About Careers Internship MedBlog Contact us
New Method to Identify Gene Mutations That Lead to Disease

New Method to Identify Gene Mutations That Lead to Disease

Font : A-A+

  • A research team from Brown University has developed a software that can be used to identify large sections of DNA, within a relatively short span of time.
  • It is used to identify splicing errors that occur during synthesis of proteins from DNA.
  • Such a mass analyzing tool will be effective in screening for mutations among patients, paving the way for precision medicine.

A genetic mutation is one in which there is a permanent change in the DNA sequence of a gene that causes the sequence to be very different from what is present in most people. Dr. William Fairbrother from Brown University states that while it is no longer difficult to identify gene variations in people, it is important to ascertain the effect of these mutations on health.


The study by Dr. Fairbrother and colleagues, published in the journal Nature Genetics, involved the use of a new technique called "MaPSy", where about 5,000 mutations were sorted and which identified nearly 500 mutations that were caused due to an error in the processing of genes by cells. The new technique could also be used to identify the reason behind the error.

Precision Medicine

Dr. Fairbrother stated that it was possible to obtain multiple variants from individuals and all these variants could be sequenced. However, it is important to identify which variant led to the development of disease. This would be the starting point for precision medicine as the response to therapy could be ascertained from the variations carried in the gene sequence.

Gene Splicing:

Gene splicing is a modification that occurs post transcription, in which a single gene could code for various proteins. It is the process by which sections of DNA that do not code for any protein are removed. Dr. Fairbrother has allocated the necessary resources to develop newer methods as well as tools, including biophysical systems similar to MaPSy and new software to study gene splicing. This is because, while the instructions carried by the gene are necessary for the synthesis of protein, gene splicing could also play an important role in the development of diseases.

In a simple gene variation, a single amino acid may be altered to another one; however, in gene splicing, 40 to 50 amino acids could be removed due to a mutation. The significance of these mutations could therefore be more pronounced.


Spliceman is a free web based software that was developed by Dr. Fairbrother's lab in 2012 and which can be used to identify mutations that are likely to result in errors in splicing. The scientists who were involved in the development of this software won the CLARITY contest, in which the entire genome of three families had to be sequenced and the mutations that led to disease in the children were identified.


MaPSY stands for 'Massively Parallel Splicing Assay' that was used for rapidly screening the gene splicing effects of 4,964 variations in the Human Gene Mutation Database (HGMD) that caused genetic disorders. This screening tool was developed by Dr.Fairbrother along with Rachel Soemedi andKamil Cygan.

How Does MaPSy work?

The mechanism of action of MaPSY is by generating "pooled" artificial genes that were made up of
  • Normal genes and
  • Disease causing variations of genes
Thousands of these artificial genes were then studied under in-vivo conditions as well as in in-vitro conditions.

In-vivo study:

The "pooled" artificial genes were introduced into living cells to study how often the normal or mutant genes wereprocessed successfully.

In-vitro Study:

The splicing machinery was removed from the nucleus of the cell and the "pooled" synthesized RNA was introduced to determine how often the genes were processed.

The results of the study were
  • Nearly 18 % of the Human Genome Mutation Database mutations were associated with splicing errors in the in-vivo study.
  • Nearly 24 % of the Human Genome Mutation Database mutations were associated with splicing errors in the in-vitro study.
The study identified that nearly 10% of mutations produced splicing errors in both the in-vitro study as well as the in-vivo study. This implied that there was a strong likelihood that the mutations were indeed sources of errors during splicing.

Predicting Diseases

The study helped in identifying mutations that were associated with the development of diseases, arising from splicing errors. Dr. Fairbrother and colleagues examined the sequence information and the splicing errors to identify the source of the different splicing error mutations. Combinations of genes that had a higher likelihood of developing splicing errors were identified; this was used to predict errors and even 'fix' them.

COL1A2 gene Mutation

In an example that was highlighted in the study, a particular variation in COL1A2, a gene associated with collagen and bone growth, led to an unwanted binding site for a protein which blocks splicing. When this binding site was intervened in cells, the splicing process continued as normal.

Evidence from Patient Samples:

When tissue samples from patients were analyzed, it was found that there was evidence of splicing error as predicted by MaPSy. This technique could prove to be a powerful tool and can be used for characterization of variations in gene sequences associated with splicing errors.

References :
  1. What are single nucleotide polymorphisms (SNPs)? - (https://ghr.nlm.nih.gov/primer/genomicresearch/snp)

Source: Medindia

Citations   close


News A-Z
What's New on Medindia
Alarming Cesarean Section Trends in India - Convenience or Compulsion of Corporate Healthcare
Quiz on Low-Calorie Diet for Diabetes
World Heart Day in 2022- Use Heart for Every Heart
View all
Recommended Reading
News Archive
News Category

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
DNA Finger Printing Cystic Fibrosis McArdle Disease Weaver Syndrome Inherited Breast Cancer Syndromes Von Hippel-Lindau Disease / Rare Genetic Disorder How Do Viruses Mutate and Why Does it Matter? 

Most Popular on Medindia

Drug - Food Interactions Hearing Loss Calculator Calculate Ideal Weight for Infants Blood - Sugar Chart Accident and Trauma Care The Essence of Yoga Indian Medical Journals Blood Donation - Recipients Post-Nasal Drip Color Blindness Calculator
This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use

New Method to Identify Gene Mutations That Lead to Disease Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests