The Service laboratories are fully equipped to provide a comprehensive diagnostic service, including chromosome analysis, fluorescence in situ hybridization (FISH), array-CGH and molecular genetic diagnosis for a wide range of disorders. The has led the way in deploying direct sequencing for mutation detection for routine service use, particularly for large genes including neurofibromatosis and tuberous sclerosis (TSC1 and TSC2) for which a national diagnostic service is provided. The laboratories provide over 3,000 chromosome analyses per year including for prenatal diagnosis and over 4,000 DNA diagnoses.
Research interests in the department include the detection and characterization of submicroscopic deletions by array-CGH and correlation with phenotype (Dr Firth and Dr Simonic) and participation in a variety of national cancer genetic studies (Dr Paterson). We are aiming to develop the portfolio of tests that the laboratory offers to compliment the research and clinical expertise surrounding us in Cambridge to provide better services for patients both at a local, national and international level. About 50% of the diagnostic workload in the Clinical Genetics department relates to the investigations and follow up of patients with learning disability, developmental delay, congenital malformations and abnormal fetal development. To improve the diagnostic yield for these patients and their families it is crucial to incorporate new technological developments such as microarray analysis into the diagnostic practice.
About 20% of DNA copy number changes detected using GeneChip 250K_Nsp array are deletions of <100 kb or duplications of <1 Mb in size encompassing predicted genes or OMIM genes with unknown functions and further work is required to elucidate their potential clinical significance. As part of the BRC/Genetics/Theme we aim to exploit the translational research potential of the microarray analysis and follow up all the unknown/novel DNA copy number changes. We are undertaking analysis of 3,000 WTCCC control samples to investigate which of the novel DNA copy number changes of unknown clinical significance represent rare copy number variants found in the normal population and which are novel, likely clinically significant abnormalities requiring further follow up on a sequence level. The analysis of the WTCCC data will generate an important resource for further diagnostic and research classification of detected DNA copy number changes.
Combined with both activities is a desire to improve the ability to interpret the likely functional consequences of genetic rearrangements.