MS genetics

[Guest guest]

So I was thinking to myself: if Scandinavians live so far north surely they have well-adaptedmechanisms for coping with and adjusting to changes in the length of the day. Of all people,why would they be most prone to MS?

I thought about a scenario. Young Viking men go on a long long exploration aboard ship. Theyland. They even settle some places. Because not only do they find food and trees, there issomething else here they haven't seen since they left home: women!

Some marry and their progeny return to Scandinavia.

"Genetic Studies conducted on full-blooded indigenous populations from North, Central, andSouth America (the New World) has identified a limited number of shared genetic markers.These markers have very specific modes of inheritance and are relatively unique to populationswith Native American Ancestry. There are 2 types of inheritance pattern categories that thesemarkers follow, either a directly paternal linkage (i.e., male-to-male-to-male, etc.) or adirectly maternal linkage (i.e., female-to-all her children. Then, only the female childrenpass it on to all their children)....The data also demonstrates a possible 4th migration the actually took place about 15 thousandyears ago. Some researchers have suggested that this group could be related to the ScandinavianVikings, and may have crossed the Atlantic and mixed with Native Americans that crossed theBering Strait (haplogroup X).

The markers passed from mother to children are carried in the mitochondrial DNA (mtDNA)" [1]

This haplogroup X is the sons and daughters of the Vikings who mixed with Native Americans.

Perhaps the genes and alleles that come from America do not produce appropriate proteins tohelp the circadian clock adjust to changes in day length.

Mybe the offspring of this haplogroup X have a new disease: MS.

These folks don't do as well taking long ocean voyages.

So why do twice as many women as men get it? Does *that* have to do with their ancestry?No. It is a property of genes, the haplogroup X genes, but it's a few other thingsbesides.

"It is also the case that women's genetic make-up is different to men's, having two X-chromosomes whereas men have one X- and one Y-chromosome. Whether one or more of the hypothetical multi- factorial genes that confer an increased risk of MS or other autoimmune diseases lies on the X-chromosome is something worth considering." [2]

But that would make it a recessive trait, like red hair or baldness. I would have thoughtthat would be noticed.

"...steroids exhibit dose-dependent biphasic effects on immune cells, whereby low concentrations facilitate, and high doses inhibit, cell-mediated immune functions ."

"...a biphasic dose effect has been ascribed to estrogen, with low doses facilitating and higher doses inhibiting immune cell functions. Other sexually dimorphic hormones, such as prolactin, GH, and IGF-1 may play a role in the enhanced immune responses in females. [3]"

Don't these dosage effects sound familiar? How many more hormones, or hormone receptor agonists and antagonists, are like that (biphasic wrt dosage)?

Estrogen allele ESR1 when combined with Human Leukocyte Antigen complex allele DR2has been shown to affect MS risk (Mattila et al.), having influence on the familiar 2 to1 ratio of women MS sufferers. [3]

[1] http://www.genetree.com/product/native-american-test.asp

[2] http://www.mult-sclerosis.org/whogets.html

[3] Mattila, K.M., Luomala, M., Lehtimaki, T., Laippala, P., Koivula, T., Elovaara, I.Interaction between ESR1 and HLA-DR2 may contribute to the development of MS in womenNeurology 2001 56: 1246-1247

[4] Whitacre CC, Blankenhorn E, Brinley FJ Jr, et al. Sex differences in autoimmune disease:focus on multiple sclerosis. In: Science [online].Available at: www.sciencemag.org/feature/data/983519.shl.

[5] A Gender Gap in Autoimmunity Caroline C. Whitacre, C. Reingold, A. O'Looney, and the Task Force on Gender,Multiple Sclerosis and Autoimmunity<http://www.sciencemag.org/cgi/content/full/283/5406/1277>

[6] Effect of human leukocyte antigen heterozygosity on infectious disease outcome: Theneed for allele-specific measuresMarc Lipsitch,Carl T Bergstrom RustomBMC Medical Genetics 2003 4:2The electronic version of this article is the complete one and can be found online at:<http://www.biomedcentral.com/1471-2350/4/2>