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Mapeamento genético e identificação de marcadores aflp, microssatélites genômicos e funcionais associados a parâmetros agroindustriais em cana-de-açúcarMancini, Melina Cristina [UNESP] 05 March 2010 (has links) (PDF)
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mancini_mc_me_jabo.pdf: 661667 bytes, checksum: 93a47f0775d75ffee87421531e42770c (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste trabalho foi construir um mapa de ligação e identificar marcadores associados aos componentes de produção (diâmetro, peso, altura, número de perfilhos e TCH) e parâmetros de qualidade (Fibra, Brix e Pol%Cana), em uma progênie derivada cruzamento entre o clone IACSP95-3018 e a cultivar IACSP93-3046, desenvolvidas pelo Programa de Melhoramento Cana IAC. Para tanto, foram utilizados marcadores moleculares do tipo AFLP e microssatélites genômicos e derivados de ESTs. A progênie mostrou grande variabilidade genética tanto para os componentes de produção quanto aos parâmetros de qualidade. O mapa de ligação foi composto por 231 marcadores segregando em dose única, distribuídos em 72 grupos de ligação (GL) que deram origem a dez grupos de homologia, com cobertura de 2436 centiMorgans (cM) e distância média entre marcadores de 10,55 cM, com distribuição irregular ao longo do cromossomo. O comprimento dos GLs variou de 1 a 96 cM. Os marcadores em dose única foram utilizados na análise de marcas simples para a identificação de prováveis QTLs associados às características fenotípicas obtidas em cana planta e cana soca. Um total de 155 associações marcador/característica foi encontrado a p<0,05 para as oito características avaliadas e 84 foram mapeadas em 34 GLs, sendo que apenas 16 foram observadas nos dois anos da cultura para a mesma característica / The objective of this study was to construct a linkage map and identify markers associated with yield components (diameter, weight, height, stalk number and productivity) and quality parameters (Brix, Fiber and Pol%Cana), in a progeny derived from a cross of the elite clone IACSP95-3018 and the variety IACSP93-3046, both developed from the IAC Sugarcane Breeding Program. We used molecular markers AFLP and genomic and derived from ESTs microsatellites. The progeny showed high genetic variability for both yield components and quality parameters. The genetic map was composed by 231 single markers dose, distributed onto 72 linkage groups (LG) which resulted in ten homology groups, with coverage 2436 centiMorgans (cM) and average distance between markers of 10.55, with irregular distribution along the chromosome. The length of the LG raging from 1 to 96 cM. Single marker trait association analysis was performed with the single dose markers to identify putative QTLs associated with the phenotypic measures obtained at cane plant and ratoon cane. A total of 155 marker/trait association was detected at p<0.05 for the eight traits evaluated and 84 were mapped in 34LGs, and only 16 were observed in both cycles for the same trait
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Mapeamento genético e identificação de marcadores aflp, microssatélites genômicos e funcionais associados a parâmetros agroindustriais em cana-de-açúcar /Mancini, Melina Cristina. January 2010 (has links)
Resumo: O objetivo deste trabalho foi construir um mapa de ligação e identificar marcadores associados aos componentes de produção (diâmetro, peso, altura, número de perfilhos e TCH) e parâmetros de qualidade (Fibra, Brix e Pol%Cana), em uma progênie derivada cruzamento entre o clone IACSP95-3018 e a cultivar IACSP93-3046, desenvolvidas pelo Programa de Melhoramento Cana IAC. Para tanto, foram utilizados marcadores moleculares do tipo AFLP e microssatélites genômicos e derivados de ESTs. A progênie mostrou grande variabilidade genética tanto para os componentes de produção quanto aos parâmetros de qualidade. O mapa de ligação foi composto por 231 marcadores segregando em dose única, distribuídos em 72 grupos de ligação (GL) que deram origem a dez grupos de homologia, com cobertura de 2436 centiMorgans (cM) e distância média entre marcadores de 10,55 