廣泛的區域內和跨民族的轉錄變化反映了人類的適應和自然選擇。基因表達是轉化基因組信息為功能基因產品 - 蛋白質的主要機制。異常基因的表達和疾病的發病機制有關。基因組革命提供了獨特的機會為複雜的人類轉錄組進行全面的研究。轉錄分析需要複雜的生物信息學方法。在技術角度，一個實證模型用了哺乳動物基因組中內含子長度幾何尾分佈的定律準確地確定剪接交界處和非唯一映射讀取的位置。這種方法在處理非唯一映射讀取比BWA更好。這方法還比其他工具檢測出更多已經實驗證實的剪接交界處。核糖核酸測序首先用於北京漢人和西歐之間的表達表型與的轉錄變化的詳盡研究。民族的具體剪接交界處被發現。此外，民族的具體特點體現在相對異構體的豐度差。最後，這分子表型剪接頻譜的變化在不同種族之間的不同表明了另一個描繪種族多樣性的方法，核糖核酸測序還被用於探索的一種複雜的疾病：二型糖尿病的分子異常。二型糖尿病表現在廣泛不同的基因表達。（1）這研究證實先前公佈的全基因組關聯研究;（2）改善策劃不佳的位點和（3）發現新型2型糖尿病相關的基因。本研究通過整合各種改變的信號，並在一個高度可信的基因 - 基因相互作用網絡進行解釋，增強表達異常在2型糖尿病的認識。在更廣泛的69×79的情況下，對照組的結果進行了驗證。本研究增強表達異常在2型糖尿病的認識。 / Extensive intra- and inter- ethnic transcriptome variation reflects human adaptation and natural selection. Gene expression is the primary mechanism that translates genome information into functional gene product that lead to physiological phenotypes. Aberrant gene expression has been associated to the pathogenesis of diseases. The genome revolution has offered unique opportunity for a comprehensive interrogation of the complexity of human transcriptome. Analysis of transcriptome using RNA-Seq requires sophisticated bioinformatics approach. In a technical perspective, an empirical model based on the geometric-tail distribution of intron lengths in mammalian genome was developed to accurately determine splice junctions from junction reads and locations of non-uniquely mapped reads. Such method handles non-uniquely mapped reads better than BWA. The method can also detect more experimentally confirmed splice junction than other tools. Expressional phenotyping was employed to explore global transcriptomic variation between Beijing Han Chinese and Western European. In addition to inter-ethnic variations in gene expression, ethnic specific splice juctions were found. Further, ethnic specific trait manifests in differential relative isoform abundance. Lastly, such spectrum of variations was different between different ethnic groups, suggesting alternative splicing as another molecular phenotype that delineates ethnic diversity. Expressional phenotyping was then used in a case-control study to explore the molecular abnormalities of a complex disease: Type 2 Diabetes (T2DM). T2DM manifested in wide-spread repression of gene expression. The study (1) confirmed previously reported Genome-wide Association Study (GWAS) loci; (2) curated poorly characteriezed GWAS loci and (3) discovered novel T2DM associated genes. By integrating various alteration signals and interpretation performed in a highly confident gene-gene interaction network, this study augmented the understanding of expressed abnormalities in T2DM. The results were validated in a broader 69 x 79 case-control group. / Detailed summary in vernacular field only. / Li, Jing Woei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 118-130). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.v / 中文擇要 --- p.vi / Thesis/Assessment Committee --- p.ix / Acknowledgement --- p.ix / List of figures --- p.x / List of tables --- p.xii / List of Abbreviations --- p.xiii / Scientific contributions --- p.xv / List of Publication(s) related to this thesis --- p.xvi / Conference presentations --- p.xvii / Chapter Chapter 1: --- Introduction and Literature Reviews --- p.1 / Chapter 1.1 --- The variable human transcriptome --- p.1 / Chapter 1.2 --- Significance of variation in gene expression and transcript variants --- p.2 / Chapter 1.3 --- Transcriptomic study in a technological perspective --- p.8 / Chapter 1.3.1 --- Microarray: Probing what was designed to be probed --- p.8 / Chapter 1.3.2 --- RNA-Seq: the ab initio decoder of biological sequences --- p.9 / Chapter 1.4 --- Analysis of RNA-Seq data --- p.10 / Chapter 1.4.1 --- The bioinformatics challenges prevail --- p.10 / Chapter 1.4.2 --- Identifying changes in gene expression --- p.16 / Chapter 1.4.3 --- Identifying splice site, quantification of isoform level expression --- p.17 / Chapter 1.5 --- Conclusion --- p.19 / Chapter 1.6 --- Aims of this study --- p.20 / Chapter 1.6.1 --- Splice junction determination --- p.20 / Chapter 1.6.2 --- Expressional phenotyping in ethnical context --- p.20 / Chapter 1.6.3 --- Expressional phenotyping in a disease context --- p.20 / Chapter Chapter 2: --- Detection of splicing events --- p.21 / Chapter 2.1 --- Abstract --- p.21 / Chapter 2.2 --- Introduction --- p.22 / Chapter 2.3 --- Methods and workflow --- p.25 / Chapter 2.4 --- Algorithm --- p.29 / Chapter 2.5 --- Geometric-tail distribution --- p.32 / Chapter 2.6 --- Insert-size distribution --- p.33 / Chapter 2.7 --- Multiread analysis --- p.34 / Chapter 2.7.1 --- GT