Variability in genes

Abstract The existence of neuronal nicotinic acetylcholine receptor (nAChRs) expression in the brain was discovered 30 years ago. Although the relevance of neuronal nAChRs at the time of their discovery was debated, it is now clear that nAChRs are expressed throughout the brain where they mainly serve a modulatory role. Neuronal nAChRs increasingly have become of interest due to the many observations that various nAChR subtypes exhibit abnormal expression or function in a wide assortment of neurological diseases. In this review, the putative role of nAChRs in brain disease is discussed in several broad categories (1) diseases associated with a loss of nAChRs, (2) diseases associated with innate differences in the expression of nAChRs, (3) diseases associated with genetic variability in genes that code for nAChR subunit proteins, and (4) diseases in which nAChRs are implicated based on the observation that nicotine has a therapeutic effect. 

Rogue A, Lambert C, Spire C et al (2012) Interindividual variability in gene expression profiles in human hepatocytes and comparison with HepaRG cells. Drug Metab Dispos 40 151-158... 

Liposomes and lipoplexes are usually self-assembling, easy to prepare and biodegradable. They allow increased uptake of naked DNA and DNA NPs. They can also be combined with polycations to form lipid-DNA NPs. Caracciola et al. [8] observed that lipid-protamine-DNA (LPD) NPs were more efficient than lipoplexes for gene delivery in CHO (Chinese hamster ovary cells), HEK293 (human embryonic kidney cells), NIH 3T3 (mouse embryraial cells) and A17 (murine cancer cells) cells. Unfortunately, cationic liposomes exhibit significant variability in gene delivery efficiency and are often toxic to cells. 

Sanchez A, Garcia HG, Jones D, Phillips R, Kondev J (2011) Effect of promoter architecture on the cell-to-cell variability in gene expression. PLOS Comput Biol 7 el001100 Schulz A, Langowski J, Rippe K (2000) The effect of the DNA conformation on the rate of NtrC activated transcription of Escherichia coli RNA polymerase sigma(54) holoenzy me. J Mol Biol 300 709-725... 

Raj, A., Rifkin, S. A., Andersen, E., and van Oudenaarden, A. 2010. Variability in gene expression underlies incomplete penetrance. Nature 463 913-918. 

Mutation is a stable, heritable change of a gene from one allele to another, which both creates and maintains genetic variability in populations. Most mutations adversely affect the survival and reproductive success of their bearers, but if the physical or biological environment changes, previously neutral or harmful alleles may become beneficial. Mutation rates typically are very low, but they are sufficient to create considerable genetic variation over many generations. 

Nurse Even if it was one gene you could set up the system so that it would have limited variability. It would depend on the numbers of molecules involved in that circuit. You can devise limited variability in different ways. One is by having many different elements in the way that you have described, but you can also do it by having lots of molecules involved in a single regulatory circuit, which would reduce variability. 

It is important to realize, that diseases such as myocardial infarction or type 2 diabetes represent a heterogeneous group of several distinct subphenotypes definable by clinical or biochemical characteristics. Thus, contradictory findings in pharmacogenomic studies may only not be the consequence of a lack of a major isolated gene effect (of the gene variant studied) and chance findings, but also be caused by the variability in the mix of distinct clinical phenotypes hidden beneath a common characterization such as type 2 diabetes and modulated by differences in the environment between studies. 

The G/A promoter polymorphism at the apoAI gene locus predicts individual variability in fasting and postprandial responses to the HMG CoA reductase inhibitor atorvastatin. Circulation 1999 100(Suppl I) I—239. 

---