cM, com distribuição irregular ao longo do cromossomo. O comprimento dos GLs variou de 1 a 96 cM. Os marcadores em dose única foram utilizados na análise de marcas simples para a identificação de prováveis QTLs associados às características fenotípicas obtidas em cana planta e cana soca. Um total de 155 associações marcador/característica foi encontrado a p<0,05 para as oito características avaliadas e 84 foram mapeadas em 34 GLs, sendo que apenas 16 foram observadas nos dois anos da cultura para a mesma característica / Abstract: The objective of this study was to construct a linkage map and identify markers associated with yield components (diameter, weight, height, stalk number and productivity) and quality parameters (Brix, Fiber and Pol%Cana), in a progeny derived from a cross of the elite clone IACSP95-3018 and the variety IACSP93-3046, both developed from the IAC Sugarcane Breeding Program. We used molecular markers AFLP and genomic and derived from ESTs microsatellites. The progeny showed high genetic variability for both yield components and quality parameters. The genetic map was composed by 231 single markers dose, distributed onto 72 linkage groups (LG) which resulted in ten homology groups, with coverage 2436 centiMorgans (cM) and average distance between markers of 10.55, with irregular distribution along the chromosome. The length of the LG raging from 1 to 96 cM. Single marker trait association analysis was performed with the single dose markers to identify putative QTLs associated with the phenotypic measures obtained at cane plant and ratoon cane. A total of 155 marker/trait association was detected at p<0.05 for the eight traits evaluated and 84 were mapped in 34LGs, and only 16 were observed in both cycles for the same trait / Orientador: Dilermando Perecin / Coorientadora: Luciana Rossini Pinto / Banca: Anete Pereira de Souza / Banca: Andréia da Silva Meyer / Mestre
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Mapeamento Genético do locus 1q 24.2 1q31.3 em famílias segregando periodontite agressiva / Genetic mapping of locus 1q 24.2 1q 31.3 in families segregating aggressive periodontitisFlavia Martinez de Carvalho 09 October 2009 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Um estudo sugere que o fenótipo da periodontite agressiva localizada está ligado a região 1q25. O objetivo do presente estudo foi aperfeiçoar o mapeamento genético da periodontite agressiva na região cromossômica supracitada em famílias clinicamente bem caracterizadas segregando a doença. A hipótese deste estudo é que variações genéticas localizadas no cromossomo 1 entre as regiões 1q 24.2 e 1q 31.3 contribuem para o fenótipo da periodontite agressiva. Como objetivos específicos, determinamos o modo de herança da periodontite agressiva através de análise de segregação, e verificamos a existência de ligação e/ou associação entre a região 1q 24.2-1q 31.3 e a periodontite agressiva. A análise de segregação foi executada no programa SEGREG do pacote SAGE versão 5.4.2 com base nos dados dos pedigrees das primeiras 74 famílias recrutadas neste estudo, totalizando 475 indivíduos (média de 6.4 indivíduos por família) de origem geográfica similar. Assumiu-se a herança Mendeliana como um locus autossômico com 2 alelos A e B, onde o alelo A estava associado ao fenótipo relevante. Cinco modos de transmissão (não homogêneo, Mendeliano homogêneo, homogêneo geral, semigeral, heterogêneo geral) foram testados assumindo que a prevalência da periodontite agressiva é de 1% sob o Equilíbrio de Hardy-Weinberg. Foram coletadas amostras de saliva de 54 das 74 famílias recrutadas, totalizando 371 amostras de saliva para a extração do DNA genômico. 