagens congênicas, incluindo uma para o cromossomo 4 (SHR.BN4) cuja substituição das sequências SHR pelo do animal BN levou a redução da pressão arterial sistólica basal (~14 mm Hg). O objetivo deste trabalho foi identificar as variantes genéticas candidatas neste intervalo cromossômico com base em diferenças no padrão de expressão gênica e na presença de alterações genéticas não sinônimas \"missense\" ou em regiões regulatórias conservadas que possam estar envolvidas na gênese da hipertensão. Identificamos 533 genes com expressão renal, dentre os 682 do intervalo, sendo que 28 apresentaram padrão de expressão diferente entre amostras de animais adultos (congênico vs. SHR) e seis apresentaram alterações não sinônimas \"missense\". É importante salientar que dos genes diferentemente expressos, encontramos alterações estruturais em regiões conservadas com potencial de participar na regulação em 11. Em conjunto, utilizamos uma plataforma integrada para selecionar 34 genes candidatos no cromossomo 4, dos quais 17 genes serão priorizados, para ser investigados quanto sua contribuição na hipertensão arterial do SHR e na hipertensão primária humana / Total genome scan in genetic models of complex diseases have been instrumental to select candidate genes underlying complex traits. We previously mapped 5 blood pressure related quantitative trait loci (BP-QTLs) that explain about 43% of the BP variance in a progeny derived from Spontaneous Hypertensive Rat (SHR) and Brown Norway (BN) rats. The BP-QTLs were then validated by derivation of congenic strains, including one for chromosome 4 (SHR.BN4) in which a segment from BN replaced the SHR sequences reducing basal systolic BP (~14 mm Hg). The aim of this project is to identify the candidate genetic variants within the chromosome interval based on differences in renal gene expression patterns and structural changes in both non-synonymous missense or within adjacent regulatory sequences that may contribute to hypertension. We identified 533 genes with renal expression, out of 682 in the interval, in which 28 presented differences in expression pattern in adult samples (congenic vs. SHR) and six presented non-synonymous missense alterations. In addition, 11 out of 28 differentially expressed genes showed structural alterations in adjacent conserved regions that potentially contribute to gene regulation. Taken together, using the proposed combination of strategies, we selected 34 hypertensive candidate genes in chromosome 4, in which 17 will be prioritized, to be further explored to assess their contribution to hypertension in the SHR and to essential hypertension in humans

<p>This dissertation explains why behavioral genetic research can be better informed by using characteristics in the human iris as biomarkers for personality, and is divided into five parts. Part I gives an introduction to the classical twin method and an overview of the findings that have led most developmental researchers to recognize that the normal variation of personality depends on a complex interplay between genetic and environmental factors. Part II highlights empirical findings that during the last twenty years have gradually moved genetic and environmental theory and research to evolve toward one another, and also presents the theory of genetics and experience that currently is used to explain how the interplay between genes and the environment works. Part III explains why, from a developmental perspective, it is of interest to identify candidate genes for personality, and gives a brief overview of genes that have been associated with personality. Problems associated with genetic research on the molecular level and how these apply to personality are also highlighted. Part IV examines molecular research on the iris and the brain, which suggests that genes expressed in the iris could be associated with personality, and explains how the use of iris characteristics can increase power to test candidate genes for personality by taking advantage of the self-organizing properties of the nervous system. The empirical foundation for the questions posed in this dissertation and also the empirical results are presented here. Part V discusses the associations found between iris characteristics and personality, and exemplifies how iris characteristics can be used within the theoretical frameworks presented in parts I, II, III and IV. In other words, Part V explains how iris characteristics – in addition to identify as well as test candidate genes for personality – can be used to investigate how people’s experiences in themselves are influenced by genetic factors.</p>

