Mycobacterial disease leprosy

Unlike tuberculosis, leprosy is not a disease with a significant mortality rate, but with sometimes devastating effects on nerves and skin, it can have severe consequences on quality of life and significant social and economic effects on a community. Leprosy consists of two forms tuber-culoid and lepromatous. Tuberculoid is characterized by strong cell-mediated immunity, a Th1 CD4+ cytokine profile (interferon-g, interleukin-12) and very few bacteria in skin lesions. Lepromatous on the other...

Summary

Interaction effects are extremely important because they cause the additive effects of alleles to change as the genetic and environmental background of a population changes. Mapping studies are often best at detecting additive effects therefore the prevalence of GEI and epistasis that is emerging from model organism research has profound implications for the success and repro-ducibility of disease mapping studies in humans. A large number of QTL identified by Dilda and Mackay (2002) were only...

References

Micronutrient deficiencies. A major cause of DNA damage. Ann N YAcad Sci, 889, 87-106. Antoniou, A.C., Pharoah, P.D., Mcmullan, G. et al. (2002). A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes. Br J Cancer, 86, 76-83. Arlett, C. F. and Lehmann, A. R. (2004). Xeroderma pigmentosum, Cockayne syndrome and trichothio-dystrophy sun sensitivity, DNA repair defects and skin cancer. In Eeles, R., Easton, D.F., Ponder, B.A.J. and Eng, C.,...

Multilocus models and linkage disequilibrium

Analysis of single locus models, as above, has yielded a great deal of insight into the dynamics of populations. However, genetic mapping methods rely fundamentally on the relationships between linked markers, both for linkage and association mapping. Therefore we must also understand the relationships between loci. The simplest multi-locus model considers the relationship between two biallelic loci on the same haplotype, or gamete. Consider two loci, 1 and 2, segregating alleles 'A' and 'a',...

Localized LD patterning

Having discussed factors that influence the shaping of LD across the genome as a whole, we shall now focus our attention on factors that influence LD on a more localized level, the two most important being recombination and selection. The average effect of recombination is to reduce linkage disequilibrium. This can be readily seen in terms of the dynamic for haplotype frequency change where recombination reduces the frequency of haplotypes that are in excess. X1' X1 - rD X 2' X 2 + rD X 3' X 3...

SNP selection

Association studies of a candidate region or other region of interest should aim unless it is a replication study to ensure that association is tested using all known variants above a specified frequency either directly or indirectly through the known association between genotyped and unge-notyped variants. After the first reporting of linkage disequilibrium in ''blocks'' across the genome Gabriel et al., 2002 a plethora of papers emerged in 2003-4 on methods to determine haplotype blocks and...