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Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation

Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation
Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation
The t(4;8)(p16;p23) translocation, in either the balanced form or the unbalanced form, has been reported several times. Taking into consideration the fact that this translocation may be undetected in routine cytogenetics, we find that it may be the most frequent translocation after t(11q;22q), which is the most common reciprocal translocation in humans. Case subjects with der(4) have the Wolf-Hirschhorn syndrome, whereas case subjects with der(8) show a milder spectrum of dysmorphic features. Two pairs of the many olfactory receptor (OR)-gene clusters are located close to each other, on both 4p16 and 8p23. Previously, we demonstrated that an inversion polymorphism of the OR region at 8p23 plays a crucial role in the generation of chromosomal imbalances through unusual meiotic exchanges. These findings prompted us to investigate whether OR-related inversion polymorphisms at 4p16 and 8p23 might also be involved in the origin of the t(4;8)(p16;p23) translocation. In seven case subjects (five of whom both represented de novo cases and were of maternal origin), including individuals with unbalanced and balanced translocations, we demonstrated that the breakpoints fell within the 4p and 8p OR-gene clusters. FISH experiments with appropriate bacterial-artificial-chromosome probes detected heterozygous submicroscopic inversions of both 4p and 8p regions in all the five mothers of the de novo case subjects. Heterozygous inversions on 4p16 and 8p23 were detected in 12.5% and 26% of control subjects, respectively, whereas 2.5% of them were scored as doubly heterozygous. These novel data emphasize the importance of segmental duplications and large-scale genomic polymorphisms in the evolution and pathology of the human genome.
dna, translocation, chromosome, inversion, cytogenetics, genome, research support, fluorescence, mothers, pathology, human, time, female, genetic, in situ hybridization, male, pair 4, multiple, abnormalities, receptors, role, syndrome, heterozygote, multigene family, chromosomes, odorant, pair 8, non-U.S.gov't, sequence analysis, evolution, humans, genetics
0002-9297
276-285
Giglio, S.
eb99db91-7676-46e2-9cb4-687fc3f4cb40
Calvari, V.
521aba29-1d3e-4a6c-a37b-907a3bbd87d3
Gregato, G.
c3ccc32d-9fad-437b-82b5-6858ae590e0d
Gimelli, G.
b41d1353-0805-4e6c-9d0a-b9a5f4ea4b43
Camanini, S.
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Giorda, R.
f372e6b6-09d4-4f3e-9efe-588a66c8e3e1
Ragusa, A.
a502c9f2-a4cd-48e4-8f6d-a44d35e7be7c
Guerneri, S.
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Selicorni, A.
8b37a335-24da-4626-8fec-a9ec57cc665e
Stumm, M.
bef95bc0-031d-4f04-b996-b4f866e00d7a
Tonnies, H.
a14d6169-7896-4d86-a695-51e38399535e
Ventura, M.
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Zollino, M.
f4c3cb66-bf32-4052-b3ef-38e35730a2c3
Neri, G.
c0c1392c-842e-4c2b-8731-ea54338d07d4
Barber, J.
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Wieczorek, D.
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Rocchi, M.
e1fb33db-eb2d-418f-a380-e49d4aa82bc3
Zuffardi, O.
08d1a96f-cd6e-49f4-a800-edea84c59131
Giglio, S.
eb99db91-7676-46e2-9cb4-687fc3f4cb40
Calvari, V.
521aba29-1d3e-4a6c-a37b-907a3bbd87d3
Gregato, G.
c3ccc32d-9fad-437b-82b5-6858ae590e0d
Gimelli, G.
b41d1353-0805-4e6c-9d0a-b9a5f4ea4b43
Camanini, S.
e2f0f2e0-6169-45ed-b5c8-e0579c2dba95
Giorda, R.
f372e6b6-09d4-4f3e-9efe-588a66c8e3e1
Ragusa, A.
a502c9f2-a4cd-48e4-8f6d-a44d35e7be7c
Guerneri, S.
0fa92f97-9f9a-4812-95e0-5e3a24ffd100
Selicorni, A.
8b37a335-24da-4626-8fec-a9ec57cc665e
Stumm, M.
bef95bc0-031d-4f04-b996-b4f866e00d7a
Tonnies, H.
a14d6169-7896-4d86-a695-51e38399535e
Ventura, M.
7facc630-7adb-4680-8595-7968f9d27c82
Zollino, M.
f4c3cb66-bf32-4052-b3ef-38e35730a2c3
Neri, G.
c0c1392c-842e-4c2b-8731-ea54338d07d4
Barber, J.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Wieczorek, D.
5f0b7c72-a471-4c7c-b5f5-7e372b7c9885
Rocchi, M.
e1fb33db-eb2d-418f-a380-e49d4aa82bc3
Zuffardi, O.
08d1a96f-cd6e-49f4-a800-edea84c59131