21 polimorfismos de um único nucleotídeo (SNPs) foram selecionados dentro da região proposta e analisados por reação em cadeia da polimerase (PCR). Os genótipos foram obtidos pelo método TaqMan. A análise não paramétrica de ligação familial foi executada com o Programa Merlin. As detecções de transmissão (associação) foram executadas com os programas FBAT e PLINK. O modo de herança mais adequado para cada teste de susceptibilidade dos alelos executado foi o modelo semigeral (p=0,31). Este modelo de transmissão sugere que os alelos de risco para a periodontite agressiva são transmitidos pelos pais heterozigotos, fornecendo suporte para a hipótese que variantes genéticas exercem um papel importante na patogênese da periodontite agressiva e que poucos loci com efeitos relativamente pequenos contribuem para a doença, independente da interação com fatores ambientais. Os resultados mostram uma associação estatisticamente significante entre os SNPs rs1935881 (G>A) e rs1342913 (A>G) localizados no gene FAM5C e a periodontite agressiva (p=0,03). O sequenciamento das regiões codificantes de FAM5C não apresentaram mutação, mas foram encontradas duas mutações em íntrons do gene FAM5C próximas aos SNPs rs57694932 (A>G) e rs10494634 (A>T). Estas variantes não estão associadas a periodontite agressiva nesta população. Por outro lado, o haplótipo rs1935881-rs1342913 está associado a periodontite agressiva (p=0,009). Os resultados deste estudo suportam a hipótese de que o gene FAM5C contido na região 1q 24.2 a 1q 31.3 contribui para a etiopatogenia da periodontite agressiva e, portanto, pode ser sugerido como gene candidato. / It has been suggested that the localized aggressive periodontitis phenotype is linked to the region 1q25. The aim of this study was to fine map the chromosome interval suggested as containing a localized aggressive periodontitis locus in clinically well characterized group of families segregating aggressive periodontitis. The hypothesis of this study is that genetic variation located between 1q24.2 to 1q31.3 contributes to the phenotype of aggressive periodontitis. As specific aims, we evaluated the inheritance mode of aggressive periodontitis performing segregation analysis and, we tested the presence of linkage and or association between the target region of chromosome 1 and aggressive periodontitis. Segregation analysis was performed in pedigree data from the first 74 families, comprised of 475 individuals (average of 6.4 individuals per family) with similar geographic origin by the use of the SEGREG program of SAGE v.5.4.2. Mendelian inheritance was assumed to be through an autosomal locus with two alleles A and B, where the A allele was associated with the relevant phenotype. Five inheritance modes (homogeneous no transmission, homogeneous Mendelian transmission, homogeneous general transmission, semi-general transmission, heterogeneous general transmission) were tested assuming the prevalence of aggressive periodontitis as 1% and no deviations from Hardy-Weinberg equilibrium. Saliva samples were collected from 54 families, 371 individuals and DNA was extracted from this biological material. Twenty-one single nucleotide polymorphisms (SNPs) were selected and analyzed by standard polymerase chain reaction. The genotypes were obtained by the TaqMan method. The non-parametric analysis of familial linkage was performed with Merlin software. Analyses of transmission detection (association) were performed by FBAT and PLINK programs. The most parsimonious mode of inheritance in each susceptibility type tested was the semi-general transmission mode (p=0,31). This mode suggests an excess of risk alleles being transmitted from heterozygous parents. This result provides strong support for the hypothesis that genetic factors play a role in aggressive periodontitis and that a few loci, each with relatively small effects, contribute to aggressive periodontitis, with or without interaction with environmental factors. We found a statistically significant association between the SNPs rs1935881 (G>A) and rs1342913 (A>G) in the FAM5C gene and aggressive periodontitis (p=0.03). Sequence analysis of FAM5C coding regions did not disclose any mutations, but two variants in intronic regions of FAM5C gene: rs57694932 (A>G) and rs10494634 (A>T) were found. The two variants are not associated with aggressive periodontitis in this population. A stronger association could has seen between aggressive periodontitis and the haplotypes rs1935881-rs1342913 (p=0.009). This study supports the hypothesis that FAM5C gene might contribute to aggressive periodontitis and then, could be suggested as a candidate gene.
