Methods for routine diagnosis of genomic rearrangements: multiplex PCR-based methods and future perspectives.
Germline and somatic genomic rearrangement play a relevant role in the pathogenesis of genetic disorders, and their identification is a fundamental task in molecular diagnosis. However, screening for structural genomic abnormalities is often not included in routine mutational analyses and consequently the proportion of rearrangements playing a pathogenic role in several genetic disorders is likely to be underestimated. A wide range of molecular techniques for the detection of large genomic rearrangements has been developed: some methods have the power to screen the whole genome, others are designed to analyze one or few loci that are known to be involved in a specific disease; some may detect balanced rearrangements, while others only unbalanced rearrangements; some are suitable for detection of germline abnormalities, yet others also detect somatic abnormalities. This review provides a brief summary of principles, applications and limitations of the methods available for the screening of genomic rearrangements, focusing on multiplex PCR-based protocols that are currently employed in routine detection of extended germline genomic deletions or duplications. Future developments based on microarray platforms and high-throughput sequencing are also discussed.
De Lellis
Laura
L
Department of Oncology & Neurosciences, University G. D'Annunzio, Chieti, Italy. lauradelellis@unich.it
Curia
Maria Cristina
MC
Veschi
Serena
S
Aceto
Gitana Maria
GM
Morgano
Annalisa
A
Cama
Alessandro
A
D015321:Gene Rearrangement; D015894:Genome, Human; D005854:Germ Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods*