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Laurent Bracco

Publications and source records attributed to Laurent Bracco.

5 recordsLinked to original sources
PubMed2006

Methods and platforms for the quantification of splice variants' expression.

The relatively limited number of human protein encoding genes highlights the importance of the diversity generated at the level of the mRNA transcripts. As alternative RNA splicing plays a key role in mediating this diversity, it becomes critical to develop the tools and platforms that will deliver quantitative information on the specific expression levels associated with splice isoforms. This chapter describes the constraints generated by this global transcriptome analysis and the state-of-the-art techniques and products available to the scientific community.

Alternative Splicing↗
PubMed2006

Alternative isoform discrimination by the next generation of expression profiling microarrays.

Microarray expression profiling has revolutionised the way that many therapeutic targets have been identified over the past 10 years. High-density microarrays have allowed scientists to simultaneously scrutinise the expression of all genes encoded on a given genome. Although the data collected from classically designed microarrays greatly enriched the pool of information available to help guide the selection and design of new therapeutic strategies, they were unable to tell the complete story. The major limitation with most array designs is that they can only produce a global expression value for all transcripts produced from a specific locus and cannot monitor each individual alternative isoform produced from the interrogated locus. Recently, new array designs have been described, and become commercially available, that can efficiently monitor individual alternatively spliced isoforms produced from a single locus, allowing the research community to get a more accurate picture of the biological landscape of the expressed transcripts.

Alternative Splicing↗
PubMed2005

A microarray configuration to quantify expression levels and relative abundance of splice variants.

Over the past decade, alternative RNA splicing has raised a great interest appearing to be of high importance in the generation of expression diversity. This regulatory process plays a critical role in the normal development and its impact on the initiation and development of human disorders as well as on the pharmacological properties of drugs is increasingly being recognized. Only few studies describe specific alternative splicing expression profiling. Microarray strategies have been conceived to address alternative splicing events but with very few experimental data related to their abilities to provide true quantification values. We have developed a specific microarray configuration relying on a few, well optimized probes per splice event. Basically, five probes of 24mer are used to fully characterize a splice event. These probes are of two types, exon probes and junction probes, and are either specific to a splice event or not. The performances of such a 'splice array' were validated on synthetic model systems and on complex biological materials. The results indicate that DNA chips based on this design combining exon and junction derived probes enable the detection and, absolute and relative quantification of splice variants. In addition, this strategy is compatible with all the microarrays that use oligonucleotide probes.

Alternative Splicing↗
PubMed2003

The relevance of alternative RNA splicing to pharmacogenomics.

The importance of alternative RNA splicing in the generation of genetic diversity is now widely accepted. This article highlights how alternative RNA splicing can have an impact on drug efficacy and safety, and demonstrates its potential pharmacogenomic value. The analysis of the repertoire of alternative RNA splicing events could potentially identify markers of pharmacogenomic relevance with high sensitivity and specificity and also provides a route through which genes can be selected for single nucleotide polymorphism (SNP) genotyping. Recent methodological advances, including microarray and splice-dedicated expression profiling, have made it possible to perform high-throughput alternative splicing analyses.

Alternative Splicing↗