In this thesis we have studied genetic elements potentially contributing to the pathophysiology of psychiatric disorders, focusing on different sources of human genome variability, including SNPs and CNVs, which can affect not only coding genes but also RNA regulatory elements, such as miRNAs. First, we have interrogated different candidate genes for psychiatric disorders overlapping with known CNVs, finding 14 different genes variable in copy number in psychiatric disorders but not in control individuals. Then, narrowing the analysis on mood disorders, we explored GSK3&#946; gene considering both SNPs and a partially overlapping CNV. The GSK3&#946; promoter and intron 1 region was found significantly associated with an earlier onset of the major depressive disorder. Finally, we have found evidence possibly pointing to a precise post-transcriptional regulation of circadian rhythms by miRNAs in mood disorder patients. Concretely, a variant in the precursor form of miR-182 could play an important role in fine-tuning its target sites involved in the control of sleep/wake cycles. Overall, we have provided evidence of different types of genome variation on neuronal genes or miRNA regulatory regions that can potentially contribute to the development of psychiatric disorders. / En aquesta tesi hem estudiat elements genètics que podrien contribuir potencialment en la fisiopatologia dels trastorns psiquiàtrics, centrant-nos en diferents fonts de variabilitat genòmica humana, incloent els SNPs i els CNVs, els quals poden afectar no només a gens codificants sinó també a elements reguladors, com els miRNAs. Primer, vam interrogar diferents gens candidats per trastorns psiquiàtrics solapats amb CNVs coneguts, trobant que 14 gens eren variables en el número de còpia en pacients però no en individus controls. Després, restringint l'anàlisi a trastorns afectius, vam explorar el gen GSK3&#946; considerant SNPs així com també un CNV que se solapa parcialment amb el gen. Vam trobar la regió del promotor i de l'intró 1 del gen GSK3&#946; associada de manera significativa amb una inferior edat d'inici del trastorn de depressió major. Finalment, hem trobat evidències que possiblement indiquen una precisa regulació post-transcriptional dels ritmes circadians per miRNAs en pacients amb trastorns afectius. Concretament, una variant en la forma precursora del miR-182 podria jugar un paper important en la fina regulació dels seus gens diana implicats en el control dels cicles de son i vigília. En general, hem aportat evidències de què diferents tipus de variació genòmica en gens neuronals o regions reguladores com els miRNAs podrien contribuir potencialment en el desenvolupament de trastorns psiquiàtrics.

This dissertation explains why behavioral genetic research can be better informed by using characteristics in the human iris as biomarkers for personality, and is divided into five parts. Part I gives an introduction to the classical twin method and an overview of the findings that have led most developmental researchers to recognize that the normal variation of personality depends on a complex interplay between genetic and environmental factors. Part II highlights empirical findings that during the last twenty years have gradually moved genetic and environmental theory and research to evolve toward one another, and also presents the theory of genetics and experience that currently is used to explain how the interplay between genes and the environment works. Part III explains why, from a developmental perspective, it is of interest to identify candidate genes for personality, and gives a brief overview of genes that have been associated with personality. Problems associated with genetic research on the molecular level and how these apply to personality are also highlighted. Part IV examines molecular research on the iris and the brain, which suggests that genes expressed in the iris could be associated with personality, and explains how the use of iris characteristics can increase power to test candidate genes for personality by taking advantage of the self-organizing properties of the nervous system. The empirical foundation for the questions posed in this dissertation and also the empirical results are presented here. Part V discusses the associations found between iris characteristics and personality, and exemplifies how iris characteristics can be used within the theoretical frameworks presented in parts I, II, III and IV. In other words, Part V explains how iris characteristics – in addition to identify as well as test candidate genes for personality – can be used to investigate how people’s experiences in themselves are influenced by genetic factors.

