Stefano Gambardella^1,7, Erika Ciabattoni³, Francesca Motta³, Giusy Stoico³, Francesca Gullotta², MichelaBiancolella^1,6, Anna Maria Nardone², Antonio Novelli⁴, Ercole Brunetti⁵, Laura Bernardini⁴ and Giuseppe Novelli^1,2,7

¹Department of Biopathology, Tor Vergata University, Rome, Italy. ²Azienda Ospedaliera Universitaria Policlinico Tor Vergata, Rome, Italy. ³Technogenetics srl, Sesto San Giovanni, Milan, Italy. ⁴IRCCS-CSS San Giovanni Rotondo and CSS-Mendel, Rome, Italy. ⁵Ospedale San Pietro Fatebenefratelli, Rome, Italy. ⁶Department of Preventive Medicine, Harlyne Norris Research Tower, University of Southern California, Los Angeles, CA. ⁷Fondazione Livio Patrizi, Rome, Italy.  

Abstract

We designed a targeted-array called GOLD (Gain or Loss Detection) Chip consisting of 900 FISH-mapped non-overlapping BAC clones spanning the whole genome to enhance the coverage of 66 unique human genomic regions involved in well known micro-deletion/microduplication syndromes. The array has a 10 Mb backbone to guarantee the detection of the aneuploidies, and has an implemented resolution for telomeres, and for regions involved in common genomic diseases. In order to evaluate clinical diagnostic applicability of GOLDChip, analytical validity was carried-out via retrospective analysis of DNA isolated from a series of cytogenetically normal amniocytes and cytogenetically abnormal DNA obtained from cultured amniocytes, peripheral blood and/or cell lines. We recruited 47 DNA samples corresponding to pathologies with significant frequencies (Cri du Chat syndrome, Williams syndrome, Prader Willi/Angelman syndromes, Smith-Magenis syndrome, DiGeorge syndrome, Miller-Dieker syndrome, chromosomes 13, 18 and 21 trisomies). We set up an experimental protocol that allowed to identify chromosomal rearrangements in all the DNA samples analyzed. Our results provide evidence that our targeted BAC array can be used for the identification of the most common microdeletion syndromes and common aneuploidies.