Giglio, S., Calvari, V., Gregato, G., Gimelli, G., Camanini, S., Giorda, R., Ragusa, A., Guerneri, S., Selicorni, A., Stumm, M., Tonnies, H., Ventura, M., Zollino, M., Neri, G., Barber, J., Wieczorek, D., Rocchi, M. and Zuffardi, O. (2002) Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation. American Journal of Human Genetics, 71 (2), 276-285. (doi:10.1086/341610).

Record type: Article

Abstract

The t(4;8)(p16;p23) translocation, in either the balanced form or the unbalanced form, has been reported several times. Taking into consideration the fact that this translocation may be undetected in routine cytogenetics, we find that it may be the most frequent translocation after t(11q;22q), which is the most common reciprocal translocation in humans. Case subjects with der(4) have the Wolf-Hirschhorn syndrome, whereas case subjects with der(8) show a milder spectrum of dysmorphic features. Two pairs of the many olfactory receptor (OR)-gene clusters are located close to each other, on both 4p16 and 8p23. Previously, we demonstrated that an inversion polymorphism of the OR region at 8p23 plays a crucial role in the generation of chromosomal imbalances through unusual meiotic exchanges. These findings prompted us to investigate whether OR-related inversion polymorphisms at 4p16 and 8p23 might also be involved in the origin of the t(4;8)(p16;p23) translocation. In seven case subjects (five of whom both represented de novo cases and were of maternal origin), including individuals with unbalanced and balanced translocations, we demonstrated that the breakpoints fell within the 4p and 8p OR-gene clusters. FISH experiments with appropriate bacterial-artificial-chromosome probes detected heterozygous submicroscopic inversions of both 4p and 8p regions in all the five mothers of the de novo case subjects. Heterozygous inversions on 4p16 and 8p23 were detected in 12.5% and 26% of control subjects, respectively, whereas 2.5% of them were scored as doubly heterozygous. These novel data emphasize the importance of segmental duplications and large-scale genomic polymorphisms in the evolution and pathology of the human genome.

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More information

Published date: 2002
Keywords: dna, translocation, chromosome, inversion, cytogenetics, genome, research support, fluorescence, mothers, pathology, human, time, female, genetic, in situ hybridization, male, pair 4, multiple, abnormalities, receptors, role, syndrome, heterozygote, multigene family, chromosomes, odorant, pair 8, non-U.S.gov't, sequence analysis, evolution, humans, genetics

Identifiers

Local EPrints ID: 59749
URI: http://eprints.soton.ac.uk/id/eprint/59749
ISSN: 0002-9297
PURE UUID: f2341e43-b93a-42b3-a51d-4d4eb4e968b5

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Date deposited: 03 Sep 2008
Last modified: 15 Mar 2024 11:17

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Contributors

Author: S. Giglio
Author: V. Calvari
Author: G. Gregato
Author: G. Gimelli
Author: S. Camanini
Author: R. Giorda
Author: A. Ragusa
Author: S. Guerneri
Author: A. Selicorni
Author: M. Stumm
Author: H. Tonnies
Author: M. Ventura
Author: M. Zollino
Author: G. Neri
Author: J. Barber
Author: D. Wieczorek
Author: M. Rocchi
Author: O. Zuffardi

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