Made available in DSpace on 2016-06-02T20:20:30Z (GMT). No. of bitstreams: 1 3056.pdf: 1837497 bytes, checksum: cec4b528a2c534515e5a1880b1f0309d (MD5) Previous issue date: 2010-01-03 / Universidade Federal de Minas Gerais / The Canchim has been used in beef cattle as an alternative to production intensification. Canchim (5/8 Charolais + 3/8 Zebu) and MA (offspring of Charolais bulls and 1/2 Canchim + 1/2 Zebu cows) constitute a synthetic beef cattle breed which has a good growth potential and tropical adaptation but suboptimal fat deposition under pasture. Backfat thickness (BF), total fat amount and distribution of fat have a strong impact on carcass and meat quality in beef cattle. For this reason, research has been conducted to increase fat deposition in this breed, including the search for molecular markers to identify animals with high genetic potential for fat deposition. To incorporate molecular genetics into breeding programs in beef cattle, it is essential that the association between molecular markers and production traits is evaluated in the population in which they are to be used. There are reports of many candidate genes and chromosomal segments associated with variation in fat deposition in cattle. The objective of this study was to identify SNPs associated to backfat thickness in Canchim. To achieve this objective we searched for SNPs in development and differentiation enhancing factor 1 and insulin-like growth factor binding protein 3 genes, tested the association of SNPs in the insulin-like growth factor binding protein 3, peroxisome proliferative active receptor gamma coactivator 1A, proteasome 26S subunit ATPase 1, development and differentiation enhancing factor 1, corticotropin releasing hormone and fatty acid binding protein 4 genes with fat thickness in Canchim and MA beef cattle. We also analyzed the existence of genomic regions associated with backfat thickness in these populations using a 54 K chip in extreme phenotypes. From the associated regions we selected the ones of BTA14 to validate the association by analysis of haplotypes in the whole population. The SNPs analyzed in development and differentiation enhancing factor 1 and fatty acid binding protein 4 genes were associated with variation in backfat thickness, wereas no association was found for the SNPs of the insulin-like growth factor binding protein 3, peroxisome proliferative active receptor gamma coactivator 1A, proteasome 26S subunit ATPase 1 and corticotropin releasing hormone genes. Additionally, two chromosomal regions of BTA14 were associated with the trait in this work. / A raça Canchim tem sido utilizada na bovinocultura de corte como alternativa de intensificação de produção. Grupos genéticos Canchim (5/8 Charolês + 3/8 Zebu) e MA (descendentes de touros Charoleses e de 1/2 Canchim + 1/2 Zebu) constituem essa raça sintética, que tem bom potencial de crescimento e adaptação tropical, mas deposita pouca gordura quando alimentada à pasto. Espessura de gordura subcutânea, quantidade e distribuição de gordura total têm grande impacto sobre a qualidade da carne e carcaça em gado de corte. Por este motivo, pesquisas têm sido realizadas com o objetivo de aumentar a deposição de gordura nessa raça, incluindo a busca por marcadores moleculares que auxiliem a identificação de animais com maior potencial genético para deposição de gordura. Para que a genética molecular possa ser incorporada nos programas de melhoramento de bovinos de corte, é essencial que a associação entre marcadores moleculares e características de produção seja avaliada na população em que se deseja utilizá-los. Há relatos de muitos genes candidatos e segmentos cromossômicos associados com a variação da deposição de gordura em bovinos. O objetivo desse trabalho foi identificar SNPs associados à deposição de gordura em animais da raça Canchim criados à pasto. Para tanto, foram prospectados SNPs nos genes do fator de aumento de desenvolvimento e de diferenciação 1 e proteína ligante ao fator de crescimento semelhante à insulina 3, verificada a a associação de SNPS presentes nos genes da proteína ligante do fator de crescimento semelhante à insulina 3, coativador de proliferação de peroxissomo ativo por receptor gama 1A, subunidade 26S ATPse do proteassomo, do fator de aumento de desenvolvimento e de diferenciação 1, hormônio liberador de corticotrofina e proteína ligante de ácido graxo 4 com espessura de gordura em animais Canchim e MA. Além disso, a existência de regiões genômicas associadas com espessura de gordura subcutânea foi investigada em populações Canchim e MA usando um chip de 54 K em fenótipos extremos. Dentre as regiões com associação significativa, foram eleitas aquelas presentes no BTA14 para validar a associação por análise de haplótipos na população toda. SNPs nos genes do fator de aumento de desenvolvimento e de diferenciação 1 e da proteína ligante de ácido graxo 4 foram associados à variação de espessura de gordura subcutânea, enquanto que nenhuma associação foi observada para os SNPs dos genes proteína ligante ao fator de crescimento 7 semelhante à insulina 3, coativador de proliferação de peroxissomo ativo por receptor gama 1A, subunidade 26S ATPse do proteassomo e hormônio liberador de corticotrofina. Também foram associadas com a característica avaliada nesse trabalho, duas regiões cromossômicas do BTA14.

