Transcriptional Impact of Rare and Private Copy Number Variants in XXXX .

@entity1 @entity19 @entity1699 @entity600 @entity471 @entity299 @entity4297
BACKGROUND: @entity1699 ( @entity1699 ) is a heterogeneous, lethal combination of @entity600 characterized by severe underdevelopment of left @entity299 , resulting in a univentricular circulation. The genetic determinants of this disorder are largely unknown. Evidence of copy number variants (CNVs) contributing to the genetic etiology of @entity1699 and other @entity4297 has been mounting. However, the functional effects of such CNVs have not been examined, particularly in cases where the variant of interest is found in only a single @entity1 . METHODS AND RESULTS: Whole-genome SNP microarrays were employed to detect CNVs in two @entity1 cohorts (N = 70 total) predominantly diagnosed with some form of nonsyndromic @entity1699 . We discovered 16 rare or private variants adjacent to or overlapping 20 genes associated with cardiovascular or premature lethality phenotypes in @entity19 knockout models. We evaluated the impact of selected variants on the expression of nine of these genes through quantitative PCR on cDNA derived from @entity1 heart tissue. Four genes displayed significantly altered expression in @entity1 with an overlapping or proximal @entity471 verses @entity1 without such CNVs. CONCLUSION: Rare and private genomic imbalances perturb transcription of genes that potentially affect cardiogenesis in a subset of nonsyndromic @entity1699 @entity1 . Clin Trans Sci 2015; Volume #: 1-8.
