Mapping the gene for autosomal dominant restless legs syndrome in an Irish family

Restless Legs Syndrome (RLS) is a common neurological disorder affecting nearly 15% of the general population. Ironically, RLS can be described as the most common condition one has never heard of. It is usually characterised by uncomfortable, unpleasant sensations in the lower limbs inducing an uncontrollable desire to move the legs. RLS exhibits a circadian pattern with symptoms present predominantly in the evening or at night, thus leading to sleep disruption and daytime somnolence. RLS is generally classified into primary (idiopathic) and secondary (symptomatic) forms. Primary RLS includes sporadic and familial cases of which the age of onset is usually less than 45 years and progresses slowly with a female to male ratio of 2:1. Secondary forms often occur as a complication of another health condition, such as iron deficiency or thyroid dysfunction. The age of onset is usually over 45 years, with an equal male to female ratio and more rapid progression. Ekbom described the familial component of the disorder in 1945 and since then many studies have been published on the familial forms of the disorder. Molecular genetic studies have so far identified ten loci (5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p). No specific gene within these loci has been identified thus far. Association mapping has highlighted a further five areas of interest. RLS6 has been found to be associated with SNPs in the BTBD9 gene. Four other variants were found within intronic and intergenic regions of MEIS1, MAP2K5/LBXCOR1, PTPRD and NOS1. The pathophysiology of RLS is complex and remains to be fully elucidated. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterised by iron deficiency, which suggests that disturbed iron homeostasis plays a role. Dopaminergic dysfunction in subcortical systems also appears to play a central role. An ongoing study within the Department of Pathology (University College Cork) is investigating the genetic characteristics of RLS in Irish families. A three generation RLS pedigree RLS3002 consisting of 11 affected and 7 unaffected living family members was recruited. The family had been examined for four of the known loci (5q, 12q, 14p and 9p) (Abdulrahim 2008). The aim of this study was to continue examining this Irish RLS pedigree for possible linkage to the previously described loci and associated regions. Using informative microsatellite markers linkage was excluded to the loci on 5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p and also within the regions reported to be associated with RLS. This suggested the presence of a new unidentified locus. A genome-wide scan was performed using two microsatellite marker screening sets (Research Genetics Inc. Mapping set and the Applied Biosystems Linkage mapping set version 2.5). Linkage analysis was conducted under an autosomal dominant model with a penetrance of 95% and an allele frequency of 0.01. A maximum LOD score of 3.59 at θ=0.00 for marker D19S878 indicated significant linkage on chromosome 19p. Haplotype analysis defined a genetic region of 6.57 cM on chromosome 19p13.3, corresponding to 2.5 Mb. There are approximately 100 genes annotated within the critical region. Sequencing of two candidate genes, KLF16 and GAMT, selected on the assumed pathophysiology of RLS, did not identify any sequence variant. This study provides evidence of a novel RLS locus in an Irish pedigree, thus supporting the picture of RLS as a genetically heterogeneous trait.

Hearing family carers: report on research undertaken with family carers in Cork

This report details the findings of research undertaken with family carers in Cork during 2007 – 2008. The research was undertaken to elicit the views and experiences of family carers, and in so doing, to gain insight into their perspectives on family caring and on associated support mechanisms. It is hoped that, thereafter, policy can draw on these observations. Three key themes emerged from the research itself. These are (i) the role and position of the family carer in society, (ii) the process of family caring itself and (iii) access to and knowledge of key support services. This report, then, draws attention to the extent and dynamics of family caring, as seen through the opinions and experiences of carers located in and nearby Cork city. It has the following format. In the first instance we turn our attention to a discussion of family caring in Ireland, and associated supports more generally. This includes a discussion on key issues arising in the general discourse around family caring in Ireland and internationally, in order to provide a context from which to locate the experiences of carers involved in this research study. Thereafter, we detail the methodology employed in this research study, which followed a method of research enquiry that values the input of participants from the early stages of research focus and design, and which incorporates qualitative and quantitative methods of enquiry. The research was conceptualised and developed in conjunction with The Carers Association, Cork in keeping with an approach to social research that attempts to link academic and activist/advocacy interests. Its aims were to identify issues that family carers in the locality considered important, with a view to contributing to local knowledge, providing a forum for ongoing research, and to informing policy developments on carers. The focus of the report then turns to profiling carers who participated in the research, examining the care they provide, and discussing support they receive from family, friends and neighbours – from informal sources. We then look to the access carers have to formal and public, community-based support services. We examine their experiences of, and concerns with regard to some of these key services, and look at ways that such issues might be addressed. The next section concentrates on financial supports, a range of which are available to carers, for instance, to supplement income and to assist with home renovations. We look at their uptake and issues arising, again with a view to understanding and addressing them from the perspectives of the service users. Finally, the report turns its attention to aspirations that carers have for themselves; in terms of their own personal, training, and employment options. The report concludes by drawing attention to key issues discussed throughout and makes a number of key recommendations, aimed at addressing the voiced opinions and experiences of carers that have emerged through the research.

