Tuesday, August 19, 2014

New software enables detection of disease associated insertion deletion mutations

Insertion deletion mutations (indel mutations or indels) can have a profound effect on biological function. As their name suggests this is when genetic sequence is either added or removed.  The effect of these mutations is especially evident when these mutations occur in a protein coding region as they can lead to the production of proteins that are truncated or otherwise altered so that function is severely impacted. However, these indel mutations can vary in length, from 1 base pair to thousands. Furthermore the sequence that is inserted or deleted can be highly variable.The variability of indels has made them difficult to detect within the genome, until now!

Photograph of CSHL in the fall of 2008
by AdmOxalate
A group of scientists at Cold Spring Harbor Labs have developed and used a new software program called Scalpel to precisely see where indels are causing cuts in the genome. The results of their work are published in a recent issue of the journal Nature Methods in an article entitled: 'Accurate de novo and transmitted indel detection in exome-capture data using microassembly'.



The group used Scalpel on a genome database produced from families in which one child suffered from autism and the rest of the family is unaffected. This approach allowed them to identify indels that likely disupt genes in autistic children.

The scientist are now seeking to apply Scalpel more broadly and are collaborating with any scientists, such as cancer biologists, that are looking for indels.

Some material for this post was obtained from the Science Daily article: A shift in the code: New method reveals hidden genetic landscape

Original Article citation: Giuseppe Narzisi, Jason A O'Rawe, Ivan Iossifov, Han Fang, Yoon-ha Lee, Zihua Wang, Yiyang Wu, Gholson J Lyon, Michael Wigler, Michael C Schatz. Accurate de novo and transmitted indel detection in exome-capture data using microassemblyNature Methods, 2014