Cause Of Lou Gehrig's Disease, Amyotrophic Lateral Sclerosis (ALS) Linked To Chromosome Nine

Cause Of Lou Gehrig's Disease, Amyotrophic Lateral Sclerosis (ALS) Linked To Chromosome Nine
Editor's Choice
Main Category: Muscular Dystrophy / ALS
Also Included In: Neurology / Neuroscience
Article Date: 31 Aug 2010 - 1:00 PDT


Two substantial studies, and articles published by The Lancet Neurology have confirmed that variations to the genes located on chromosome number nine may contribute to the development of front temporal dementia and also ALS, amyotrophic lateral sclerosis which is commonly known as Lou Gehrig's Disease. Lou Gehrig, an American baseball player with the New York Yankees, was diagnosed with ALS June 19, 1939 on his 36th birthday and the condition has bared his name ever since.

The attempt to isolate the genetic cause of ALS still remains ambiguous. As only between five and ten percent of ALS cases are hereditary, a few genes have been traced back to ALS, but experts only find this is the case in a small amount of familial cases.

GWAS or Genome-wide Association on Studies have identified a few probable gene traces, but independent studies have been unable to confirm these findings. However, in 2006, a connection between hereditary ALS and specifically chromosome nine, was detected in Scandinavia. Finland in particular is a well suited location for a GWAS of ALS, because the incidence of the disease is one of the highest in the world. Because the Finnish have such a similar genetic makeup, such studies are more accurate due to the reduction of genetic variability. The National Institutes of Health's Bryan Tanor performed a Genome-wide Association Study in Finland for this reason.

Tanor's study found 318 167 DNA variations known as single nucleotide polymorphisms (SNPs). These variations were analyzed in the genome of each of the 405 patients with ALS (93 familial and 312 sporadic) and 497 controls.

Two genetic variations that contribute to risk of ALS were revealed. First, the SOD1 gene, which has been commonly traced as a cause of ALS, on chromosome 21q (rs13048019). The second trace was on chromosome 9p (rs3849942). More than 70% of patients with a family history of ALS displayed genetic variations in Finland.

The original authors of the study stated:


"The chromosome 9p21 locus is a major cause of familial ALS in the Finnish population."


Ammar Al-Chalabi from King's College London also discovered a link with chromosome 9. They started by examining the DNA of 599 patients with sporadic ALS and 4144 controls from the UK. Genetic markers (rs3849942 and rs2814707) proved to be directly associated with sporadic ALS, both which are located on chromosome 9p.

Ammar Al-Chalabi 's team performed a joint analysis of UK samples with an additional 4312 patients with ALS, and 8425 controls from seven other countries. This study was the largest of its kind in history. Chromosome 9p21.2 was the only gene associated with frontotemporal dementia.

The authors of this second Lancet Neurology paper concluded:


We have found strong evidence of a genetic association of two single SNPs on chromosome 9 with sporadic ALS, in line with findings from previous independent GWAS of ALS University of Montreal's Guy Rouleau : "Although the results presented here must be interpreted with caution, both studies identified a linkage disequilibrium block in the chromosome 9p21 locus, suggesting that a variant in this genomic interval might have a role in ALS and possibly frontotemporal dementia. However, because patients with familial chromosome 9p-linked ALS-frontotemporal dementia do not share a common haplotype, multiple variations, and thus multiple founders, are probably involved.


"Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study"
Hannu Laaksovirta, Terhi Peuralinna, Jennifer C Schymick, Sonja W Scholz, Shaoi-Lin Lai, Liisa Myllykangas, Raimo Sulkava, Lilja Jansson, Dena G Hernandez, J Raphael Gibbs, Michael A Nalls, David Heckerman, Pentti J Tienari, Bryan J Traynor
Lancet Neurology Published Online August 31, 2010 DOI:10.1016/S1474-4422(10)70184-8

Written By: Sy Kraft
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Cause Of Lou Gehrig's Disease, Amyotrophic Lateral Sclerosis (ALS) Linked To Chromosome Nine