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.

Flood analysis of the clare river catchment considering traditional factors and climate change

The main objective of this thesis on flooding was to produce a detailed report on flooding with specific reference to the Clare River catchment. Past flooding in the Clare River catchment was assessed with specific reference to the November 2009 flood event. A Geographic Information System was used to produce a graphical representation of the spatial distribution of the November 2009 flood. Flood risk is prominent within the Clare River catchment especially in the region of Claregalway. The recent flooding events of November 2009 produced significant fluvial flooding from the Clare River. This resulted in considerable flood damage to property. There were also hidden costs such as the economic impact of the closing of the N17 until floodwater subsided. Land use and channel conditions are traditional factors that have long been recognised for their effect on flooding processes. These factors were examined in the context of the Clare River catchment to determine if they had any significant effect on flood flows. Climate change has become recognised as a factor that may produce more significant and frequent flood events in the future. Many experts feel that climate change will result in an increase in the intensity and duration of rainfall in western Ireland. This would have significant implications for the Clare River catchment, which is already vulnerable to flooding. Flood estimation techniques are a key aspect in understanding and preparing for flood events. This study uses methods based on the statistical analysis of recorded data and methods based on a design rainstorm and rainfall-runoff model to estimate flood flows. These provide a mathematical basis to evaluate the impacts of various factors on flooding and also to generate practical design floods, which can be used in the design of flood relief measures. The final element of the thesis includes the author’s recommendations on how flood risk management techniques can reduce existing flood risk in the Clare River catchment. Future implications to flood risk due to factors such as climate change and poor planning practices are also considered.