Molecular diagnosis for heterogeneous genetic diseases with high-throughput DNA sequencing applied to retinitis pigmentosa

BACKGROUND:
The genetic heterogeneity of many Mendelian disorders, such as retinitis pigmentosa which results from mutations in over 40 genes, is a major obstacle to obtaining a molecular diagnosis in clinical practice. Targeted high-throughput DNA sequencing offers a potential solution and was used to develop a molecular diagnostic screen for patients with retinitis pigmentosa.
METHODS:
A custom sequence capture array was designed to target the coding regions of all known retinitis pigmentosa genes and used to enrich these sequences from DNA samples of five patients. Enriched DNA was subjected to high-throughput sequencing singly or in pools, and sequence variants were identified by alignment of up to 10 million reads per sample to the normal reference sequence. Potential pathogenicity was assessed by functional predictions and frequency in controls.
RESULTS AND CONCLUSIONS:
Known homozygous PDE6B and compound heterozygous CRB1 mutations were detected in two patients. A novel homozygous missense mutation (c.2957A?T; p.N986I) in the cyclic nucleotide gated channel ß1 (CNGB1) gene predicted to have a deleterious effect and absent in 720 control chromosomes was detected in one case in which conventional genetic screening had failed to detect mutations. The detection of known and novel retinitis pigmentosa mutations in this study establishes high-throughput DNA sequencing with DNA pooling as an effective diagnostic tool for heterogeneous genetic diseases.

Home curation versus teenage photography: Photo displays in the family home

In this paper we report an empirical study of the photographic portrayal of family members at home. Adopting a social psychological approach and focusing oil intergenerational power dynamics, our research explores the use of domestic photo displays in family representation. Parents and their teenagers from eight families in the south of England were interviewed at home about their interpretations of both stored and displayed photos within the home. Discussions centred on particular photographs found by the participants to portray self and family in different ways. The findings show that public displays of digital photos are still curated by mothers of the households, but with more difficulty and less control all with analogue photos. In addition, teenagers both contribute and comply with this curation within the home, whilst at the same time developing additional ways of presenting their families and themselves online that are 'unsupervised' by the curator. We highlight the conflict of interest that is at play within teen and parent practices and consider the challenges that this presents for supporting the representation of family through the design of photo display technology. (C) 2009 Elsevier Ltd. All rights reserved.

Teaching and learning technologies in Higher Education: Applied behaviour analysis and autism.

Professionals on both international and national levels who work with children with autism are expressing the need for graduate-level training in applied behaviour analysis. The implementation of effective instruction in higher education for professionals working with children with autism and their families is a complex undertaking: the learner needs to acquire an understanding of the principles and procedures of applied behaviour analysis and also adapt this knowledge to the learning prerequisites of individuals with autism. In this paper we outline some current thinking about adult education and blended learning technologies and then describe and illustrate with examples emerging possibilities of multimedia technology in the development of teaching materials. We conclude that synergies between graduate-level curriculum requirements, knowledge of adult learning, and communication technology are necessary to establish comprehensive learning environments for professionals who specialize in autism intervention.