\ ALS Research \ Genetic contributors to motor neuron diseases
The recent discovery of a number of genes known to cause motor neuron diseases such as ALS has provided new insights into the mechanisms underlying motor neuron degeneration, according to a recent article published in Nature Reviews Genetics.
In their review, Canadian researchers Patrick Dion, PhD, Hussein Daoud, PhD, and Guy Rouleau, MD, PhD, summarize the known genetic contributors to ALS and outline strategies for identifying subtle genetic variants that might work in combination to increase susceptibility.
Roughly 5-10 percent of ALS cases have a family history (familial ALS), but the vast majority of cases are sporadic and the cause is unknown. While heritable genetic defects resulting in familial ALS have provided valuable information about disease mechanisms, they only explain a fraction of all cases.
But increasingly, studies are implicating genetic factors in sporadic cases too. Recently, mutations in genes such as TAR DNA-binding protein (TDP-43) and fused in liposarcoma (FUS) have been identified in both familial and sporadic cases.
Many of the known genetic contributors to ALS can be separated into “functional classes,” the authors report, based on their roles within the cells of the nervous system. Pathways involved in RNA processing – an intermediate step between genes and the proteins they encode; axonal transport – the means by which cellular components are delivered to where they’re needed; and mitochondrial function (an essential source of energy for cellular processes), are disrupted by the genetic defects.
While genetics contribute significantly to the risk for ALS, factors that are environmental – such as toxins; epigenetic (ie., leading to changes in gene expression independent of mutations); or physical – such as injuries or stresses resulting from personal activities, are also suspected to confer susceptibility.
Studies with both epidemiological and genetic components are needed to tease out the various contributors to what the authors call “this heterogeneous disease.”
While ALS is the most common motor neuron disease of adulthood, several others with similar features exist – including hereditary spastic paraplegia, primary lateral sclerosis and spinal muscular atrophy. The authors provide an overview of the genetic contributors to these related disorders, several of which fall into the same functional classes described above. They conclude that genes involved in RNA processing, axonal transport and mitochondrial function should be prioritized as candidate genes in future genetic studies in ALS.
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Genetic contributors to motor neuron diseases
By: Katie Moisse, PhDThe recent discovery of a number of genes known to cause motor neuron diseases such as ALS has provided new insights into the mechanisms underlying motor neuron degeneration, according to a recent article published in Nature Reviews Genetics.
In their review, Canadian researchers Patrick Dion, PhD, Hussein Daoud, PhD, and Guy Rouleau, MD, PhD, summarize the known genetic contributors to ALS and outline strategies for identifying subtle genetic variants that might work in combination to increase susceptibility.
Roughly 5-10 percent of ALS cases have a family history (familial ALS), but the vast majority of cases are sporadic and the cause is unknown. While heritable genetic defects resulting in familial ALS have provided valuable information about disease mechanisms, they only explain a fraction of all cases.
But increasingly, studies are implicating genetic factors in sporadic cases too. Recently, mutations in genes such as TAR DNA-binding protein (TDP-43) and fused in liposarcoma (FUS) have been identified in both familial and sporadic cases.
Many of the known genetic contributors to ALS can be separated into “functional classes,” the authors report, based on their roles within the cells of the nervous system. Pathways involved in RNA processing – an intermediate step between genes and the proteins they encode; axonal transport – the means by which cellular components are delivered to where they’re needed; and mitochondrial function (an essential source of energy for cellular processes), are disrupted by the genetic defects.
While genetics contribute significantly to the risk for ALS, factors that are environmental – such as toxins; epigenetic (ie., leading to changes in gene expression independent of mutations); or physical – such as injuries or stresses resulting from personal activities, are also suspected to confer susceptibility.
Studies with both epidemiological and genetic components are needed to tease out the various contributors to what the authors call “this heterogeneous disease.”
While ALS is the most common motor neuron disease of adulthood, several others with similar features exist – including hereditary spastic paraplegia, primary lateral sclerosis and spinal muscular atrophy. The authors provide an overview of the genetic contributors to these related disorders, several of which fall into the same functional classes described above. They conclude that genes involved in RNA processing, axonal transport and mitochondrial function should be prioritized as candidate genes in future genetic studies in ALS.
| Posted On: Wednesday, January 13, 2010 Modified: Wednesday, January 13, 2010 Category: ALS Research Posted By: |