Discovering disease-causing mutations
For many years, it was expected that the majority of disease-causing gene mutations would occur in the exons of genes, which code for proteins. However, in recent years, researchers have discovered that over 60% of disease-causing gene mutations occur in splice sites, which are involved in RNA splicing. As the majority of disease-causing mutations occur within splice sites, the ability to target splicing mutations is paramount for precision medicine.
The S&S algorithm is used to discover splice site mutations, and predict their consequences in disease-causing genes. The algorithm pinpoints the effects of splice site mutations such as exon skipping and cryptic splice site activation, all of which can lead to disease. Clinical and research institutions use the S&S algorithm to predict the effects of mutations found in real splice sites as well as cryptic splice sites that occur deep within introns, thereby uncovering the causes of countless diseases.
OVER 60% OF DISEASE-CAUSING GENE MUTATIONS AFFECT THE SPLICING PROCESS AND CAN BE DISCOVERED WITH THE S&S ALGORITHM
S&S has been used to discover disease-causing gene mutations in numerous diseases, including the following:
Cancer
- Breast Cancer
- Ovarian Cancer
- Colorectal Cancer
- Leukemia
- Head And Neck Cancers
- Prostate Cancer
- Retinoblastoma
- Squamous Cell Carcinoma
- Gastrointestinal Cancer
- Melanoma, Liver Cancer
- Lynch Syndrome
- Skin Cancer
- Neurofibromatosis
- Gastric Cancer
Non Cancer
- Diabetes
- Obesity
- Neurological Disorders
- Marfan Syndrome
- Hypertrophic Cardiomyopathy
- Eye Disorders
- Muscular dystrophy
- Thyroid disorders
- Neuro-degenerative diseases
- Liver disorders
- Bardet-Biedl Syndrome
- Odontogenesis Diseases
- Beta-Ketothiolase Deficiency
- Inherited Retinal Diseases
Genome Explorer®: A comprehensive platform to discover disease genes using the S&S algorithm
Genome Explorer is a clinical genomics platform that incorporates the S&S algorithm and several additional algorithms developed by Genome International. It is fully automated by the touch of a button, and easy to use by clinicians and clinical researchers to discover genes in any disease.
Genome Explorer enables the discovery of genes causing disease and drug response phenotypes in patients at the point of care. It also provides the ability to discover new genes and mutations that cause different diseases by the analysis of patient cohorts. Similarly, Genome Explorer allows researchers to find the drug response genes in clinical trials for personalized drug development.
Click here to learn about Genome Explorer.
For decades, the field of biology and medicine has been thinking that mutations in the coding sequence regions (CDS) of genes are responsible for the vast majority of diseases. In contrast, Dr. Senapathy predicted that the majority of disease-causing mutations occur outside of the CDS in genes. Corroborating his predictions, it is now recognized that >60% of all disease-causing mutations in patients with any disease are caused by mutations in splice sites.
THE STRUCTURE OF A HUMAN GENE
The clinical field expected that 90% of disease-causing mutations occur in coding regions. In contrast, Dr. Senapathy found that more than 90% of all diseases are caused by mutations outside of coding regions.
Dr. Senapathy invented the Shapiro-Senapathy algorithm to predict splice sites in genes, and discover the mutations that occur within them that cause almost all human diseases and the diseases of all animals and plants. It is the most widely used algorithm for identifying disease-causing mutations around the world, and is the top clinical genomics algorithm.
To date, numerous studies on various diseases and patient cohorts around the world have been carried out based on the S&S algorithm, resulting in more than 6,000 peer-reviewed publications. It is currently used in hospitals and clinical institutions on a daily basis in their molecular diagnostics laboratories, through several web tools developed by scientists in various institutions.
Discovering the mechanism of disease:
Exon Skipping caused by a donor mutation in the gene MLH1 leading to colorectal cancer.
Using the S&S algorithm, it was discovered that a mutation in the donor splice site in exon 8 led to the skipping of the exon 8. The mRNA thus lacks the sequence corresponding to exon 8 (as shown in the figure). This causes a frame shift in the mRNA coding sequence at amino acid position 226, leading to premature protein truncation at amino acid position 233. This defective mutated protein has led to colorectal cancer in the patient.