|
|
|
| Home » Diagnostics » Research |
Diagnostics
|
Areas of Research
|
1. Identification of novel genes for single gene disorders
2. Molecular genetic analysis for lysosomal storage disorders
3. Characterization of chromosomal rearrangements in human genetic disorders
|
Research Interests
Human Exome Sequencing to Identify Novel Genes for Mendelian Disorders
Indian Exome Database
Single gene disorders are rare by themselves but collectively they are an important cause of morbidity and mortality. The identification of genes for single gene disorders has value, not only in prenatal diagnosis and genetic counselling of affected families, but also in basic research towards understanding gene functions and mechanisms of disease. This in turn can help to improve our knowledge regarding the function of the proteins involved and development of new therapeutic options for both single gene and common multifactorial disorders. Till date about 2900 genes causing single gene disorders have been identified but still a large number remains to be characterized. The classical methods of gene identification include chromosomal breakpoint mapping, linkage analysis and homozygosity mapping. Although these methods are robust and have resulted in identification of over 2900 genes, there are certain limitations of these methods. The classical methods are laborious and require multiple families with multiple affected individuals, thus they cannot be used for single gene disorders occurring sporadically or exhibiting phenotypic heterogeneity. On the other hand, the availability of massively parallel sequencing technologies have made it possible to identify gene for a particular disease using just a few affected individuals. We employ whole exome sequencing, to identify mutations in such affected families. India has a rich resource of patients with single gene diseases, owing to the large population and practice of consanguineous marriages. It is expected that these studies will not only enable capacity building in the country in the use of these next generation technologies, but also will provide new insights into human gene functions.
Molecular genetic analysis for lysosomal storage disorders
Lysosomal storage disorders are a heterogeneous group of disorders associated with specific lysosomal enzyme deficiency. Enzyme replacement therapy (ERT) is available for at least 5 of these disorders, namely Gaucher disease, Fabry disease, Mucopolysaccharidosis type I and VI, and Pompe disease. Phase II trials are underway for Niemann Pick disease. Our study aims to characterize the clinical features, biochemical parameters and molecular defects for few of these disorders. The results would form the basis for revealing the spectrum of mutations for these disorders in the Indian population which will in turn help in better diagnosis of carriers for these disorders and accurate prenatal diagnosis. At present the diagnosis and prenatal diagnosis of these disorders is primarily based on enzyme assay, which has a number of disadvantages. There is a large amount of overlap in enzyme levels among carriers and normal people; hence it is very difficult to detect carriers by enzyme assay. Therefore mutation detection is imperative for carrier detection. In addition, the data regarding mutations will be helpful in genotype phenotype studies in these disorders. Further, the knowledge regarding mutations in Indian patients will help in establishing testing for these disorders as a service to the patients. We conduct detailed clinical assessment of patients followed by screening tests and specific enzyme assay for following disorders—Niemann Pick disease, Mucopolysaccharidosis Type VI, Mucolipidosis Type I, II, III, and Farber disease. After confirmation of diagnosis, mutation analysis is performed by sequencing the respective genes. Genotype phenotype analysis is carried out to assess the association of certain genotypes with clinical features, enzyme activity, etc
Cloning, Characterization and analysis of chromosomal rearrangements in human genetic disorders
Chromosomal abnormalities and gene mutations can lead to human genetic disorders. Structural rearrangements alter the genome architecture and may result in human disease phenotypes. These alterations can be termed as genomic disorders. The patients with translocations and inversions often have breakpoints located within the disease gene, or very close to it. In order to identify the disease gene, breakpoints should be characterized and if any gene is disrupted by rearrangement then it is considered as a candidate gene. Cloning their breakpoint can provide the quickest route to identifying the disease gene. The identification of genes involved in human disease is important to understand the pathology of the disease, further it often provides new insight into normal human development and biology. The identification of genes involved in human disease is important to understand the disease. For the identification of new genes, chromosomal rearrangements associated with a disease are essential. Thus, characterizing those isolated chromosomal rearrangements would help us in the identification of novel genes. This project deals with the molecular characterization of chromosomal breakpoints associated with specific clinical phenotypes. Basically, we are following positional cloning approach for identification of chromosomal breakpoints. These modern techniques will help to study the causes of chromosomal abnormalities and thus also will help to set up effective diagnostic tool for better investigations and genetic counseling. Implementing these modern technologies will be of great help in our country where there is a need to improve the quality of diagnosis and genetic counseling.
|
|
|
Last updated on : Thursday, 20th September, 2018.
|
|
|
|
|
