Copy number variations(CNVs)have increasingly been reported to cause,or predispose to,human ***,a large fraction of these CNVs have not been accurately characterized at the single-base-pair level,thereby hampering a b...
详细信息
Copy number variations(CNVs)have increasingly been reported to cause,or predispose to,human ***,a large fraction of these CNVs have not been accurately characterized at the single-base-pair level,thereby hampering a better understanding of the mutational mechanisms underlying CNV *** deficiency is due both to the inability of Sanger sequencing to characterize large CNV regions and to the inaccuracy of inferences drawn from whole genome sequencing *** employed a relatively straightforward composite pipeline,employing various methods including inference-based programs,to directly characterize CNVs to a single base-pair level of accuracy and reveal their associated *** the pipeline,we successfully characterized four novel CNVs involving two autosomal genes causing hereditary osteochondromas(EXT1,EXT2)and one X-linked gene(CLCN5)causing Dent disease,as well as 29 CNVs previously identified by inference from a cohort of Canadian autism spectrum disorder *** found that breakpoint flanking micro-mutations(within22 bp of the breakpoint)are present in a significant fraction(5/26;19%)of the deletion *** analysis also provided evidence that a recently described error-proneform of DNA repair(i.e.,repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genome)not only causes human genetic disease but also impacts on human genome *** investigation of the EXT1 duplication revealed that this genomic rearrangement had a duplication-inverted triplication-duplication structure,the inverted triplication being a 41-bp sequence synthesized from a nearby *** findings illustrate the importance of precise CNV breakpoint delineation for understanding the underlying mutational mechanisms and have implications for primer design in relation to the detection of deletion CNVs in clinical diagnosis.
暂无评论