Massively parallel sequencing, aCGH, and RNA-Seq technologies provide a comprehensive molecular diagnosis of Fanconi anemia.

摘要: Current methods for detecting mutations in Fanconi anemia (FA)–suspected patients are inefficient and often miss mutations. We have applied recent advances DNA sequencing genomic capture to the diagnosis of FA. Specifically, we used custom molecular inversion probes or TruSeq-enrichment oligos sequence FA related genes, including introns, from 27 samples International Anemia Registry at The Rockefeller University. was complemented with array comparative hybridization (aCGH) RNA (RNA-seq) analysis. aCGH identified deletions/duplications 4 different genes. RNA-seq analysis revealed lack allele specific expression associated a deletion splicing defects caused by missense, synonymous, deep-in-intron variants. combination TruSeq-targeted capture, aCGH, enabled us identify complementation group biallelic germline all families: FANCA (7), FANCB (3), FANCC FANCD1 (1), FANCD2 FANCF (2), FANCG FANCI FANCJ FANCL (3). cause Ashkenazi Jewish (AJ) ancestry, 2 novel AJ ancestry. describe here strategy efficient