Farmers, agriculture and politics in the Irish Free State area, 1919-1936

Given the economic and social importance of agriculture in the early years of the Irish Free State, it is surprising that the development of organisations representing farmers has not received the attention it deserves from historians. While the issues of government agricultural policy and the land question have been extensively studied in the historiography, the autonomous response by farmers to agricultural policies and the detailed study of the farmers’ organisations has simply been ignored in spite of the existence of a range of relevant primary sources. Farmers’ organisations have only received cursory treatment in these studies; they have been presented as passive spectators, responding in a Pavlovian manner to outside events. The existing historiography has only studied farmers’ organisations during periods when they impinged on national politics, epecially during the War of Independence and the Economic War. Therefore chronological gaps exist which has led to much misinterpretation of farmers’ activities. This thesis will redress this imbalance by studying the formation and continuous development of farmers’ organisations within the twenty-six county area and the reaction of farmers to changing government agricultural policies, over the period 1919 to 1936. The period under review entailed many attempts by farmers to form representative organisations and encompassed differing policy regimes. The thesis will open in 1919, when the first national organisation representing farmers, the Irish Farmers’ Union, was formed. In 1922, the union established the Farmers’ Party. By the mid- 1920’s, a number of protectionist agricultural associations had been formed. While the Farmers’ Party was eventually absorbed by Cumann na nGaedheal, local associations of independent farmers occupied the resultant vacuum and contested the 1932 election. These organisations formed the nucleus of a new national organisation; the National Farmers’ and Ratepayers’ League. The agricultural crisis caused by both the Great Depression and the Economic War facilitated the expansion of the league. The league formed a political party, the Centre Party, to contest the 1933 election. While the Centre Party was absorbed by the newly-formed Fine Gael, activists from the former farmer organisations led the campaign against the payment of annuities and rates. Many of them continued this campaign after 1934, when the Fine Gael leadership opposed the violent resistance to the collection of annuities. New farmer organisations were formed to co-ordinate this campaign which continued until 1936, the closing point of the thesis.

Investigation of the function of the LNX family of E3 ubiquitin ligases in the nervous system

The Lnx1 (Ligand of Numb protein X 1) and Lnx2 genes belong to a family of PDZ domain-containing RING finger domain E3 ubiquitin ligases. mRNA expression for both genes have been reported in early murine central nervous system. However, there have been limited reports with regards to the expression patterns for both the proteins in vivo. Hence, we have attempted to characterize the significance of these proteins in the context of morphology and physiology of the central nervous system. Through our studies, we have attempted to examine closely the expression of these two genes in the murine central nervous system. We have also looked at novel interacting ligands for both proteins. Interacting partners have been examined with particular relevance to possible roles of their interactions with LNX1 and LNX2 in the functioning of the nervous system. Moreover, we have performed loss-of-function studies by way of creation and characterization of knockout mice.

The double bind for non-traditional families in post-primary settings; to tell or not to tell their family identity

This thesis involved researching normative family discourses which are mediated through educational settings. The traditional family, consisting of father, mother and children all living together in one house is no longer reflective of the home situation of many Irish students (Lunn and Fahey, 2011). My study problematizes the dominant discourses which reflect how family differences are managed and recognised in schools. A framework using Foucauldian post structural critical analysis traces family stratification through the organisation of institutional and interpersonal relations at micro level in four post-primary schools. Standardising procedures such as the suppression of intimate relations between and among teacher and student, as well as the linear ordering of intergenerational relations, such as teacher/student and adult/child are critiqued. Normalising discourses operate in practices such as notes home which presume two parents together. Teacher assumptions about heterosexual two-parent families make it difficult for students to be open about a family setup that is constructed as different to the rest of the schools'. The management of family difference and deficit through pastoral care structures suggests a school-based politics of family adjustment. These practices beg the question whether families are better off not telling the school about their family identity. My thesis will be of interest to educational research and educational policy because it highlights how changing demographics such as family compositions are mis-conceptualised in schools, as well as revealing the changing forms of family governance through regimes such as pastoral care. This analysis allows for the existence of, and a valuing for, alternative modes of family existence, so that future curricular and legal discourses can be challenged in the interest of equity and social justice.

Home, family and society: women of the Irish landed class, 1860-1914. A Munster case study

The thesis analyses the roles and experiences of female members of the Irish landed class (wives, sisters and daughters of gentry and aristocratic landlords with estates over 1,000 acres) using primary personal material generated by twelve sample families over an important period of decline for the class, and growing rights for women. Notably, it analyses the experiences of relatively unknown married and unmarried women, something previously untried in Irish historiography. It demonstrates that women’s roles were more significant than has been assumed in the existing literature, and leads to a more rounded understanding of the entire class. Four chapters focus on themes which emerge from the sources used and which deal with their roles both inside and outside the home. These chapters argue that: Married and unmarried women were more closely bound to the priorities of their class than their sex, and prioritised male-centred values of family and estate. Male and female duties on the property overlapped, as marriage relationships were more equal than the legislation of the time would suggest. London was the cultural centre for this class. Due to close familial links with Britain (60% of sample daughters married English men) their self-perception was British or English, as well as Irish. With the self-confidence of their class, these women enjoyed cultural and political activities and movements outside the home (sport, travel, fashion, art, writing, philanthropy, (anti-)suffrage, and politics). Far from being pawns in arranged marriages, women were deeply conscious of their marriage decisions and chose socially, financially and personally compatible husbands; they also looked for sexual satisfaction. Childbirth sometimes caused lasting health problems, but pregnancy did not confine wealthy women to an invalid state. In opposition to the stereotypical distant aristocratic mother, these women breastfed their children, and were involved mothers. However, motherhood was not permitted to impinge on the more pressing role of wife