Download laboratory of developmental genetics and genetic analysis

LABORATORY OF DEVELOPMENTAL GENETICS AND GENETIC
ANALYSIS
Laboratory head: Dr. Ecovoiu Al. Alexandru
[email protected]
Members:
[email protected]
[email protected]
[email protected]
[email protected]
Prof. Dr. Lucian Gavrila
Dr. Magdalena (Georgescu) Laura Monica
Doctorand Graur Marian
Doctorand Ratiu Attila Cristian
Developmental genetics and Genetic analysis laboratory, pertaining to the Institute of Genetics,
employs Drosophila melanogaster (the fruit fly, the vinegar fly) as an experimental model. We are
involved in functional analysis of some genes involved in development, in revealing biological
significance of transposons mobilization patterns, and also in an effort aiming to elucidate genetic
mechanisms responsible for human disorders like cancer, Silver-Russell, Ehlers-Danlos and Angelmann
syndromes.
Our studies are focused on gammaCop, CG6199, As, ARP-like and CG6664 genes which are
structural orthologs of human genes associated with the above mentioned syndromes. All of these genes
are located on the third Drosophila chromosome and we are currently using reverse genetics in order to
analyse them. The experimental strategy relays on obtaining polyallelic series for each gene, which would
allow us to investigate different mutant phenotypes that reveal gene functions.
Our contribution to the international effort aiming to generate specific polyallelic series is stored
in FlyBase (www.flybase.org), where there are detailed reports describing different mutant alleles. Up to
February 2008, 14 out of the 20 reported mutant alleles of gammaCop gene and one out of the three
known mutant alleles for ARP-like gene listed in FlyBase were obtained in our laboratory. In addition, we
generated a new lethal allele of CG6199 gene, for which there are reported only three other registered
mutant alleles. The new allele sequence was recently sent to GenBank/NCBI (accession number
EU240219) and FlyBase is going to integrate it in the specific report. About the other two genes we are
focused on there is also only a little knowledge, meaning that their functional analysis is in an incipient
state. Consequently, we are currently running mutagenesis projects in order to generate specific
polyallelic series through insertional/excisional mutagenesis.
In order to obtain mutant alleles, we performed mobilization with a Δ2-3 transposase source of
diferent P artificial transposons located in or within the close proximity of the above mentioned genes.
This method allowed us to obtaine both hypomorphic and lethal alleles. Genetic analysis of γCop11a,
γCop14a and γCop16b hypomorphic alleles demonstrated that gammaCop gene, which has a human
counterpart susceptible to be involved in Silver-Russell syndrome, exhibits developmental pleiotropy.
Our studies reveal that gammaCop is involved in both embryo development and in female/male fertility,
and manifests both parental and zygotic effects. Another example is illustrated by an ARP-like lethal
allele obtained in our laboratory, which in homozygous condition is responsible for the development of
tumor-like structures in larvae and pupae. Such a mutant phenotype is a very promising one, since human
structural ortholog gene, symbolized ARP, is associated with various types of cancer.
Further studies of the altered phenotypes determined by any of these mutant alleles will allow us
to conclude if they are true functional orthologs of their human counterpart’s genes. The confirmation of
such a functional relationship will open the gate to capitalize on Drosophila as a model in order to
decipher the genetic mechanisms of the medical disorders we have in study. Extrapolating such
experimental data to humans would be the first step in designing new therapeutic strategies for these so
far incurable diseases.
Other fields of interest of our laboratory are the investigation of ionizing radiation on Drosophila
genome and the use of FISH technique in fruit fly genome investigation.
RELEVANT PUBLICATIONS:
1. Gavrila L., Ecovoiu A. A., Georgescu L.M., 2001. Localizing genes in Drosophila melanogaster
polytene chromosomes by fluorescence in situ hybridization. J. Cell. Mol. Med., Vol. 5, No 1,
pag. 74-78.
2. Ecovoiu A. A., Mink M., Georgescu L.M., Graur M., Gavrilă L., 2002. Genetic data confirm
association of {PlacW}gammaCopS057302 insertion in Drosophila melanogaster gammaCop gene
with the mutant phenotype of l/3/S057302 transgenic line. Analele Universitatii Bucuresti, LI:
pag. 41-47.
3. Ecovoiu A. A., Mink, M., Graur, M., Georgescu, L.M., Gavrila, L., 2005. Generation of putative
lethal and hypomorphic gammaCop gene alleles by mobilization of P{lacW}gammaCopS057302
insertion during male germ line development of Drosophila melanogaster. Roum. Biotechnol.
