Exome sequencing reveals pathogenic mutations in 91 strains of mice with Mendelian disorders.
نویسندگان
چکیده
Spontaneously arising mouse mutations have served as the foundation for understanding gene function for more than 100 years. We have used exome sequencing in an effort to identify the causative mutations for 172 distinct, spontaneously arising mouse models of Mendelian disorders, including a broad range of clinically relevant phenotypes. To analyze the resulting data, we developed an analytics pipeline that is optimized for mouse exome data and a variation database that allows for reproducible, user-defined data mining as well as nomination of mutation candidates through knowledge-based integration of sample and variant data. Using these new tools, putative pathogenic mutations were identified for 91 (53%) of the strains in our study. Despite the increased power offered by potentially unlimited pedigrees and controlled breeding, about half of our exome cases remained unsolved. Using a combination of manual analyses of exome alignments and whole-genome sequencing, we provide evidence that a large fraction of unsolved exome cases have underlying structural mutations. This result directly informs efforts to investigate the similar proportion of apparently Mendelian human phenotypes that are recalcitrant to exome sequencing.
منابع مشابه
Whole Exome Sequencing Reveals a BSCL2 Mutation Causing Progressive Encephalopathy with Lipodystrophy (PELD) in an Iranian Pediatric Patient
Background: Progressive encephalopathy with or without lipodystrophy is a rare autosomal recessive childhood-onset seipin-associated neurodegenerative syndrome, leading to developmental regression of motor and cognitive skills. In this study, we introduce a patient with developmental regression and autism. The causative mutation was found by exome sequencing. Methods: The proband showed a gener...
متن کاملExome sequencing covers >98% of mutations identified on targeted next generation sequencing panels
BACKGROUND With the expanded availability of next generation sequencing (NGS)-based clinical genetic tests, clinicians seeking to test patients with Mendelian diseases must weigh the superior coverage of targeted gene panels with the greater number of genes included in whole exome sequencing (WES) when considering their first-tier testing approach. Here, we use an in silico analysis to predict ...
متن کاملCRB1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum
Background: Leber congenital amaurosis (LCA) is a rare inherited retinal disease causing severe visual impairment in infancy. It has been reported that 9-15% of LCA cases have mutations in CRB1 gene. The complex of CRB1 protein with other associated proteins affects the determination of cell polarity, orientation, and morphogenesis of photoreceptors. Here, we report three novel pathogenic varia...
متن کاملExome Sequencing of Ion Channel Genes Reveals Complex Profiles Confounding Personal Risk Assessment in Epilepsy
Ion channel mutations are an important cause of rare Mendelian disorders affecting brain, heart, and other tissues. We performed parallel exome sequencing of 237 channel genes in a well-characterized human sample, comparing variant profiles of unaffected individuals to those with the most common neuronal excitability disorder, sporadic idiopathic epilepsy. Rare missense variation in known Mende...
متن کاملNF1 Mutations Analysis Using Whole Exome Sequencing Technique in 11 Unrelated Iranian Families with Neurofibromatosis Type 1
Background Neurofibromatosis is an autosomal dominant disease. It affects one in 2,700 to 3,300 people. The main gene mutated in the disease is a tumor suppressor protein called neurofibromin. There are several categories, the most important of which is divided into two types of type I and type 2 neurofibromatosis. Here, we aimed to identify th...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Genome research
دوره 25 7 شماره
صفحات -
تاریخ انتشار 2015