O emprego de \"Total Genome Scan\" em modelos genéticos de doenças complexas tem sido fundamental para seleção de regiões cromossômicas envolvidas com traços complexos. Em nosso laboratório, identificamos cinco regiões cromossômicas associadas ao traço quantitativo pressão arterial (BP-QTL) que explicam 43% da variação da pressão arterial numa progênie obtida a partir de animais espontaneamente hipertensos (SHR) e \"Brown Norway\" (BN). Os BP-QTLs foram, então, validados por desenvolvimento de linhagens congênicas, incluindo uma para o cromossomo 4 (SHR.BN4) cuja substituição das sequências SHR pelo do animal BN levou a redução da pressão arterial sistólica basal (~14 mm Hg). O objetivo deste trabalho foi identificar as variantes genéticas candidatas neste intervalo cromossômico com base em diferenças no padrão de expressão gênica e na presença de alterações genéticas não sinônimas \"missense\" ou em regiões regulatórias conservadas que possam estar envolvidas na gênese da hipertensão. Identificamos 533 genes com expressão renal, dentre os 682 do intervalo, sendo que 28 apresentaram padrão de expressão diferente entre amostras de animais adultos (congênico vs. SHR) e seis apresentaram alterações não sinônimas \"missense\". É importante salientar que dos genes diferentemente expressos, encontramos alterações estruturais em regiões conservadas com potencial de participar na regulação em 11. Em conjunto, utilizamos uma plataforma integrada para selecionar 34 genes candidatos no cromossomo 4, dos quais 17 genes serão priorizados, para ser investigados quanto sua contribuição na hipertensão arterial do SHR e na hipertensão primária humana / Total genome scan in genetic models of complex diseases have been instrumental to select candidate genes underlying complex traits. We previously mapped 5 blood pressure related quantitative trait loci (BP-QTLs) that explain about 43% of the BP variance in a progeny derived from Spontaneous Hypertensive Rat (SHR) and Brown Norway (BN) rats. The BP-QTLs were then validated by derivation of congenic strains, including one for chromosome 4 (SHR.BN4) in which a segment from BN replaced the SHR sequences reducing basal systolic BP (~14 mm Hg). The aim of this project is to identify the candidate genetic variants within the chromosome interval based on differences in renal gene expression patterns and structural changes in both non-synonymous missense or within adjacent regulatory sequences that may contribute to hypertension. We identified 533 genes with renal expression, out of 682 in the interval, in which 28 presented differences in expression pattern in adult samples (congenic vs. SHR) and six presented non-synonymous missense alterations. In addition, 11 out of 28 differentially expressed genes showed structural alterations in adjacent conserved regions that potentially contribute to gene regulation. Taken together, using the proposed combination of strategies, we selected 34 hypertensive candidate genes in chromosome 4, in which 17 will be prioritized, to be further explored to assess their contribution to hypertension in the SHR and to essential hypertension in humans

Au cours des quarante dernières années, l’optimisation des méthodes sylvicoles et l’introduction de variétés améliorées ont permis d’accroître considérablement la productivité du pin maritime. Pour permettre à la filière bois de disposer d’une matière première de qualité sur ce matériel amélioré, un programme de recherches multidisciplinaire a été développé afin d’étudier le déterminisme génétique de la qualité du bois. Neuf facteurs de transcription potentiellement impliqués dans la xylogenèse et l’adaptation des arbres à leur milieu, ont tout d’abord été séquencés dans la population Aquitaine, et leurs patrons de diversité nucléotidique ont été étudiés. Ces patrons ont été comparés à l’attendu de modèles neutres d’évolution et s’en écartent par un niveau élevé de déséquilibre de liaison et l’excès de mutations en fréquences intermédiaires détectés pour trois de ces gènes (HDZ31, LIM2 et MYB1). Ces résultats suggèrent des changements de taille de population affectant l’ensemble du génome, et l’action de sélection balancée sur l’un d’entre eux (MYB1). Les géniteurs de la population d’amélioration Aquitaine ont ensuite été génotypés pour 384 marqueurs moléculaires et évalués pour la croissance et les propriétés chimiques du bois. Ces données moléculaires et phénotypiques ont permis de mettre en évidence des associations significatives entre la variation pour le diamètre du tronc ou la teneur en cellulose du bois et deux marqueurs situés respectivement dans un facteur de transcription HD-Zip (HDZ31) et dans un gène encodant une fascicline. La cohérence des résultats de génétique évolutive et de génétique d’association ouvre ainsi des perspectives encourageantes pour la compréhension de l’architecture génétique de la formation du bois chez cette espèce. Cependant, le faible nombre d’associations significatives pose de nombreux problèmes théoriques et méthodologiques qui sont discutés en vue d’améliorations pour de nouveaux designs expérimentaux. / During the last four decades, the optimization of silvicultural and tree breeding methods has contributed to improve growth and wood homogeneity of maritime pine. In order to provide the different actors of the forestry wood-chain with high quality raw material, the genetic determinism and chemical components of wood quality are being studied in the frame of a multidisciplinary research program. First, nine transcription factors putatively involved in wood formation have been sequenced in the Aquitaine population, and their nucleotide diversity pattern studied. Since these genes potentially play important roles in the adaptation of trees to their environment, their patterns have been compared to those expected under neutral evolution. Strong departures from neutrality were observed, with high levels of linkage disequilibrium and an excess of intermediate frequency variants for three of them (HDZ31, LIM2 and MYB1), which could be linked to population size changes that affected the whole genome, and to balancing selection effects at one of them (MYB1). Secondly, the genitors of the Aquitaine breeding population were genotyped for 384 markers and evaluated for growth and wood chemical properties. Significant associations were detected for two markers, one in a HD-Zip transcription factor (HDZ31) with growth, and the other in a gene coding for a fasciclin protein with cellulose content. The consistency of evolutionary and molecular genetics opens encouraging perspectives for understanding the genetic architecture of wood formation in this species. However, the low number of associations detected raises several theoretical and methodological issues which are discussed for the perspective of improving future experimental designs.

