Unlocking Mendelian disease using exome sequencing 英文参考文献.docVIP

Gilissen et al. Genome Biology 2011,12:228 /2011/12/9/228 REVIEW Unlocking Mendelian disease using exome sequencing Christian Gilissen*, Alexander Hoischen, Han G Brunner and Joris A Veltman straightforward follow-up by Sanger sequencing [9]. For Abstract example, genome-wide single nucleotide polymorphism analysis in a large Dutch pedigree with autosomal- dominant familial exudative vitreoretinopathy (FEVR, MIM 613310), a retinal disorder, identi?ed a linkage peak of about 40 Mb on chromosome 7, containing more than 300 genes [10]. Even after adding linkage data from a second FEVR family the region was still too large for straightforward disease-gene identi?cation, and Sanger Exome sequencing is revolutionizing Mendelian disease gene identication. This results in improved clinical diagnosis, more accurate genotype-phenotype correlations and new insights into the role of rare genomic variation in disease. e identi?cation of the causative mutation for a sequencing of a few candidate genes did not identify Mendelian disease enables molecular diagnosis and causative mutations. Next generation sequencing (NGS) carrier testing in the patient and his or her family. is is of great importance for patient management and family counseling, and serves as a starting point for therapeutic interventions [1]. Furthermore, the identi?cation of has the potential to identify all kinds of genetic variation at base-pair resolution throughout the human genome in a single experiment. is can be performed much faster and more cost e?ciently than with traditional techniques (the sequencing of a genome by traditional techniques needed many years and cost millions of dollars, whereas NGS technology can sequence a genome for less than $7,000 and within a week [11]). is enables the detailed genomic analysis of large numbers of patients [12]. In the Mendelian