model probably places multiread more accurately than BWA --- p.35 / Chapter 2.8 --- Splice-site comparison --- p.37 / Chapter 2.8.1 --- GT model discovers more experimentally confirmed splice junction --- p.37 / Chapter 2.8.2 --- GT model is highly accurate --- p.39 / Chapter 2.9 --- Discussion --- p.40 / Chapter 2.10 --- Limitation --- p.40 / Chapter Chapter 3: --- Transcriptomic variation in a ethnicity context --- p.41 / Chapter 3.1 --- Abstract --- p.41 / Chapter 3.2 --- Introduction --- p.42 / Chapter 3.3 --- Materials and Methods --- p.46 / Chapter 3.3.1 --- HapMap lymphoblastoid cell-lines --- p.46 / Chapter 3.3.2 --- Sequenced samples --- p.48 / Chapter 3.3.3 --- Paired-end RNA-Seq, dataset and reads processing --- p.48 / Chapter 3.3.4 --- Genome reference and annotation --- p.49 / Chapter 3.3.5 --- Strategies for reads mapping --- p.49 / Chapter 3.3.6 --- Pathway and Gene Ontology analysis --- p.50 / Chapter 3.3.7 --- Differential gene expression analysis --- p.50 / Chapter 3.3.8 --- Ethnic specific splice junction --- p.51 / Chapter 3.3.9 --- Junction sites saturation analysis --- p.51 / Chapter 3.3.10 --- Ethnical novel transcribed regions --- p.52 / Chapter 3.3.11 --- Isoform dynamics and meta-analysis --- p.53 / Chapter 3.4 --- Result --- p.54 / Chapter 3.4.1 --- Paired-end RNA-Seq --- p.54 / Chapter 3.4.2 --- Differential gene expression and meta-analysis --- p.56 / Chapter 3.4.3 --- Ethnic specific splice junction is rare --- p.58 / Chapter 3.4.4 --- Saturation of discovery of highly confident annotated junctions --- p.59 / Chapter 3.4.5 --- Novel transcribed regions --- p.62 / Chapter 3.4.6 --- Isoform dynamics and meta-analysis --- p.63 / Chapter 3.5 --- Discussion --- p.66 / Chapter 3.6 --- Limitations --- p.67 / Chapter 3.6.1 --- HapMap LCLs may not reflect the entire spectrum of natural variation --- p.67 / Chapter 3.6.2 --- Sequencing depth and the usefulness of published dataset --- p.67 / Chapter 3.6.3 --- Knowledge gap in understanding of the human genome --- p.69 / Chapter Chapter 4: --- Transcriptomic investigation of complex disease: Type 2 Diabetes --- p.70 / Chapter 4.1 --- Abstract --- p.70 / Chapter 4.2 --- Introduction --- p.72 / Chapter 4.3 --- Materials and Methods --- p.75 / Chapter 4.3.1 --- Subjects --- p.75 / Chapter 4.3.2 --- Strand-specific RNA-Seq Library Construction --- p.77 / Chapter 4.3.3 --- Genome annotation sequencing reads processing --- p.81 / Chapter 4.3.4 --- Reads mapping for expression analysis --- p.82 / Chapter 4.3.5 --- Differential Gene expression analysis --- p.82 / Chapter 4.3.6 --- GWAS candidate genes --- p.83 / Chapter 4.3.7 --- Individual network, pathway and Gene Ontology analysis --- p.83 / Chapter 4.3.8 --- Alternative Splicing Variation --- p.83 / Chapter 4.3.9 --- Reads mapping and processing for expressed genomic variants discovery --- p.84 / Chapter 4.3.10 --- Expressed and functional genomic variants --- p.85 / Chapter 4.3.11 --- Screening for gene fusion --- p.86 / Chapter 4.3.12 --- Sense and Antisense analysis --- p.86 / Chapter 4.3.13 --- Integrated multi-level T2DM alternations gene interaction network --- p.87 / Chapter 4.3.14 --- Validation of selected genes --- p.87 / Chapter 4.4 --- Results --- p.88 / Chapter 4.4.1 --- High quality strand-specific pair-ended RNA-Seq facilitated downstream analyses --- p.88 / Chapter 4.4.2 --- Definition of significance --- p.91 / Chapter 4.4.3 --- Wide-spread repressed gene expression in T2DM --- p.91 / Chapter 4.4.4 --- Confirmation and curation of T2DM GWAS loci by RNA-Seq --- p.92 / Chapter 4.4.5 --- Global expression alteration on T2DM associated genes --- p.97 / Chapter 4.4.6 --- Alteration of relative splicing isoforms variations and T2DM specific isoforms --- p.100 / Chapter 4.4.7 --- Rare and deleterious SNPs --- p.100 / Chapter 4.4.8 --- Absence of alteration in Sense/Antisense ratio and expressed fusion gene --- p.101 / Chapter 4.4.9 --- T2DM manifests a broad spectrum of expressed abnormalities --- p.101 / Chapter 4.4.10 --- Pathway-based integration of multiple levels of alteration expanded the T2DM network --- p.103 / Chapter 4.4.11 --- Validation of selected genes --- p.107 / Chapter 4.5 --- Discussion --- p.108 / Chapter Chapter 5: --- Conclusions and future perspectives --- p.115 / Chapter 5.1 --- Conclusions --- p.115 / Chapter 5.2 --- Future perspective --- p.115 / Chapter 5.2.1 --- Splicing detection --- p.115 / Chapter 5.2.2 --- Studies related to ethnicity --- p.116 / Chapter 5.2.3 --- Complex diseases --- p.116 / References --- p.118 / Appendix --- p.131

