High-sensitive microarray substrates specifically designed to improve sensitivity for the identification of fetal paternally inherited sequences in maternal plasma.
BACKGROUND
The identification of very low-levels of minority sequences has interesting clinical and diagnostic applications. Among these, non-invasive prenatal diagnosis of genetic diseases on fetal DNA circulating in maternal plasma is an emerging field of application.


METHODS
A combined approach based on innovative microarray slides coated with a special copolymer was developed for the identification of three polymorphisms located in the causative gene for cystic fibrosis (CF). This technique was applied to the analysis of fetal DNA in maternal plasma from four couples that carried different allelic variants.


RESULTS
The use of highly sensitive slides correctly identified fetal paternally inherited alleles without any enrichment strategy.


CONCLUSIONS
Our results confirm that the high fluorescence signal provided by the optimized substrate may be applied to the identification of any fetal paternally inherited sequence. This helps extend the application of non-invasive prenatal diagnosis to genetic diseases caused by predominant mutations or minor rare molecular defects.
Bruno
Francesca
F
Genomic Unit for the Diagnosis of Human Pathologies, Center for Genomics, Bioinformatics and Biostatistics, San Raffaele Scientific Institute, Milan, Italy.
Damin
Francesco
F
Causarano
Vincenza
V
Galbiati
Silvia
S
Di Carlo
Gabriele
G
Seia
Manuela
M
Porcaro
Luigi
L
Ferrari
Maurizio
M
Chiari
Marcella
M
Cremonesi
Laura
L
D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics; D004247:DNA / Q000097:blood*; D005260:Female; D005333:Fetus; D005456:Fluorescent Dyes / Q000737:chemistry; D030342:Genetic Diseases, Inborn / Q000175:diagnosis*; D005838:Genotype; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D013379:Substrate Specificity
D005456:Fluorescent Dyes; D004247:DNA