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Mapeamento Genético do locus 1q 24.2 1q31.3 em famílias segregando periodontite agressiva / Genetic mapping of locus 1q 24.2 1q 31.3 in families segregating aggressive periodontitisFlavia Martinez de Carvalho 09 October 2009 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Um estudo sugere que o fenótipo da periodontite agressiva localizada está ligado a região 1q25. O objetivo do presente estudo foi aperfeiçoar o mapeamento genético da periodontite agressiva na região cromossômica supracitada em famílias clinicamente bem caracterizadas segregando a doença. A hipótese deste estudo é que variações genéticas localizadas no cromossomo 1 entre as regiões 1q 24.2 e 1q 31.3 contribuem para o fenótipo da periodontite agressiva. Como objetivos específicos, determinamos o modo de herança da periodontite agressiva através de análise de segregação, e verificamos a existência de ligação e/ou associação entre a região 1q 24.2-1q 31.3 e a periodontite agressiva. A análise de segregação foi executada no programa SEGREG do pacote SAGE versão 5.4.2 com base nos dados dos pedigrees das primeiras 74 famílias recrutadas neste estudo, totalizando 475 indivíduos (média de 6.4 indivíduos por família) de origem geográfica similar. Assumiu-se a herança Mendeliana como um locus autossômico com 2 alelos A e B, onde o alelo A estava associado ao fenótipo relevante. Cinco modos de transmissão (não homogêneo, Mendeliano homogêneo, homogêneo geral, semigeral, heterogêneo geral) foram testados assumindo que a prevalência da periodontite agressiva é de 1% sob o Equilíbrio de Hardy-Weinberg. Foram coletadas amostras de saliva de 54 das 74 famílias recrutadas, totalizando 371 amostras de saliva para a extração do DNA genômico. 21 polimorfismos de um único nucleotídeo (SNPs) foram selecionados dentro da região proposta e analisados por reação em cadeia da polimerase (PCR). Os genótipos foram obtidos pelo método TaqMan. A análise não paramétrica de ligação familial foi executada com o Programa Merlin. As detecções de transmissão (associação) foram executadas com os programas FBAT e PLINK. O modo de herança mais adequado para cada teste de susceptibilidade dos alelos executado foi o modelo semigeral (p=0,31). Este modelo de transmissão sugere que os alelos de risco para a periodontite agressiva são transmitidos pelos pais heterozigotos, fornecendo suporte para a hipótese que variantes genéticas exercem um papel importante na patogênese da periodontite agressiva e que poucos loci com efeitos relativamente pequenos contribuem para a doença, independente da interação com fatores ambientais. Os resultados mostram uma associação estatisticamente significante entre os SNPs rs1935881 (G>A) e rs1342913 (A>G) localizados no gene FAM5C e a periodontite agressiva (p=0,03). O sequenciamento das regiões codificantes de FAM5C não apresentaram mutação, mas foram encontradas duas mutações em íntrons do gene FAM5C próximas aos SNPs rs57694932 (A>G) e rs10494634 (A>T). Estas variantes não estão associadas a periodontite agressiva nesta população. Por outro lado, o haplótipo rs1935881-rs1342913 está associado a periodontite agressiva (p=0,009). Os resultados deste estudo suportam a hipótese de que o gene FAM5C contido na região 1q 24.2 a 1q 31.3 contribui para a etiopatogenia da periodontite agressiva e, portanto, pode ser sugerido como gene candidato. / It has been suggested that the localized aggressive periodontitis phenotype is linked to the region 1q25. The aim of this study was to fine map the chromosome interval suggested as containing a localized aggressive periodontitis locus in clinically well characterized group of families segregating aggressive periodontitis. The hypothesis of this study is that genetic variation located between 1q24.2 to 1q31.3 contributes to the phenotype of aggressive periodontitis. As specific aims, we evaluated the inheritance mode of aggressive periodontitis performing segregation analysis and, we tested the presence of linkage and or association between the target region of chromosome 1 and aggressive periodontitis. Segregation analysis was performed in pedigree data from the first 74 families, comprised of 475 individuals (average of 6.4 individuals per family) with similar geographic origin by the use of the SEGREG program of SAGE v.5.4.2. Mendelian inheritance was assumed to be through an autosomal locus with two alleles A and B, where the A allele was associated with the relevant phenotype. Five inheritance modes (homogeneous no transmission, homogeneous Mendelian transmission, homogeneous general transmission, semi-general transmission, heterogeneous general transmission) were tested assuming the prevalence of aggressive periodontitis as 