Projects
Name
[LONGER] Impact of a supernumerary chromosome 21 on the regulation of gene transcription : study of the disomic MEST gene (7q32)
University
France (ANEMF) - University of Auvergne, Clermont-Ferrand
Domain
Genetics
Departement
CHU Estaing
Head
Pr. Philippe Vago
Tutor
Dr Laetitia Gouas
Languages
French, English
Duration
8 weeks
Availability
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
Yes Yes Yes Yes Yes Yes Yes No No No No Yes
Type of Research Project
- Basic science
What is the background of the project?
Recent developments in microarray technology allowed to observe a secondary, generalized transcriptional misregulation in human and mouse cells carrying a supernumerary chromosome 21. However, the mechanisms leading to the up- or down regulation of a disomic gene when carrying a trisomic chromosome 21 are not understood. Rozovski et al described a 13-fold increase in the expression of the MEST gene, in 7q32, in the chorionic villi cells of trisomic 21 fetuses compared to euploid fetuses. MEST (mesoderm specific transcript), also called PEG1 (paternally expressed gene-1) is an imprinting gene of interest because of its expression in mesoderm-derivatives such as the heart and intestines. To date, no association of the over-expression of MEST and the structural abnormalities of these organs in Down syndrome has been reported.
Our preliminary works are confirming the over-expression of MEST in chorionic villi cells of trisomic 21 fetuses although its expression varies greatly in euploid fetuses. Several questions are arising : Are the other imprinted genes in the flanking region of MEST also over-expressed ? Is the over-expression isoform-specific ? Is the over-expression allele-specific ? Is there an increase of the transcription rate or a decrease of the RNA turn-over ? Are there alterations of the epigenetic marks (DNA methylation, histone modification) in the regulatory sequences of the gene ?
The future works will attempt to answer these questions. The techniques and method used will be cell cultures, acid nucleic extraction, quantitative Reverse-Transcription-Polymerase Chain reaction, bi-sulfite sequencing, Chromatine-Immunoprecipitation (ChIp).

The student will have to perform experiments, interpret the results and write a report.

The student will acquire experience on cell cultures, acid nucleic extraction, PCR, quantitative RT-PCR, bi-sulfite sequencing, ChIP.
What is the aim of the project?
What techniques and methods are used?
What is the role of the student?
What are the tasks expected to be accomplished by the student?
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
No special skills are needed but a bench experience would be appreciated.
For the use of students considering participating in the project, further information can be found from the following articles:
Altug-Teber O, Bonin M, Walter M et al, Specific transcriptional changes in human fetuses with autosomal trisomies, Cytogenet Genome Res. 2007;119(3-4):171-84.
Rozovski U, Jonish-Grossman A, Bar-Shira A et al, Genome-wide expression analysis of cultured trophoblast with trisomy 21 karyotype, Human Reproduction. 2007; 22(9):25-38-2545
McMinn J, Wei M, Sadovsky Y, Thaker HM, Tycko B. Imprinting of PEG1/MEST isoform 2 in human placenta. Placenta. 2006 ; 27(2-3):119-26.
Are there any legal limitations in the student’s involvement
No
Hours
6
Type of students accepted
This project accepts:
- Medical students
- Pre-Medical students from the American-British system
Articles
- a:0:{}