Diet recommendations to achieve target metabolic control for prevention of micro and macrovascular complications have been outlined. Although previous studies in individuals with type 2 diabetes have identified certain factors associated with adherence to diet recommendations, adherence is multi-factorial in nature and includes demographic, biological and psychosocial variables. Our main objective was to identify factors associated With dietary behaviour among individuals with type 2 diabetes attending an out-patient clinic. Furthermore, we attempted to identify factors associated with frequency of seeing the dietitian and stages of change far lower fat intake. Principal hypothesis: those who are younger, female, lower in body mass index (BMI), higher in education level, exposed to a dietitian in the past year, higher in stage of change, having greater nutrition knowledge, greater perception of risk and benefits as well as fewer perceived barriers, would consume less total and saturated fat. (Abstract shortened by UMI.)

Previous studies reported that noncompliance to diabetes treatment may result in a series of health complications. To further understand patients’ noncompliance to meal plans, a study on meal planning strategy was developed. Through a survey Certified Diabetes Educators determined which meal planning strategies were the most effective in encouraging patients’ compliance to meal plan according to age groups (18 and under, 19 to 49, 50 to 70, and 71 and above) and recency of diagnosis (newly- and non-newly diagnosed) with Type 2 diabetes. Results identified that nutrition labels had the greatest mean rating for effectiveness in age groups 18 and under, 19 to 49, and 50 to 70; and healthy food choices had the greatest mean rating for effectiveness with age group 71 and above. / Department of Family and Consumer Sciences

Thesis (M.S.)--Brigham Young University. Dept. of Physiology and Developmental Biology, 2007. / Includes bibliographical references.

Background. Type 2 diabetes is the fifth-leading cause of death in Latinos in the United States. Diabetes is a commonly occurring health condition in older adults, leading to complications that can severely impact quality of life and hasten death. The burden of diabetes is considerable in the older adult population; almost four-fifths of adults with diabetes are older than 59 years. Diabetes mortality can be reduced or delayed with effective management of the illness. Older minority adults are more likely to have higher rates of adult-onset diabetes than non-Hispanic Whites, yet few studies have examined the diabetes self-management practices of this group. These issues are particularly important to investigate in older Dominican adults in Washington Heights/Inwood, New York City, because this group has unique cultural beliefs and practices, is rapidly increasing in population, and has a variety of unmet health-related needs. This study explored specific barriers encountered (cultural and structural) and the extent to which external factors are associated with self-management practices among older Dominican community residents living in mainland US with type 2 diabetes. After 20 years of health disparities research and intervention older adults continue to have problems accessing health care due to structural and socio-cultural barriers. Methods. This investigation utilized qualitative in-depth interviews to examine the cultural and structural barriers to health care and self-management practices existing in this group. Results. Thirty Dominicans 55 years and older were recruited through a community-based senior resource center from the mainland US. Self-management practices for type 2 diabetes vary and are represented by commonly known factors, including: 1) diet modifications; 2) glucose monitoring; 3) medication adherence; 4) exercise, and 5) diabetes classes. Findings from this study illustrate that male and female participants have mixed self-management practices that assist them in managing their diabetes. In addition, participants are interested in “learning” how to manage their diabetes through their participation in classes and diabetes-related workshops. Home remedies (remedies caseros) for type 2 diabetes were identified in this study. Conclusions. Programs and services that promote healthy self-management practices of older Latino adults need to include a focus on the unique cultural beliefs and behaviors of the individual as well as the broader situational context that impacts their diabetes self-management. Such information is invaluable for researchers and health practitioners interested in diabetes self-management practices of older minority adults.