1% and no deviations from Hardy-Weinberg equilibrium. Saliva samples were collected from 54 families, 371 individuals and DNA was extracted from this biological material. Twenty-one single nucleotide polymorphisms (SNPs) were selected and analyzed by standard polymerase chain reaction. The genotypes were obtained by the TaqMan method. The non-parametric analysis of familial linkage was performed with Merlin software. Analyses of transmission detection (association) were performed by FBAT and PLINK programs. The most parsimonious mode of inheritance in each susceptibility type tested was the semi-general transmission mode (p=0,31). This mode suggests an excess of risk alleles being transmitted from heterozygous parents. This result provides strong support for the hypothesis that genetic factors play a role in aggressive periodontitis and that a few loci, each with relatively small effects, contribute to aggressive periodontitis, with or without interaction with environmental factors. We found a statistically significant association between the SNPs rs1935881 (G>A) and rs1342913 (A>G) in the FAM5C gene and aggressive periodontitis (p=0.03). Sequence analysis of FAM5C coding regions did not disclose any mutations, but two variants in intronic regions of FAM5C gene: rs57694932 (A>G) and rs10494634 (A>T) were found. The two variants are not associated with aggressive periodontitis in this population. A stronger association could has seen between aggressive periodontitis and the haplotypes rs1935881-rs1342913 (p=0.009). This study supports the hypothesis that FAM5C gene might contribute to aggressive periodontitis and then, could be suggested as a candidate gene.
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Genetic Analysis of Marsh Spot Resistance in Cranberry Common Bean (Phaseolus vulgaris L.)Jia, Bosen 22 August 2022 (has links)
Cranberry common bean (Phaseolus vulgaris L.) is planted worldwide and consumed as a critical food source of human protein, fibre, carbohydrates, and minerals. Marsh spot (MS) is a physiogenic disorder which severely impacts seed quality in common beans. Previous studies indicate that MS involves a nutritional disorder caused by Mn deficiency. However, the inheritance and genetic mechanism of MS resistance are still not fully understood.
To investigate the genetics of MS resistance, a population of 138 recombinant inbred lines (RILs) was developed from a bi-parental cross between a susceptible cultivar Messina and a resistant cultivar Cran09. The population and its two parents were evaluated for MS resistance during five consecutive years from 2015 to 2019 in both sandy and heavy clay soils in Morden, Manitoba, Canada. The severities of MS were rated and subsequently converted to MS resistance index (MSRI) and MS incidence (MSI). Statistical analyses indicated that MSI and MSRI were highly correlated (r = 0.96-0.99) and had high broad-sense heritability (H²) of 86.5% and 83.2%, respectively. Joint segregation analysis (JSA) of 18 phenotypic datasets from five years and two soil types showed that MS resistance was controlled by four major genes with genetic interactions - one of which may suppress the additive effect of the other three genes.
To identify the quantitative trait loci (QTL) and the candidate genes associated with the MS resistance, the 138 RILs and the two parents were sequenced using genotyping by sequencing approach. A total of 52,676 SNPs were detected. After further filtering with a threshold of minor allele frequency > 0.01 and call rate > 20%, 2,061 SNPs were retained and then imputed for genetic map construction and QTL mapping. A genetic map consisting of 2,058 SNP markers on 11 linkage groups or chromosomes was constructed, which covered 1,004 recombination blocks with a total length of 6,449 cM and an average block of 6.42 cM. Three linkage map-based QTL-mapping models ICIM-ADD, ICIM-EPI, and GCIM and one genome-wide association study (GWAS) model RTM-GWAS for 18 phenotypic datasets from different years and soil types were used for identification of QTL. A total of 36 QTL, including 21 of additive and 15 of epistatic effects, were identified. Functional gene annotation analysis revealed 151 Mn-related candidate genes across the common bean reference genome and 17 of them harbored the six QTL discovered in this study.
In conclusion, MS resistance in common bean is a highly heritable trait and controlled by several major and minor genes. The results of JSA and QTL mapping advance the current understanding of the genetic mechanisms of MS resistance in cranberry common bean, and provide additional resources for application in genomics-assisted breeding and potential isolation and functional characterization of the candidate genes.
