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Gazave E.,Institute of Evolutionary Biology UPF CSIC | Gazave E.,Cornell University | Darre F.,Institute of Evolutionary Biology UPF CSIC | Darre F.,CNRS Alpine Ecology Laboratory | And 18 more authors.
Genome Research | Year: 2011

Copy number variants (CNVs) are increasingly acknowledged as an important source of evolutionary novelties in the human lineage. However, our understanding of their significance is still hindered by the lack of primate CNV data. We performed intraspecific comparative genomic hybridizations to identify loci harboring copy number variants in each of the four great apes: bonobos, chimpanzees, gorillas, and orangutans. For the first time, we could analyze differences in CNV location and frequency in these four species, and compare them with human CNVs and primate segmental duplication (SD) maps. In addition, for bonobo and gorilla, patterns of CNV and nucleotide diversity were studied in the same individuals. We show that CNVs have been subject to different selective pressures in different lineages. Evidence for purifying selection is stronger in gorilla CNVs overlapping genes, while positive selection appears to have driven the fixation of structural variants in the orangutan lineage. In contrast, chimpanzees and bonobos present high levels of common structural polymorphism, which is indicative of relaxed purifying selection together with the higher mutation rates induced by the known burst of segmental duplication in the ancestor of the African apes. Indeed, the impact of the duplication burst is noticeable by the fact that bonobo and chimpanzee share more CNVs with gorilla than expected. Finally, we identified a number of interesting genomic regions that present high-frequency CNVs in all great apes, while containing only very rare or even pathogenic structural variants in humans. © by Cold Spring Harbor Laboratory Press.


Aarnink A.,Laboratoire dImmunogenetique Moleculaire | Estrade L.,Laboratoire dImmunogenetique Moleculaire | Apoil P.-A.,Laboratoire dImmunogenetique Moleculaire | Kita Y.F.,Tokai University | And 3 more authors.
Immunogenetics | Year: 2010

To describe the polymorphism of the DRA gene in Macaca fascicularis, we have studied 141 animals either at cDNA level (78 animals from Mauritius, the Philippines, and Vietnam) or genomic level (63 animals from the Philippines, Indonesia, and Vietnam). In total, we characterized 22 cDNA DRA alleles, 13 of which had not been described until now. In the Mauritius population, we confirmed the presence of three DRA alleles. In the Philippine and Vietnam populations, we observed 11 and 14 DRA alleles, respectively. Only two alleles were present in all three populations. All DRA alleles but one differ from the consensus sequence by one to three mutations, most being synonymous; so, only seven DR alpha proteins were deduced from the 22 cDNA alleles. One DRA cDNA allele, Mafa-DRA*02010101, differs from all other alleles by 11 to 14 mutations of which only four are non-synonymous. The two amino acid changes inside the peptide groove of Mafa-DRA*02010101 are highly conservative. The very low proportion of non-synonymous/synonymous mutations is compatible with a purifying selection which is comparable to all previous observations concerning the evolution of the DRA gene in mammals. Homologues of the allele Mafa-DRA*02010101 are also found in two other Asian macaques (Macaca mulatta and Macaca nemestrina). The forces able to maintain this highly divergent allele in three different macaque species remain hypothetical. © 2010 Springer-Verlag.


Besbes S.,University of Sousse | Hamadou W.-S.,University of Sousse | Boulland M.-L.,Rennes University Hospital Center | Lefranc M.-P.,laboratoire dimmunogenetique moleculaire | And 5 more authors.
Bulletin du Cancer | Year: 2016

Introduction The monitoring of minimal residual disease (MRD) approach in patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) allows an early detection of residual clones inducing relapses and therefore appropriate therapy strategy. The molecular markers may identify and quantify the residual blasts in B-ALL with normal cytology. In this study, we aimed to use combined IKZF1, IGH and IGK immunoglobulin genes for diagnosis and MRD monitoring in B-ALL sample using MLPA, multiplex PCR and real-time quantitative PCR. Material We showed that multiplex PCR and MLPA are necessary and complementary to detect IKZF1 deletions. Results We have identified at the diagnosis clonal IGH rearrangement (VH3–JH5) and IKZF1 deletion (Δ4–7), which we have used it for MRD evaluation after induction chemotherapy. Despite the absence of chromosome abnormality, the patient may be classified in high-risk group with a relapse rate of residual blasts > 10−4 and sensitivity up to 10−5. This molecular approach enabled the patient's stratification, which was overlooked by classical methods. Conclusion The combined IKZF1 and immunoglobulin genes will be used as appropriate molecular tools for diagnosis and MRD assessment of B-lineage leukemias and introduced as a routine tests in Tunisian clinical laboratories. They will be useful to stratify patients into risk groups leading to better treatment strategy. © 2016 Société Française du Cancer


PubMed | laboratoire dimmunogenetique moleculaire, CHU F. Hached, Rennes University Hospital Center and University of Sousse
Type: Journal Article | Journal: Bulletin du cancer | Year: 2016

The monitoring of minimal residual disease (MRD) approach in patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) allows an early detection of residual clones inducing relapses and therefore appropriate therapy strategy. The molecular markers may identify and quantify the residual blasts in B-ALL with normal cytology. In this study, we aimed to use combined IKZF1, IGH and IGK immunoglobulin genes for diagnosis and MRD monitoring in B-ALL sample using MLPA, multiplex PCR and real-time quantitative PCR.We showed that multiplex PCR and MLPA are necessary and complementary to detect IKZF1 deletions.We have identified at the diagnosis clonal IGH rearrangement (VH3-JH5) and IKZF1 deletion (4-7), which we have used it for MRD evaluation after induction chemotherapy. Despite the absence of chromosome abnormality, the patient may be classified in high-risk group with a relapse rate of residual blasts>10The combined IKZF1 and immunoglobulin genes will be used as appropriate molecular tools for diagnosis and MRD assessment of B-lineage leukemias and introduced as a routine tests in Tunisian clinical laboratories. They will be useful to stratify patients into risk groups leading to better treatment strategy.

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