New technique can track down causes of rare genetic diseases: Study

Researchers have invented a new technique in genomics to track down the causes of rare genetic diseases like muscular dystrophies.

For the new technology, the researchers, including those from Scripps Research Institute in the US, applied the fact that each person inherited two copies of every gene, or alleles -- one from the mother and another from the father.

In the new method, described in the journal Science, the researchers detected the activity levels of maternal and paternal alleles across the genome to determine when the activity of an allele was outside the normal range to be a plausible cause of disease.

"Adding this method to our toolkit should allow us to detect the causes of rare genetic diseases for some of the cases in which standard methods fail," said study first author Pejman Mohammadi from Scripps Research Institute.

Usually, to reveal the cause of rare genetic diseases like muscular dystrophies, the researchers said that the genes and their products from affected people and their family members were sequenced.

They added that this was done only if the disease-driving gene mutations were obvious ones resulting in either missing or severely truncated proteins.

Mohammadi said that at least half of all rare genetic diseases had more subtle causes that cannot be detected using the usual methods.

Mohammadi and his team used data on how genes coded for proteins to detect differences in the activity levels of maternal and paternal alleles.

The researchers said that many rare genetic diseases resulted from DNA mutations affecting the copy of a gene from one of the parents.

The study noted that comparing the activity of maternal and paternal alleles was a more sensitive method than comparing one person's gene activity to another's.

This, the researchers said was because any two people differ in many other complicated factors that affected gene activity, not just their genetic backgrounds.

"Even if you had an identical twin, the fact that the twin ate a burger this morning and you didn't would create differences between you in the activity levels of many genes," Mohammadi said.

The new technique -- called ANEVA-DOT (analysis of expression variation--dosage outlier test) -- can be used to identify a handful of genes in each individual with apparently abnormal expression levels in one allele, the study said.

"It might tell you there are 10 or 20 genes with allele activity levels that are way off, and you can then follow up to determine which of those is causing the disease--but compared with other methods, it cuts down dramatically the number of genes you have to analyze in that way," Mohammadi said.

The researchers said that they successfully detected the disease-linked genes in cases where there was already a diagnosis, and an expected major imbalance in allele activity.

Using the ANEVA-DOT technique, they also uncovered a short list of plausible disease-linked, muscle-related genes.