Gene inversion

The copper-containing nitrite reductase from A. cycloclastes may also have evolved from this ancestral oxidase. Nitrite reductase is a two-domain protein that functions as a trimeric molecule. During its evolution from the ancestral copper oxidase, a gene inversion must have occurred, so that domain 2 of the ancestral oxidase is now domain 1 of nitrite reductase. Domain 1 of the ancestral oxidase lost its type-1 copper but has become domain 2 in nitrite reductase after the gene inversion. 

Gene inversion—A rearrangement of the gene or part of the gene causing the orientation of the DNA sequences in the gene to be reversed in relation to the flanking chromosomal DNA sequences. 

Lozier JN, Dutra A, Pak E, Zhou N, Zheng Z, Nichols TC, et al. The Chapel Hfil hemophilia A dog colony exhibits a factor VIII gene inversion. Proc Natl Acad Sci USA 2002 99 12991-6. 

Vnencak-Jones CL, Phillips JA, Janco RL, Cohen MP, Dupont WD, Kazazian HH, et al. Analysis of factor VIII gene inversion mutations in 166 unrelated haemophilia A families frequency and utility in genetic counseling. Haemophilia 1996 2 18-23. 

Patients with severe hemophilia A should be tested for the common factor VIII gene inversions. If the patient has this mutation, family members should undergo testing to determine if they also have the mutation and thus are carriers. In those patients with hemophilia A who lack the inversion mutation, other methods to determine the carrier status of their family members are available. Techniques to determine carrier status in families with hemophilia B are similar, although no predominant mutation like the factor VIII inversion has been found. The smaller size of the factor IX gene facilitates direct DNA mutational analysis. ... 

Meyer RD, Eaz EV, Su T, Waxman DJ (2009) Male-specific hepatic Bcl6 growth hormone-induced block of transcription elongation in females and binding to target genes inversely eoordinated with STATS. Mol Endocrinol 23 1914-1926... 

As for HIV, the selection of HCV drug resistant variants can be accompanied by a decrease in RC. For HCV protease inhibitor resistant variants, the level of resistance seems to be inversely related to viral fitness (Sarrazin et al. 2007 Tong et al. 2006 Yi et al. 2006). There is some evidence that viral RC can be restored by the selection of compensatory mutations within the protease gene (Sarrazin et al. 2007 Tong et al. 2006 Yi et al. 2006). However, further research is warranted to investigate to what extent viral fitness can be restored and by which mutations. Also for the nucleoside and non-nucleoside inhibitors, the selection of resistance results in a fitness defect. It remains to be investigated whether or not compensatory mutations can be selected. 

After expression of poly(VPGXG) genes, the biopolymer can easily be purified from a cellular lysate via a simple centrifugation procedure, because of the inverse temperature transition behavior. This causes the ELPs to undergo a reversible phase transition from being soluble to insoluble upon raising the temperature above the and then back to soluble by lowering the temperature below Tt (Fig. 9). The insoluble form can be induced via addition of salt [27]. The inverse transition can... 

Epidermal nerve fiber analysis by immunocytochemical techniques using the panaxonal marker protein gene product 9.5 (PGP 9.5) allows the study of epidermal innervation by small fiber C and A5 nerve fibers (McCarthy et al. 1995 Holland et al. 1997). Studies of skin biopsies of HIV infected patients with DSP or ATN showed reduction in the number of epidermal fibers in distal areas of the lower extremities with an inverse correlation between neuropathic pain intensity and epidermal nerve fiber density (Polydefkis et al. 2002) (Fig. 4.3). There were also fewer epidermal fibers in HIV seropositive patients without clinical evidence of neuropathy, suggesting that HIV infection may be associated with the loss of cutaneous innervation even before the onset of sensory symptomatology (McCarthy et al. 1995). 

Frischer, L. E., Hagen, F. S., and Garber, R. L. (1986). An inversion that disrupts the Antennapedia gene causes abnormal structure and localization of RNAs. Cell 47 1017-1023. 

Thymidylate synthase (TS) is the rate-limiting enzyme in the DNA synthetic pathway and the target for 5-FU and folate analogs (Figure 14.3). Compared to normal tissues, TS is often overexpressed in tumor cells, probably as a result of tumor suppression loss of function, gene amplification or other mechanisms. Acute induction of TS protein as well as stable amplification of TS-specific genes may be associated with resistance to fluoropyrimidine derivatives [118, 119], and an inverse correlation between tumor TS expression and clinical response was found [120-122]. 

The genes that respond to a specific hormone contain identical HRE (Fig. 1.6). Normally, it is a matter of short nucleotide sequences pentamers or hexamers. In the case of the ER, the sequences are found repeated in inverse order in the same strand of DNA (palindromic, or symmetrically legible sequences 5 GGACA-nnn-ACAGG 3 n is any nucleotide). In the case of the thyroid hormones and retinoic acid, the HRE at times are presented like two repeated sequences in the same order (direct repetition GGACA-GGACA). 

Inversions. When two breaks occur in the same chromosome, the portion between them is detached and becomes reinserted in the opposite way to its original position, that is, the gene order is reversed. This need not cause a genetic problem, but imbalanced gametes could result in congenital malformation or fetal death. 

G8. Gavish, D., Azrolan, N., and Breslow, J. L., Plasma Lp(a) concentration is inversely correlated with the ratio of kringle IV/kringle V encoding domains in the apo(a) gene. J. Clin. Invest. 84, 2021-2027 (1989). 

It is SREBPs which coordinate the expression of HMG CoA reductase and cell surface receptors for LDL. Cholesterol is an essential component of membranes so if delivery of cholesterol to the cell is limited by low concentrations of LDL-cholesterol, the expression of the genes for both the LDL receptor and HMG CoA reductase are up-regulated allowing the cell to extract as much as possible form the circulation and also to synthesize cholesterol, thus there is an inverse relationship between plasma LDL-cholesterol concentration and HMG CoA reductase activity. 

---