Les adaptations florales à des pollinisateurs comme les changements de forme de la corolle entraînent souvent un isolement reproducteur et donc la spéciation. Malgré leur importance écologique, les mécanismes génétiques à l'origine de cette diversité de caractères sont encore mal compris, surtout en dehors des espèces modèles. L’objectif de mon projet de maîtrise était donc d'identifier les gènes impliqués dans la variation de la forme de la corolle entre deux espèces du genre Rhytidophyllum (famille des Gesneriaceae), qui ont des modes de pollinisation différents. La première, R. rupincola, a des fleurs tubulaires et est strictement pollinisée par les colibris, tandis que la seconde, R. auriculatum, a des fleurs plus ouvertes et est pollinisée par les colibris et les chauves-souris. Dans cette étude, nous avons fait une revue de littérature et utilisé une approche de transcriptomique comparative pour identifier des gènes candidats qui pourraient expliquer la variation de la forme florale entre R. auriculatum et R. rupincola. Nous avons ensuite testé leur association avec la variation de la forme de la corolle en utilisant la cartographie de loci de traits quantitatifs (QTLs) pour une population hybride F2. Les résultats ont montré que 7 des 29 gènes candidats étaient associés à 8 QTLs différents. La répartition et la fonction supposée de ces gènes suggèrent que la forme de la corolle est un trait complexe. Ce type d'étude est rarement entrepris chez des espèces non-modèles, mais il est important afin d'intégrer la génétique du développement floral dans une perspective évolutive. / Floral adaptations to specific pollinators like corolla shape changes often result in reproductive isolation and thus speciation. But despite their ecological importance, the genetic mechanisms behind this diversity of traits are still poorly understood, especially outside model species. Hence, our goal is to identify genes involved in corolla shape variation between two species of the Rhytidophyllum genus (Gesneriaceae family) from the West Indies, which is characterized by shifts in pollination modes during its evolution. The first one, R. rupincola, has a tubular corolla and is strictly pollinated by hummingbirds. The second one, R. auriculatum, has more open flowers and is pollinated by both hummingbirds and bats. We know from previous work that the variation in morphological floral traits between these species is explained by a few quantitative trait loci (QTLs) of moderate to small effect (Alexandre et al., 2015), but we still do not know which genes underly these loci. In this study, we surveyed the literature and used a comparative transcriptomic approach to identify candidate genes that could explain floral variation between R. auriculatum and R. rupincola. We then tested their association with corolla shape variation using QTL mapping for a F2 hybrid population. Results showed that 7 out of 29 candidate genes were included within 8 different QTL. The number, repartition and putative function of these genes suggest that corolla shape is a complex trait. This sort of investigation is rarely undertaken in non-model species, but is important to integrate developmental genetics with an evolutionary perspective.

