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KW - Common variant/common disease (CVCD) hypothesis

Not all monogenic diseases demonstrate marked allelic diversity. Several factors may explain this situation. Most simply is the case of heterozygous advantage. In this scenario, alleles whose pathologic effect is biased toward recessivity can confer a selective advantage when present as a single copy. There are several well-characterized examples of polymorphisms that exhibit some degree of protection from malaria, for example, G6PD deficiency at the G6PD locus, and HbC and HbS at the HBB locus in West African populations; the estimated allele frequencies being 0.20, 0.09, and 0.10, respectively. Selection may operate during the phase of population expansion, and it may increase the frequency of certain alleles in the population in the preexpansion phase. For example, the mutations that give rise to cystic fibrosis (CF) do not immediately appear to comply with the arguments set out above. More than 900 alleles of the CF transmembrane conductance (CFTR) gene have been associated with CF, however, approximately 70% of cases are due to one single deletion, AF508. It has been postulated that heterozygotes carrying CFTR mutations may have some selective resistance to Salmonella typhi (Pier et al., 1998). Irrespective of the mechanism, it can be shown that for an allele as frequent as AF508 in the preexpanded population this simple ancestral spectrum will persist following expansion with a half-life of 39 000 to 390 000 years, depending on the assumed mutation rate (Reich and Lander, 2001).

It is plausible that these common variants

You may find Viktor Frankl's works more accessable.It sounds corny today, but the idea that mental therapy shouldfocus on the here-and-now,doing your own thinking (including "finding meaning" and "finding an answer for death"),accepting life even when it is not perfect,changing fixed ways of thinking,and taking responsibility for your outcomeswas radical in its day (notably the 1950's).

T2 - Rare variants or "common gene, common disease"?

Since this is a subcortical process, expect rigidity, gait, and bladder problems.In spite of what anyone else may tell you,Binswanger's is common, and is one of the great "unnoticed diseases" of the late twentiethcentury (common illnesses that until recently were overlooked routinely.)

The major pseudoautosomal region (PAR1) at thetip of the short arms has very high recombination frequency (the sex-averagedrecombination frequency is 28% which, for a region of only 2.6 Mb, isapproximately 10 times the normal recombination frequency).

Thankfully the disease is becoming less common, but has not vanished.

This is coming to be much better known than in the past, and with new imaging studies,we've found that when notable white matter changes are discovered incidentallyin an older person, that person will probably have rapid, global decline in function (BMJ 339: b2477, 2009).

Inclinical settings genetic heterogeneity refers to the presence of a variety ofgenetic defects which cause the same disease, which may be the mutations atdifferent positions on the same gene, a finding common to many human diseases(including Alzheimer's disease, cystic fibrosis, lipoprotein lipase andpolycystic kidney disease).

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The cell-phone / brain tumor lawsuits are becoming an industry.

MOYAMOYA DISEASE, a poorly-understood process in which the vessels of the circle of Willis andnearby become narrowed (fibrosis of the intima) and may also bleed (fragile new vessels sprout), is yet another cause of stroke.

Common Disease, Multiple Rare (and Distant) Variants - …

We have already seen infarcts due to compression of vessels during herniation, and "border zone infarcts /watershedinfarcts" in which there is hypoperfusion but no obstruction.

common disease, common variant” hypothesis), ..

Immunization has made the disease much less common in the developed countries, and its occurrence in recent memory among anti-immunization cultists (four among the Amish MMWR 46: 1194, 1997; Netherlands "orthodox reformed churches"Lancet 344: 665, 1994 has 68 sick, two dead; Minnesota Amish get vaccine-derived reverted polioJ.

a single common variant, and the multiple rare …

Lay wisdom is that "cerebral palsy is the obstetrician's fault, the baby did not get enough oxygen to the brain." (Ask a lawyer; this is probably true only of a minority of cases; the advances in obstetrical and neonatal care in the last few decades have had no measurable impact on the rate of cerebral palsy.) What we DO know is that about 40%of cerebral palsy cases come from among the 1.5% of babies bornweighing less than 1500 gm (NEJM 358: 1700, 2008).

Common disease-common variant - Wikipedia

In "consanguinous families",it's very common and though no loci have been found yet, various subtypes have beenidentified (Neurology 76: 373, 2011).

We briefly discuss the common-disease common-variant hypothesis…

CREUTZFELDT-JAKOB DISEASE (CJ disease or JC disease; the former is preferred now because this Creutzfeldt described it first and the disease has nothing to do with JC virus) is a relatively uncommon (annual incidence 1/million in most societies), dementing disorder that usually strikes between ages 40 and 60, no sex predominance.

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