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Incorporation of Genetic Marker Information in Estimating Modelparameters for Complex Traits with Data From Large Complex PedigreesLuo, Yuqun 20 December 2002 (has links)
No description available.
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Genetic analysis of earliness traits in chickpea (<i>Cicer arietinum</i> L.)Kabeta, Yadeta Anbessa 31 July 2007
The latter part of the reproductive growth phase in chickpea (<i>Cicer arietinum</i> L.) often coincides with declining temperature and wet conditions in western Canada, in sharp contrast to many other growing environments. This exacerbates the indeterminate nature of the crop, leading to excessive canopy development, and subsequently resulting in delayed maturity. The objectives of this study were to: i) determine the genetic relationships of short internode, double podding and early flowering traits with earliness of crop maturity; ii) determine the genetic control of major earliness traits in chickpea; iii) assess the patterns of post-flowering dry matter accumulation and partitioning to reproductive parts as related to earliness. <p>The results showed that double podding significantly reduced the number of days taken to maturity, under the conditions where this trait was sufficiently expressed. The best double podding genotypes, i.e. those with 1535% of the podded nodes bearing double pods, were about one week earlier than their single podding counterparts and standard checks. A physiological study revealed that the double podding parental genotype 272-2 partitioned a relatively greater proportion (about 58%) of the total dry matter to pods compared to 4254% in the single podding genotypes. Double podding increased the total number of pods set, and thus the increased demand for assimilates may have precluded further production of stems and leaves, resulting in an earlier transition of reproductive growth to physiological maturity. Days to flowering was positively associated with days to maturity, and partial path analysis revealed that days to flowering contributed to days to maturity indirectly via days to first pod maturity. Days to flowering explained 32% of the variation in days to first pod maturity. However, the short internode trait had an undesirable effect, in that all the short internode segregants were too late to mature. <p>Genetic studies revealed that days to flowering was determined by two major genes plus polygenes in chickpea in the short-season temperate environment of western Canada. The two major genes control over 65% of the phenotypic variation. Also, the additive component of genetic variance was significant for days to first podding, days to first pod maturity, reproductive period, and days to maturity; which is desirable for development of superior inbred cultivars of chickpea. These key phenological traits are interrelated but could be manipulated separately in the breeding process. Additional gain in earliness of crop maturity may be achieved through combined selection for these traits.
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Genetic analysis of earliness traits in chickpea (<i>Cicer arietinum</i> L.)Kabeta, Yadeta Anbessa 31 July 2007 (has links)
The latter part of the reproductive growth phase in chickpea (<i>Cicer arietinum</i> L.) often coincides with declining temperature and wet conditions in western Canada, in sharp contrast to many other growing environments. This exacerbates the indeterminate nature of the crop, leading to excessive canopy development, and subsequently resulting in delayed maturity. The objectives of this study were to: i) determine the genetic relationships of short internode, double podding and early flowering traits with earliness of crop maturity; ii) determine the genetic control of major earliness traits in chickpea; iii) assess the patterns of post-flowering dry matter accumulation and partitioning to reproductive parts as related to earliness. <p>The results showed that double podding significantly reduced the number of days taken to maturity, under the conditions where this trait was sufficiently expressed. The best double podding genotypes, i.e. those with 1535% of the podded nodes bearing double pods, were about one week earlier than their single podding counterparts and standard checks. A physiological study revealed that the double podding parental genotype 272-2 partitioned a relatively greater proportion (about 58%) of the total dry matter to pods compared to 4254% in the single podding genotypes. Double podding increased the total number of pods set, and thus the increased demand for assimilates may have precluded further production of stems and leaves, resulting in an earlier transition of reproductive growth to physiological maturity. Days to flowering was positively associated with days to maturity, and partial path analysis revealed that days to flowering contributed to days to maturity indirectly via days to first pod maturity. Days to flowering explained 32% of the variation in days to first pod maturity. However, the short internode trait had an undesirable effect, in that all the short internode segregants were too late to mature. <p>Genetic studies revealed that days to flowering was determined by two major genes plus polygenes in chickpea in the short-season temperate environment of western Canada. The two major genes control over 65% of the phenotypic variation. Also, the additive component of genetic variance was significant for days to first podding, days to first pod maturity, reproductive period, and days to maturity; which is desirable for development of superior inbred cultivars of chickpea. These key phenological traits are interrelated but could be manipulated separately in the breeding process. Additional gain in earliness of crop maturity may be achieved through combined selection for these traits.