L’hybridation avec des ressources génétiques allochtones est largement pratiquée chez les plantes ornementales pour introduire de nouveaux caractères. Au cours du 19e siècle, âge d’or de la sélection des rosiers en France, des rosiers asiatiques ont été introduits en Europe. L’objectif ici est d’étudier l’évolution de la diversité génétique des rosiers cultivés en France au cours de cette période. La diversité a été étudiée à l’échelle du génome puis à l’échelle de gènes candidats codant pour des caractères potentiellement sélectionnés au cours du 19e siècle. Un échantillon de 1228 rosiers illustrant la diversité génétique des rosiers français cultivés à cette période a été génotypé avec 32 microsatellites. Une large diversité, structurée en seize groupes génétiques et une différenciation entre les rosiers anciens européens et les rosiers asiatiques ont été détectées. Un déplacement du fond génétique des hybrides cultivés d’un type européen vers un type asiatique a été observé au cours du 19e siècle. Les croisements fréquents et/ou la sélection pour des caractères présents chez les rosiers asiatiques ont pu induire cette évolution. Certains caractères phénotypiques, comme la remontée de floraison, deviennent prépondérants. Onze gènes candidats ont été séquencés et leur diversité a été analysée sur un sous-échantillon de 365 rosiers. Parallèlement au fond génétique, certains gènes présentent un rapprochement génétique vers des allèles asiatiques. Pour le gène KSN, une augmentation de la fréquence d’allèles portant le rétrotransposon copia, responsable de la remontée de floraison, est observée. / Innovation in ornamental plant breeding is commonly obtained by hybridization with newly introduced genetic resources. During the 19th century, golden age for rose breeding in France, Asian roses were introduced in Europe. Our objective here was to study and explain the evolution of rose genetic diversity in France during this period of time. The diversity was studied at the genome scale and at the candidate gene scale. A large sample of 1228 garden roses illustrating the French rose diversity from this period of time was genotyped with 32 microsatellites markers. A wide diversity, structured into sixteen genetic groups, was observed. A geneticdifferentiation was detected between ancient European and Asian accessions and a continuous temporal shift was observed in cultivated hybrids from a European to an Asian genetic background during the 19th century.Frequent crosses with Asian roses along the 19th century and/or selection for Asiatic traits may have induced this shift. Some phenotypic traits, like continuous flowering, became overriding traits. Eleven candidate genes, which were potentially selected during the 19th century, were sequenced and their diversity was analyzed on a subsample of 365 roses. Simultaneously to the genetic background, some genes are gettingcloser to Asian alleles. For the KSN gene, an increase in the frequency of alleles carrying the retrotransposon copia, responsible for continuous flowering, is observed.

Flax (Linum usitatissimum L.) is a self-pollinated crop widely cultivated for fiber and oil production. Flaxseed is renowned for its health attributes but the presence of compounds, such as the heavy metal cadmium (Cd), is undesirable. Genomic studies in flax have produced large amounts of data in the last 15 years, providing useful resources to improve the genetic of this crop using genomics-based technologies and strategies. The goal of this thesis is therefore to capitalize on these advances to address the Cd problem and to propose solutions to improve breeding efficiencies. To find genomic-based solutions to Cd content, to the currently low breeding efficiency and to abiotic stress resistance in flax, this study utilized four major strategies: (1) genomic cross prediction, (2) gene family identification, (3) genome-wide association study (GWAS) and (4) genomic selection (GS). Characterization of the ATP-binding cassette (ABC) transporter and heavy metal associated (HMA) gene families was performed using the flax genome sequence. A total of 198 ABC transporter and 12 HMA genes were identified in the flax genome, of which nine were orthologous to Cd-associated genes in Arabidopsis, rice and maize. A transcriptomic analysis of eight tissues provided some support towards the functional annotation of these genes and confirmed the expression of these ABC transporter and HMA genes in flax seeds and other tissues. A diversity panel of 168 flax accessions was grown in the field at multiple locations and years and the seed content of 24 heavy metals (HMs) was measured. The panel was also sequenced and a single nucleotide polymorphism (SNP) dataset of nearly 43,000 SNPs was defined. A GWAS was conducted using these genotypic and phenotypic data and a total of 355 non-redundant quantitative trait nucleotides (QTNs) were identified for ten of the 24 metal contents. Overall, a total of 24 major and 331 minor effect QTNs were detected, including 11 that were pleiotropic. After allelic tests, 108 non-redundant QTNs were retained for eight of the ten metals and ranging from one for copper (Cu) to 70 for strontium (Sr). A total of 20 candidate genes for HM accumulation were identified at 12 of the 24 major QTN loci, of which five belonged to the ABC transporter family. Many of the metal contents, including Cd, appeared to be controlled by many genes of small effects; hence, GS is better suited than marker-assisted selection for application in breeding. To test this, predictive ability using ten GS statistical models was evaluated using trait-specific QTN and the random genome-wide 43K SNP datasets. Significantly higher predictive abilities were observed from the GS models built with the dataset made of QTNs associated with metal contents (70-80%) compared to that of the 43K dataset (10-25%). This study showed the feasibility of using GS to improve the predictive ability of polygenic traits such as metal content in seeds. GS can be applied in early generation selection to accelerate the improvement of abiotic stress resistance and either select low-Cd lines or discard high-Cd lines. These findings validate the use of a QTL-based strategy as a highly effective method for improving the efficiency of predictive ability of GS for highly complex traits such as resistance or tolerance to HM accumulation. Identification of both large and minor effect QTNs and/or pleiotropic effects hold potential for flax breeding improvement. Candidate gene functional validation can be performed using methods such as genome editing or targeting induced local lesions in genomes (TILLING).