No description available.

Background. With increasing personal affluence and changes in lifestyle, there is rising prevalence of type 2 diabetes mellitus in Hong Kong. Approximately 60% of diabetic subjects in Hong Kong are asymptomatic and previously undiagnosed. Since diabetes carries significant mortality and morbidity risk, it is important to diagnose these subjects early for intervention. There are many known factors associated with development of type 2 diabetes. Some are remediable such as obesity, dyslipidaemia, hypertension, while some are non-remediable such as age and past history of gestational diabetes. Identifying high-risk subjects will increase the yield and cost-effectiveness of screening program for diabetes and related risk factors and provide useful epidemiological information on the natural history of these diseases. / Methods. I used data from several cross-sectional and prospective studies of which I was the principal investigator or one of the co-investigators to test these hypotheses. The studies include mainly the following: (1) A public utility company workforce survey on cardiovascular risk factors in 1990 (n=1513). (2) Chinese subjects with risk factors for diabetes who underwent 75 gram oral glucose tolerance test (OGTT) screening at the Prince of Wales Hospital (PWH) between 1988 and 1995 (n=3718). (3) The 'United Christian Nethersole Community Health Service' (UCNCHS) primary health screening program database in 1997 (n=17764). / Objectives & hypothesis. I aimed to study the various factors associated with the development of type 2 diabetes in Hong Kong Chinese. With this information, I can design a screening method to early identify those subjects who are at high-risk for diabetes. I hypothesize the following: (1) Many risk factors for diabetes in Caucasians are also applicable to Hong Kong Chinese. (2) The presence of multiple factors increases the risk of diabetes in a linear fashion. (3) Chinese subjects are at risk of developing diabetes at a lower threshold of obesity, which is one of the most important risk factors for type 2 diabetes. / Results. Based on a cohort of 1513 asymptomatic subjects from a workforce survey, those in the top quartile of body mass index (BMI), as compared to those in the lowest quartile, had a 4 to 10-fold increased risk of diabetes and a 2.5 to 5-fold increased risk of impaired glucose tolerance (IGT) for men and women. (Abstract shortened by UMI.) / Ko Tin Choi. / "May 2005." / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0173. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 264-283). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

published_or_final_version / Nursing Studies / Master / Master of Nursing

published_or_final_version / Medicine / Master / Master of Philosophy

Non-insulin diabetes mellitus (NIDDM) is a major health problem affecting U.S. Mexicans. A population of Southwestern Arizona, near the U.S.-Mexico border, was studied to assess the biocultural environment in which disease develops, and to determine risk factors affecting the population. This geographic area is home to a high percentage of farmworkers of Mexican origin or ancestry. A global overview of macro- and micro-level issues was used to provide the context in which the population lives, and where the disease emerges and is maintained. The discussion of historical, economic, demographic, and social issues provide the background for the understanding of the natural and the social environments. Anthropological methods and techniques were used to assess and analyze numerous factors to determine the most useful for the identification of NIDDM risk. Methods used for data gathering included anthropometric measurements, survey instruments, ethnographic interviews, life history, and participant observation. Fifty-seven households participated in the study. A total of 212 subjects were measured; a sub-sample of 79 adults was also interviewed. The study identified 17 diabetics (12 females, 5 males). Prevalence of NIDDM for the sampled population was calculated at 8.2 percent. The rate was higher among females than among males. Diabetics were older than 45 years of age, were in poor health, had more than one source of income, and depended on social safety net assistance; high parity was characteristic of diabetic females. Diabetics' blood glucose (B.G.) levels were higher than those of non-diabetics, regardless of the variables tested. Known risk factors for NIDDM were not found to be significantly strong in the determination of diabetic status nor of B.G. levels. However, the ethnographic and quantitative data suggested that physiological variables may be affected by work and occupational related risks, diluting the prediction strength of known NIDDM risk factors. The yearly cycles of farm work and the physiological demands of the tasks involved are probably the most salient risk factors in farmworkers' lives. Recommendations are provided for the incorporation of anthropological theory, methods and techniques to the study of disease processes, and for the design of public health strategies.