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Contrôle génétique de la réponse à l’infection par des virus oncogènes en population endémique / Pas de titre traduitPedergnana, Vincent 07 October 2013 (has links)
La recherche de facteurs génétiques de susceptibilité aux infections virale dans des populations générales exhaustives endémiques est une approche originale en épidémiologie génétique. Nos travaux de thèse nous ont permis d’établir, dans une population endémique pour deux virus oncogènes MCPyV et HHV-8 au Cameroun et dans une population endémique pour le VHC en Egypte, plusieurs arguments forts en faveur d’une susceptibilité génétique aux infections par les virus oncogènes humains définies par la séropositivité/ séronégativité vis-à-vis du virus impliqué. Concernant l’infection par le MCPyV, dont les modes de transmission sont peu connus, nous avons mis en évidence l’existence de fortes corrélations familiales mère-enfant et entre enfants pour la séropositivité au virus, en faveur d’une transmission virale par contacts proches. Ces résultats sont similaires à ceux observés pour l’HHV-8, dans la même population, virus pour lequel la transmission par voie salivaire est l’hypothèse la plus forte. Concernant l’infection par l’HHV-8, nous avons identifié un locus majeur de prédisposition à l’infection par une analyse de ségrégation mettant un gène majeur mendélien autosomique récessif prédisposant à l’infection, suivie d’une analyse de liaison paramétrique utilisant le modèle de l’analyse de ségrégation. Concernant l’infection par le VHC, nous avons identifié par une analyse de liaison génétique un locus majeur de prédisposition à l’infection. Nous avons ensuite identifié, par une analyse d’association en génome entier sur une grande cohorte de plus de 6500 individus, trois signaux associés avec l’infection par le VHC. Par ailleurs, nous avons également réalisé une étude fine des variants du locus du gène IL28B, associés à la clairance du VHC, cohérente avec les résultats publiés au cours de nos travaux. L’identification de facteurs génétiques impliqués dans la susceptibilité aux infections virales oncogènes et aux cancers associés permettra de mieux comprendre la physiopathologie de la réponse à ces infections et les mécanismes intervenant depuis l’exposition virale jusqu’au développement de cancers. / The identification of genetic variants predisposing to viral infection in highly endemic general populations is an original approach in genetic epidemiology. Our work suggests a genetic control of the susceptibility to human oncogenic viruses infection, in a population in Cameroon in which MCPyV and HHV-8 are highly endemic and in an Egyptian population in which HCV is endemic. MCPyV is thought to be the etiological agent of Merkel cell carcinoma, but little is known about its distribution and modes of transmission. We provided evidence for familial aggregation of MCPyV infection status suggesting that MCPyV infection is acquired through close contact, possibly involving saliva and/or the skin, especially between young siblings and between mothers and their children. Infection with HHV-8 has been shown to display strong familial aggregation, in countries in which HHV-8 infection is endemic. Our segregation analysis provided strong evidence for a recessive major gene conferring predisposition to HHV-8 infection. The following linkage analysis identified a single region on chromosome 3p22 significantly linked to HHV-8 infection. This study provides the first evidence that HHV-8 infection in children in endemic areas has a strong genetic basis. Concerning HCV infection, we performed a linkage analysis that mapped a major locus predisposing to HCV infection in an Egyptian cohort. We then performed a genome-wide association study in more than 6500 individuals, identifying three signals associated with HCV infection. Finally we investigated the role of several IL28B SNPs in HCV spontaneous clearance in an Egyptian population. The results confirm the major role of IL28B variants in the spontaneous clearance of HCV genotype 4 infection in an Egyptian population. The identification of genetic variants predisposing to viral infection should greatly improve our understanding of the molecular mechanisms involved in the response to these infections and may also unravel new pathways for investigation in viruses-associated diseases, such as cancer.
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