Aneuploidy: the impact of chromosome imbalance on nuclear organization and overall genome expression.
The organization and dynamics of chromatin within the interphase nucleus as chromosome territories (CTs) and the relationship with transcriptional regulation are not fully understood. We studied a natural example of chromosomal disorganization: aneuploidy due to trisomies 13, 18 and 21. We hypothesized that the presence of an extra copy of one chromosome alters the CT distribution, which perturbs transcriptional activity. We used 3D-FISH to study the position of the chromosomes of interest (18 and 21) in cultured amniocytes and chorionic villus cells from pregnancies with a normal or aneuploid karyotype. We studied the volumes of nuclei and CTs in both conditions and performed a compared transcriptome analysis. We did not observe any differences between euploid and aneuploid cells in terms of the radial and relative CT positions, suggesting that the same rules govern nuclear organization in cases of trisomy. We observed lower volumes for CTs 18 and 21. Overall genome expression profiles highlighted changes in the expression of a subset of genes in trisomic chromosomes, while the majority of transcriptional changes concerned genes located on euploid chromosomes. Our results suggest that a dosage imbalance of the genes on trisomic chromosomes is associated with a disturbance of overall genomic expression.
UFR des Sciences de la Santé Simone Veil, GIG, EA7404, Montigny le Bretonneux, France.|Génomique, Epigénétique et Physiopathologie de la Reproduction, U1016 INSERM-UMR 8104 CNRS, Institut Cochin, Université Paris Descartes, Paris, France.|Service de Cytogénétique, APHP - Hôpital Cochin, Paris, France.|Service de Cytogénétique, Centre Hospitalier Intercommunal de Poissy Saint-Germain-en-Laye, Poissy, France.
B
B
Hervé
Service de Cytogénétique, APHP - Hôpital Cochin, Paris, France.
A
A
Coussement
Plate-Forme Cochin Imagerie, Université Paris Descartes, Institut Cochin, Paris, France.
T
T
Gilbert
Genom'ic, Université Paris Descartes, Institut Cochin, Paris, France.
F
F
Dumont
Genom'ic, Université Paris Descartes, Institut Cochin, Paris, France.
S
S
Jacques
Génomique, Epigénétique et Physiopathologie de la Reproduction, U1016 INSERM-UMR 8104 CNRS, Institut Cochin, Université Paris Descartes, Paris, France.|Service de Biochimie et Génétique Moléculaire, APHP - Hôpital Cochin, Paris, France.
L
L
Cuisset
Genom'ic, Université Paris Descartes, Institut Cochin, Paris, France.
M
M
Chicard
Service de Cytogénétique, APHP - Hôpital Cochin, Paris, France.
S
S
Hizem
Plate-Forme Cochin Imagerie, Université Paris Descartes, Institut Cochin, Paris, France.
P
P
Bourdoncle
Genom'ic, Université Paris Descartes, Institut Cochin, Paris, France.
F
F
Letourneur
Unité fonctionnelle de Cytogénétique-Département de Génétique- APHP, Hôpital Robert Debré, Paris, France.
C
C
Dupont
UFR des Sciences de la Santé Simone Veil, GIG, EA7404, Montigny le Bretonneux, France.|Service de Cytogénétique, Centre Hospitalier Intercommunal de Poissy Saint-Germain-en-Laye, Poissy, France.
F
F
Vialard
Génomique, Epigénétique et Physiopathologie de la Reproduction, U1016 INSERM-UMR 8104 CNRS, Institut Cochin, Université Paris Descartes, Paris, France.|Service de Cytogénétique, APHP - Hôpital Cochin, Paris, France.
A
A
Choiset
Génomique, Epigénétique et Physiopathologie de la Reproduction, U1016 INSERM-UMR 8104 CNRS, Institut Cochin, Université Paris Descartes, Paris, France.|Service de Cytogénétique, APHP - Hôpital Cochin, Paris, France.
J-M
JM
Dupont
D000328:Adult; D000650:Amnion / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure*; D002824:Chorionic Villi / Q000378:metabolism / Q000473:pathology; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure; D025063:Chromosome Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics / Q000378:metabolism; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics / Q000378:metabolism; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D005865:Gestational Age; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D007621:Karyotyping; D011247:Pregnancy; D061251:Primary Cell Culture; D059467:Transcriptome; D014314:Trisomy / Q000235:genetics* / Q000473:pathology; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
D002843:Chromatin
3D-FISH; aneuploidy; chromosome territories; interphase nucleus; transcriptome analysis