Pseudoexons provide a mechanism for allele-specific expression of APC in familial adenomatous polyposis

Allele-specific expression (ASE) of the Adenomatous Polyposis Coli (APC) gene occurs in up to one-third of families with adenomatous polyposis (FAP) that have screened mutation-negative by conventional techniques. To advance our understanding of the genomic basis of this phenomenon, 54 APC mutation-...

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Autores principales: Nieminen, Taina T., Pavicic, Walter Hernán, Porkka, Noora, Kankainen, Matti, Järvinen, Heikki J., Lepistö, Anna, Peltomäki, Päivi
Formato: Articulo
Lenguaje:Inglés
Publicado: 2016
Materias:
Ciencias Médicas
Allele-specific expression
APC
Familial adenomatous polyposis
Pseudoexon
RNA-seq
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/86342
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-86342
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Allele-specific expression
APC
Familial adenomatous polyposis
Pseudoexon
RNA-seq
spellingShingle Ciencias Médicas
Allele-specific expression
APC
Familial adenomatous polyposis
Pseudoexon
RNA-seq
Nieminen, Taina T.
Pavicic, Walter Hernán
Porkka, Noora
Kankainen, Matti
Järvinen, Heikki J.
Lepistö, Anna
Peltomäki, Päivi
Pseudoexons provide a mechanism for allele-specific expression of APC in familial adenomatous polyposis
topic_facet Ciencias Médicas
Allele-specific expression
APC
Familial adenomatous polyposis
Pseudoexon
RNA-seq
description Allele-specific expression (ASE) of the Adenomatous Polyposis Coli (APC) gene occurs in up to one-third of families with adenomatous polyposis (FAP) that have screened mutation-negative by conventional techniques. To advance our understanding of the genomic basis of this phenomenon, 54 APC mutation-negative families (21 with classical FAP and 33 with attenuated FAP, AFAP) were investigated. We focused on four families with validated ASE and scrutinized these families by sequencing of the blood transcriptomes (RNA-seq) and genomes (WGS). Three families, two with classical FAP and one with AFAP, revealed deep intronic mutations associated with pseudoexons. In all three families, intronic mutations (c.646-1806T > G in intron 6, c.1408+729A > G in intron 11, and c.1408+731C > T in intron 11) created new splice donor sites resulting in the insertion of intronic sequences (of 127 bp, 83 bp, and 83 bp, respectively) in the APC transcript. The respective intronic mutations were absent in the remaining polyposis families and the general population. Premature stop of translation as the predicted consequence as well as co-segregation with polyposis supported the pathogenicity of the pseudoexons. We conclude that next generation sequencing on RNA and genomic DNA is an effective strategy to reveal and validate pseudoexons that are regularly missed by traditional screening methods and is worth considering in apparent mutation-negative polyposis families.
format Articulo
Articulo
author Nieminen, Taina T.
Pavicic, Walter Hernán
Porkka, Noora
Kankainen, Matti
Järvinen, Heikki J.
Lepistö, Anna
Peltomäki, Päivi
author_facet Nieminen, Taina T.
Pavicic, Walter Hernán
Porkka, Noora
Kankainen, Matti
Järvinen, Heikki J.
Lepistö, Anna
Peltomäki, Päivi
author_sort Nieminen, Taina T.
title Pseudoexons provide a mechanism for allele-specific expression of APC in familial adenomatous polyposis
title_short Pseudoexons provide a mechanism for allele-specific expression of APC in familial adenomatous polyposis
title_full Pseudoexons provide a mechanism for allele-specific expression of APC in familial adenomatous polyposis
title_fullStr Pseudoexons provide a mechanism for allele-specific expression of APC in familial adenomatous polyposis
title_full_unstemmed Pseudoexons provide a mechanism for allele-specific expression of APC in familial adenomatous polyposis
title_sort pseudoexons provide a mechanism for allele-specific expression of apc in familial adenomatous polyposis
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/86342
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