Lett., Vol. 10, No. 1, pag. 1985-1994.
4. Georgescu, L.M., Ecovoiu A. A., Graur, M. si Gavrila L., 2005. P{EP}EP3171 allele of ARP-like
gene from Drosophila melanogaster is not lethal. Roum. Biotechnol. Lett., Vol. 10, No. 1, pag.
1995-2000.
5. Marian G., Raquel de Mello e Alegria, M. Ecovoiu A. A., Gavrilă L. 2005. Phenotype analysis of
putative transposon mutagenesis of Drosophila melanogaster CG6199 gene, a potential
experimental model for human collagen disorders. Roumanian Journal of Genetics, vol.1, No.1,
pag. 109-113.
6. Graur M., Ecovoiu A. A., Timus D., Georgescu L. M., Gavrila L. 2005. Effects of X and beta
irradiation on Drosophila male germ-line. Romanian Journal of Genetics, vol.1, No.2, pag.8187.
7. Georgescu L. M., Ecovoiu A. A., Graur M., Gavrila L., 2006. “Functional investigation of fruitfly ARP-like gene - an ortholog of human ARP gene”, Icrea-Irb-Conference On Drosophila,
Barcelona, Spania.
8. Georgescu L. M., Ecovoiu A. A., Gavrila L.. 2006. “A genetic analysis of ARP-like gene from
Drosophila melanogaster, a structural ortholog of human ARP gene, mutated in early stage
tumors”. Modern trends in biological sciences: seeking an integrative approach, Poster pp.52,
Szeged, Hungary.
9. Ecovoiu A. A., Savu L., Otelea D., Gavrila L., 2007. Analysis of a polyallelic series reveals
gammaCop pleiotropy during development of Drosophila melanogaster. EDRC 2007 (20th
European Drosophila Research Conference) Abstract Book, pag. 98.
10. Ecovoiu A. A., 2001. „Aplicaţii ale ingineriei genetice în investigarea proceselor de dezvoltare
la eucariote” si „Genetica ovogenezei la Drosophila”, in „Progrese in Biotehnologie”, sub
coordonarea: Dumitru I.F. si Toma N. Editura Ars Docendi, Bucuresti, ISBN 973-8118-69-7, p.
232-247 si p. 269-284.
11. Ecovoiu A. A., Georgescu L. M., 2003. “Drosophila melanogaster - Model experimental în
Genetică”. Editura Ars Docendi, ISBN 973-558-078-0, 131 p.
12. Ecovoiu A. A., 2003. in “GENOMICA - Un tratat despre genom, de la virusuri la om”. Ed.
Enciclopedică, Bucureşti. 2003, vol. II, sub red. Prof Dr. Lucian Gavrila, Ed. Enciclopedica,
Bucuresti, pag. 69-79 Cap. II: Producerea de proteine prin tehnologia ADN recombinant,
pag.217-268 Cap IX: Genomul sistemelor macromoleculare acelulare: virusuri, virusoizi,
viroizi şi prioni, pag. 821-859 Cap. XXXIV: Organizarea structural-funcţională a genomului la
Drosophila melanogaster.
13. Ecovoiu A. A., Mink M., Gavrila L., 2002. The embryonic-lethal gammaCop is essential in
Drosophila development. DDBJ/EMBL/GenBank, Accession number AJ492220.
14. Ecovoiu A. A., Otelea D., Savu L. and Gavrila L. 2005. Sequence of gammaCop11a
hypomorphic allele. DDBJ/EMBL/GenBank, Accesion number DQ279401.
15. Ecovoiu A. A., Otelea D., Savu L. and Gavrila L. 2005. Sequence of gammaCop14a
hypomorphic allele. DDBJ/EMBL/GenBank, Accesion number DQ279402.
16. Ecovoiu A. A., Otelea D., Savu L. and Gavrila L. 2005. Sequence of gammaCop16b
hypomorphic allele. DDBJ/EMBL/GenBank, Accesion number DQ279403.
17. Georgescu L. M., Ecovoiu A. A. and Gavrila L., 2006. ARP-like 35E allele is a recessive lethal
deficiency. DDBJ/EMBL/GenBank, Accesion number DQ649527.
18. Graur, M., Ecovoiu, A. A., Otelea, D., Savu, L., Ratiu, A.C. and Gavrila, L., 2007. CG6199 gene
is essential for Drosophila development. DDBJ/EMBL/GenBank, Accesion number EU240219.