Database of chromosomal abnormalities

28 April 2009

Changes in chromosomal structure such as copy number variations (CNVs) in certain regions can be associated with a wide range of developmental disorders including forms of learning disability (LD). Clinical diagnosis can be supported by investigation of chromosomal abnormalities. Technologies such as array comparative genomic hybridisation (array-CGH) can assist in accurate diagnosis by rapid detection of copy number changes across the whole genome. However, along with identifying variations associated with particular phenotypes, this technology can also identify new variations of unknown significance, which may or may not be involved in the developmental disorder. The determination of the pathogenicity of these variants is complicated by the rarity or novel nature of many of the associated mutations, making correlations between observed variations with specific disease phenotypes difficult.

In order to facilitate the diagnosis of developmental disorders, an interactive web-based database was initiated in 2004 at the Wellcome Trust Sanger Centre - DECIPHER (Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources). This tool allows clinicians from around the world to maintain and share records of phenotype and chromosome rearrangements (with informed consent). A recent report in the American Journal of Human Genetics outlines DECIPHER’s role in clinical practice and genetic research and how it has benefited patients, clinicians and researchers [Firth H et al (2009) Am J Hum Genet. 84(4) 524-33]. The report describes the analysis tools available to those who use DECIPHER, as well giving examples of how it has been used through case studies. In addition, the report also describes its utility in the clinical evaluation of novel changes as well as it role in investigating gene function.

The database contains clinical information about chromosomal changes such as deletions, insertions, inversions and translocations from particular cases and displays this information on the human genome map. This allows identification of cases which share phenotypic and chromosomal characteristics, thereby leading to a greater understanding disorders and their underlying genetic cause. Currently, the database contains information on over 2000 cases from 100 centres. In addition, the database also catalogues chromosomal rearrangements identified in healthy individuals; excluding these non-pathological rearrangements aids identification of chromosomal changes genuinely associated with disease phenotypes. Along with aiming to increase medical and scientific knowledge about these chromosomal changes, the database also aims to improve medical care and genetic advice for individuals/families and facilitate research into the study of genes which affect human development and health.

Comment: A genetic diagnosis can be of great value to individuals and families for many reasons including optimal clinical management of the condition, genetic counselling and access to special needs services (see our website sections on Learning Disability: the interface with genetics and Evaluation of array-CGH for chromosomal abnormalities in clinical practice). The DECIPHER database, by facilitating information sharing among clinicians, is helping to improve medical understanding of and clinical support for individuals affected by developmental disorders arising from chromosomal abnormalities.

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