Lyon wrote:I... but it now seems obvious that MS incidence is owed to "environmental predisposition" (as the only alternative to "genetic predisposition") and genetic factors, and possibly other environmental factors are secondary "triggers" (only after environmental predisposition could these triggers enable the MS process to begin).
Considering the situation, I don't see how anyone could make a logical argument for genetic predisposition
I think the key word here is "tendency", not a guarantee.pre·dis·po·si·tion –noun
1. the fact or condition of being predisposed: a predisposition to think optimistically.
2. Medicine/Medical. tendency to a condition or quality, usually based on the combined effects of genetic and environmental factors.
An identical twin of a person who has multiple sclerosis have a 25-percent chance of getting the disease
A population-based study of multiple sclerosis in twins.
[My paper] G C Ebers , D E Bulman , A D Sadovnick , D W Paty , S Warren , W Hader , T J Murray , T P Seland , P Duquette , T Grey
Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.
but familial clustering seems to be a secondary issue to the actual predisposition to the disease.tall, dark and handsome wrote:Because of "familial clustering" I am not so foolish as to think that genetics aren't involved in MS incidence
Although no specific gene for multiple sclerosis has been identified, several researchers have concluded that people with multiple sclerosis inherit certain regions on individual chromosomes more often than people without multiple sclerosis. Researchers are investigating the human leukocyte antigen (HLA) on chromosome 6, since the HLA patterns of multiple sclerosis patients appear to be different from those who do not have multiple sclerosis. Development of multiple sclerosis is likely to be influenced by the interactions of a number of genes, each of which (individually) has only a modest effect. Additional studies are needed to specifically pinpoint which genes are involved, determine their function, and learn how each gene's interactions with other genes and with the environment make an individual susceptible to multiple sclerosis. In addition to leading to better ways to diagnose multiple sclerosis, such studies should yield clues to the underlying causes of multiple sclerosis and, eventually, to better treatments or a way to prevent the disease.
A cluster of genes on chromosome six is the only one that plays a significant role in multiple sclerosis (MS), according to the most complete genetic study to date in the if disorder, presented at the 130th annual meeting of the American Neurological Association in San Diego.
"Our results confirm the strong role of the major histocompatibility complex genes in MS, and provides a definitive statement that no other region of the genome harbors a gene with a similar overall influence on MS genetics," said Jonathan Haines, Ph.D, of Vanderbilt University in Nashville, Tennessee, who presented on behalf of the International Multiple Sclerosis Genetics Consortium.
"A detailed examination of the major histocompatibility complex is critically important," said Haines, who suggests that this study may have profound implications for the future directions of MS genetics research.
The major histocompatibility complex (MHC) is a cluster of genes that play a critical role in the recognition of cells in the body as belonging to the body, i.e., not intruders such as bacteria or other pathogens.
When this system of recognition breaks down, the immune system may mistakenly launch an attack against cells, as happens in MS. Researchers believe that some genetic variations in MHC genes make people more susceptible to whatever environmental causes also contribute to MS.
Haines is one of the founders of an international team of researchers from many institutions that collected genetic data on 730 families with more than one case of MS from Australia, Scandinavia, the United Kingdom, and the United States.
Previous studies have implicated the MHC, but also regions on other chromosomes, as harboring genes that increase MS risk. Haines suggests that these studies failed to include enough subjects.
"This is the largest genetic linkage study on MS, and the first to be done using the latest technology, which provides very detailed coverage of the entire human genome," said Haines. "Other genes may still play an important role in MS, but finding them will require using new genomic techniques."
Multiple sclerosis is an enigmatic disease of the nervous system and results in the loss of myelin, a substance that normally insulates nerve fibers and speeds electrical conduction through the fibers. Patches of inflammation (known as 'plaques') occur throughout the brain and spinal cord resulting in the loss of myelin and sometimes the nerve fibers themselves.
Depending on which nerve fibers are hindered, patients can experience problems ranging from weakness and clumsiness to numbness, visual disturbances, and even emotional and intellectual alterations. In some patients, MS manifests itself in cycles of relapse and remission and patients may show little sign of the disease between attacks.
A high density screen for linkage in multiple sclerosis Jonathan L. Haines, Ph.D. (presenting on behalf of the International Multiple Sclerosis Genetics Consortium - IMSGC).
This abstract describes the results of what we would consider to be the definitive multiple sclerosis linkage screen. The power of the study is so great that it is virtually certain that all susceptibility loci with effects large enough to be detectable by linkage have been found. The value of a definitive reliable linkage map cannot be overemphasized. The results from this study have profound implications for the future study of the genetics of this complex disorder and enable accurate minimum requirements to be determined for future studies. This is clearly a critical development in the field.
Ten centimorgan microsatellite map have been the standard tool used for whole genome linkage screening since the mid 1990's and to date 11 screens employing this methodology have been published in multiple sclerosis. However the scale and quality of the data in these studies is limited. In order to establish a definitive linkage map we have typed 4506 single nucleotide polymorphism markers in a set of 730 multiplex families from Australia, Scandinavia, the United Kingdom and the United States, which together provide 945 affected relative pairs. Highly significant linkage is observed in the region of the Major Histocompatibility Complex (lod score 11.7) and suggestive linkage is identified on chromosome 17 and 5. Ordered Sub-set analysis identifies a further locus on chromosome 19. The mean information extraction provided by the marker panel is 79.3% (range 42.4 - 91.3%) and the observed Mendelian inconsistencies suggests that within this data set the genotyping error rate is just 0.002%. These data have profound implications for the future directions of multiple sclerosis genetics research and suggest that previous efforts in this area are almost all substantially underpowered. In the future association studies will need to include at least 500-1000 cases.
American Neurological Association
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