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Review
. 2009 Aug;10(8):810-6.
doi: 10.1038/embor.2009.170.

Missed threads. The impact of pre-mRNA splicing defects on clinical practice

Diana Baralle  1 , Anneke Lucassen, Emanuele Buratti
Affiliations
Review

Missed threads. The impact of pre-mRNA splicing defects on clinical practice

Diana Baralle et al. EMBO Rep. 2009 Aug.
No abstract available

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Comparison between a classical genetic disease and a splicing-related alteration. (A) Schematic representation of the effects of gene deletion in hydrops fetalis. Normally, haemoglobin is made up of two α-subunits and two β-subunits that are transcribed by one β-gene on chromosome 11 (two copies per individual) and two α-genes on chromosome 16 (four copies per individual). People of Asian ancestry often have two α-globin genes deleted on the same chromosome 16, which results in mild thalassaemia. However, an offspring that inherits no α-genes from two heterozygous parents will develop hydrops fetalis, an often fatal disease in utero. In these cases, early diagnosis can be easily performed. (B) Mutations in the pre-mRNA splicing process, however, can affect several crucial steps in the recognition of introns and/or exons and can be further modified by many factors outside the mutation location. These context effects make it hard to determine the final outcome, eventual disease severity, and thus genetic counselling. BPS, branch-point site; SRE, splicing regulatory element.
Figure 2
Figure 2
Putative splicing mutations can be analysed using various publicly available bioinformatic tools that provide predictions on potential disruption of basic splicing sequences (acceptor, donor and branch-point sites), regulatory elements, and other features such as RNA secondary structure and protein binding sites. Splicing mutations are then collected in various databases, and the data stored can be used to improve the predictive analysis of mutation-detecting software.
Figure 3
Figure 3
Advantages and drawbacks of the diagnostic splicing tools commonly used in the laboratory. mRNA, messenger RNA; RT-PCR, reverse-transcription PCR.
Figure 4
Figure 4
Recipe for optimizing the identification of splicing mutations.
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See this image and copyright information in PMC

References

    1. Aartsma-Rus A, van Ommen GJ (2007) Antisense-mediated exon skipping: a versatile tool with therapeutic and research applications. RNA 13: 1609–1624 - PMC - PubMed
    1. Baird SD, Turcotte M, Korneluk RG, Holcik M (2006) Searching for IRES. RNA 12: 1755–1785 - PMC - PubMed
    1. Baralle D, Baralle M (2005) Splicing in action: assessing disease causing sequence changes. J Med Genet 42: 737–748 - PMC - PubMed
    1. Baralle M, Baralle D, De Conti L, Mattocks C, Whittaker J, Knezevich A, Ffrench-Constant C, Baralle FE (2003) Identification of a mutation that perturbs NF1, a gene splicing using genomic DNA samples and a minigene assay. J Med Genet 40: 220–222 - PMC - PubMed
    1. Baralle M, Skoko N, Knezevich A, De Conti L, Motti D, Bhuvanagiri M, Baralle D, Buratti E, Baralle FE (2006) NF1 mRNA biogenesis: effect of the genomic milieu in splicing regulation of the NF1 exon 37 region. FEBS Lett 580: 4449–4456 - PubMed

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