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Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY

Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY
Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY
Mutation-induced activation of splice sites in intronic repetitive sequences has contributed significantly to the evolution of exon–intron structure and genetic disease. Such events have been associated with mutations within transposable elements, most frequently in mutation hot-spots of Alus. Here, we report a case of Alu exonization resulting from a 367-nt genomic COL4A5 deletion that did not encompass any recognizable transposed element, leading to the Alport syndrome. The deletion brought to proximity the 5? splice site of COL4A5 exon 33 and a cryptic 3? splice site in an antisense AluY copy in intron 32. The fusion exon was depleted of purines and purine-rich splicing enhancers, but had low levels of intramolecular secondary structure, was flanked by short introns and had strong 5? and Alu-derived 3? splice sites, apparently compensating poor composition and context of the new exon. This case demonstrates that Alu splice sites can be activated by outlying deletions, highlighting Alu versatility in shaping the exon–intron organization and expanding the spectrum of mutational mechanisms that introduce repetitive sequences in mRNAs.
Alu, collagen, exonization, intron, rna processing
2324-9269
451-453
Nozu, Kandai
5b83b5a2-174f-4fc4-81aa-58f7466ea38b
Iijima, Kazumoto
0025351f-84e0-429a-ba94-befdbe081d1a
Ohtsuka, Yasufumi
72115036-f4ec-4939-88c7-c31fc11d579b
Fu, Xue Jun
a1d4f6e2-a9ec-4e5d-b6f4-ea03801e6986
Kaito, Hiroshi
ca0486de-6b30-44c4-a7f0-5e103f701fa1
Nakanishi, Koichi
314cded2-4bdb-4275-95c9-0c8cd73c887e
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Nozu, Kandai
5b83b5a2-174f-4fc4-81aa-58f7466ea38b
Iijima, Kazumoto
0025351f-84e0-429a-ba94-befdbe081d1a
Ohtsuka, Yasufumi
72115036-f4ec-4939-88c7-c31fc11d579b
Fu, Xue Jun
a1d4f6e2-a9ec-4e5d-b6f4-ea03801e6986
Kaito, Hiroshi
ca0486de-6b30-44c4-a7f0-5e103f701fa1
Nakanishi, Koichi
314cded2-4bdb-4275-95c9-0c8cd73c887e
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e

Nozu, Kandai, Iijima, Kazumoto, Ohtsuka, Yasufumi, Fu, Xue Jun, Kaito, Hiroshi, Nakanishi, Koichi and Vorechovsky, Igor (2014) Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY. Molecular Genetics and Genomic Medicine, 2 (5), 451-453. (doi:10.1002/mgg3.89). (PMID:25333070)

Record type: Article

Abstract

Mutation-induced activation of splice sites in intronic repetitive sequences has contributed significantly to the evolution of exon–intron structure and genetic disease. Such events have been associated with mutations within transposable elements, most frequently in mutation hot-spots of Alus. Here, we report a case of Alu exonization resulting from a 367-nt genomic COL4A5 deletion that did not encompass any recognizable transposed element, leading to the Alport syndrome. The deletion brought to proximity the 5? splice site of COL4A5 exon 33 and a cryptic 3? splice site in an antisense AluY copy in intron 32. The fusion exon was depleted of purines and purine-rich splicing enhancers, but had low levels of intramolecular secondary structure, was flanked by short introns and had strong 5? and Alu-derived 3? splice sites, apparently compensating poor composition and context of the new exon. This case demonstrates that Alu splice sites can be activated by outlying deletions, highlighting Alu versatility in shaping the exon–intron organization and expanding the spectrum of mutational mechanisms that introduce repetitive sequences in mRNAs.

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Accepted/In Press date: 9 May 2014
e-pub ahead of print date: 28 May 2014
Published date: September 2014
Keywords: Alu, collagen, exonization, intron, rna processing
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 371786
URI: http://eprints.soton.ac.uk/id/eprint/371786
ISSN: 2324-9269
PURE UUID: d964c1a0-b144-4b6a-b16a-695a56eb8d8c
ORCID for Igor Vorechovsky: ORCID iD orcid.org/0000-0002-6740-6502

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Date deposited: 18 Nov 2014 10:41
Last modified: 15 Mar 2024 03:16

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Contributors

Author: Kandai Nozu
Author: Kazumoto Iijima
Author: Yasufumi Ohtsuka
Author: Xue Jun Fu
Author: Hiroshi Kaito
Author: Koichi Nakanishi

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