Diagnosing rare diseases using RNA sequencing

From Stanford University by Hanae Armitage

Every person distills down to a script of DNA, and researchers are increasingly mining this genetic information to better inform care. Now, scientists have shown how RNA — an offshoot of DNA — is coming into its own as doctors sleuth out difficult-to-diagnose illnesses.

In a new study in Nature MedicineStephen Montgomery, PhD, a Stanford associate professor of pathology and of genetics, shows why the transcriptome, the collection of RNA molecules in a cell, is a crucial clue to help decipher the source of some rare diseases….

Right now with genome sequencing we can identify hiccups in the DNA, such as mutations, which are more broadly known as gene variants. But we all have a variety of these gene variants, and not all of them are bad; some don’t have any effect. With transcriptome sequencing, we’re able to see if those genes, variants and all, are functioning normally. Sometimes a gene that looks fine on the level of its DNA is actually malfunctioning, producing too much or too little protein, for instance. And we can detect this from the transcriptome.

So when evaluating a patient’s transcriptome, the two things that we’ve focused on have been the level of gene expression and how that level compares to healthy individuals, as well as something called splicing, which is how the transcript is pieced together to make the correct sequence of mRNA.

(read more…)

Frésard L et al. (2019) Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts. Nat Med [Epub ahead of print]. [abstract]

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