Article

IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23.

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98104, USA.
The American Journal of Human Genetics (Impact Factor: 11.2). 06/2009; 84(5):692-7. DOI: 10.1016/j.ajhg.2009.04.008
Source: PubMed

ABSTRACT We have established strong linkage evidence that supports mapping autosomal-dominant sensory/motor neuropathy with ataxia (SMNA) to chromosome 7q22-q32. SMNA is a rare neurological disorder whose phenotype encompasses both the central and the peripheral nervous system. In order to identify a gene responsible for SMNA, we have undertaken a comprehensive genomic evaluation of the region of linkage, including evaluation for repeat expansion and small deletions or duplications, capillary sequencing of candidate genes, and massively parallel sequencing of all coding exons. We excluded repeat expansion and small deletions or duplications as causative, and through microarray-based hybrid capture and massively parallel short-read sequencing, we identified a nonsynonymous variant in the human interferon-related developmental regulator gene 1 (IFRD1) as a disease-causing candidate. Sequence conservation, animal models, and protein structure evaluation support the involvement of IFRD1 in SMNA. Mutation analysis of IFRD1 in additional patients with similar phenotypes is needed for demonstration of causality and further evaluation of its importance in neurological diseases.

0 Bookmarks
 · 
86 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper discusses a feedback control method for incompletely restrained wire-suspended mechanisms. The incompletely restrained wire-suspended mechanism has a merit that it enables three dimensional positioning and orientating of suspended object with simple mechanism using a small number of wires. However it also has a drawback that the manipulated object is easy to swing as seen in overhead crane which is one of the simplest incompletely restrained mechanism. For this reason, anti-sway control method for incompletely restrained type mechanisms is needed. A key point of our method is exact linearization using inverse dynamics of the system. Feedback control method with exact linearization and measuring method for the suspended object are presented, and effectiveness of proposed methods are shown by an experiment.
    Intelligent Robots and Systems, 2002. IEEE/RSJ International Conference on; 02/2002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Massively parallel sequencing has enabled the rapid, systematic identification of variants on a large scale. This has, in turn, accelerated the pace of gene discovery and disease diagnosis on a molecular level and has the potential to revolutionize methods particularly for the analysis of Mendelian disease. Using massively parallel sequencing has enabled investigators to interrogate variants both in the context of linkage intervals and also on a genome-wide scale, in the absence of linkage information entirely. The primary challenge now is to distinguish between background polymorphisms and pathogenic mutations. Recently developed strategies for rare monogenic disorders have met with some early success. These strategies include filtering for potential causal variants based on frequency and function, and also ranking variants based on conservation scores and predicted deleteriousness to protein structure. Here, we review the recent literature in the use of high-throughput sequence data and its analysis in the discovery of causal mutations for rare disorders.
    Human Molecular Genetics 10/2010; 19(R2):R119-24. · 7.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We carried out analyses with the goal of identifying rare variants in exome sequence data that contribute to disease risk for a complex trait. We analyzed a large, 47-member, multigenerational pedigree with 11 cases of autism spectrum disorder, using genotypes from 3 technologies representing increasing resolution: a multiallelic linkage marker panel, a dense diallelic marker panel, and variants from exome sequencing. Genome-scan marker genotypes were available on most subjects, and exome sequence data was available on 5 subjects. We used genome-scan linkage analysis to identify and prioritize the chromosome 22 region of interest, and to select subjects for exome sequencing. Inheritance vectors (IVs) generated by Markov chain Monte Carlo analysis of multilocus marker data were the foundation of most analyses. Genotype imputation used IVs to determine which sequence variants reside on the haplotype that co-segregates with the autism diagnosis. Together with a rare-allele frequency filter, we identified only one rare variant on the risk haplotype, illustrating the potential of this approach to prioritize variants. The associated gene, MYH9, is biologically unlikely, and we speculate that for this complex trait, the key variants may lie outside the exome.
    Human Heredity 01/2012; 74(3-4):153-64. · 1.57 Impact Factor

Full-text (2 Sources)

View
6 Downloads
Available from
May 22, 2014