Analysis of haemochromatosis mutations in the North West population

Background: Hereditary haemochromatosis is a heritable disorder caused by an inborn error in the metabolism of iron. It results in over absorption of iron by the body, which can manifest clinically as fatigue, arthritis, diabetes and cardiovascular problems. The highest prevalence for the genetic mutations that cause hereditary haemochromatosis can be found in the Irish population. Individuals with diabetes may also have haemochromatosis (and vice versa), due to the bi-directional relationship between iron metabolism and glucose metabolism. Objectives: To determine the incidence of the three haemochromatosis mutations C282Y, H63D & S65C, in a population from the North West of Ireland and to investigate whether there is an increased frequency of these three mutations in a diabetic population from the same region. Method: DNA was extracted from 500 whole blood samples (250 diabetic samples and 250 ‘control’ samples) using a Wizard™ kit. PCR was conducted utilising specific primers for each mutation and in accordance with a set protocol. Following amplification, PCR product was subjected to restriction endonuclease digestion, where different restriction enzymes (Rsa I, Nde II & Hinf I) were employed to determine the HFE genotype status of samples. Results: The incidence of C282Y homozygosity (1/83) and C282Y heterozygosity (1/6) in the ‘control’ group was similar to those reported for the general Irish population (1/83 and 1/5, respectively). Incidences of H63D homozygotes and H63D heterozygotes or ‘carriers’ in the diabetic population were greater than that of the ‘control’ population. A significant finding of this study was that of an incidence of 1/32 S65C carriers in the control population. This is, to our knowledge, the highest incidence of the genotype reported to date in the general Irish population. Statistical analysis showed that there was no significant differences between the HFE genotype frequencies in the Diabetic and Control Populations. Conclusion: Results of the study concord with published literature in terms of C282Y homozygosity and C282Y heterozygosity in the general Irish population. An increased frequency of the H63D mutation in diabetic individuals was also found but was not statistically significant. The biochemical effect of the H63D mutation is still unknown. The significance of such a high incidence of S65C carriers in the ‘control’ population warrants further investigation.

Search for very high energy Gamma radiation from the Starburst Galaxy IC 342

This thesis describes a search for very high energy (VHE) gamma-ray emission from the starburst galaxy IC 342. The analysis was based on data from the 2003 — 2004 observing season recorded using the Whipple 10-metre imaging atmospheric Cherenkov telescope located on Mount Hopkins in southern Arizona. IC 342 may be classed as a non-blazar type galaxy and to date only a few such galaxies (M 87, Cen A, M 82 and NGC 253) have been detected as VHE gamma-ray sources. Analysis of approximately 24 hours of good quality IC 342 data, consisting entirely of ON/OFF observations, was carried out using a number of methods (standard Supercuts, optimised Supercuts, scaled optimised Supercuts and the multivariate kernel analysis technique). No evidence for TeV gamma-ray emission from IC 342 was found. The significance was 0.6 a with a nominal rate of 0.04 ± 0.06 gamma rays per minute. The flux upper limit above 600 GeV (at 99.9 % confidence) was determined to be 5.5 x 10-8 m-2 s-1, corresponding to 8 % of the Crab Nebula flux in the same energy range.