GENOME SCAN FOR NIDDM SUSCEPTIBILITY GENES AMONG SAMOANS
Ranjan Deka, Associate Professor
Environmental Healthuniversity Of Cincinnati
sponsored Research Services
cincinnati, Oh 45221
Grant 5R01DK055406-04 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: MGN
Abstract: Non-insulin-dependent diabetes mellitus (NIDDM) is a complex and heterogeneous disease characterized by hyperglycemia, hyperinsulinemia and peripheral insulin resistance. It is a major public health problem affecting approximately 5 percent of the world population. While substantial evidence has been presented that there is a major genetic component to NIDDM susceptibility, the identification of the major susceptibility genes for the common form of NIDDM is yet to be accomplished. Recently published studies suggest that several susceptibility loci exist, and that the occurrence and/or frequency of predisposing alleles at these loci varies among populations. In this study, we propose to conduct a genome-wide search for NIDDM susceptibility loci among the Samoans of the Western Pacific. The prevalence of NIDDM in this population is comparatively high with an incidence of approximately 20 percent. Because of their unique population history that has led to a reduction in genetic diversity and their recent exposure to modernization, it is suspected that the contribution of alleles at specific loci to NIDDM susceptibility is likely to be different in Samoans than in other populations. This objective will be achieved through three specific aims. First, 300 sib- pairs affected with NIDDM will be ascertained. Second, a genome-wide scan will be conducted using a panel of high density microsattelite polymorphisms spaced throughout the genome at a resolution of approximately 10 cM. Third, the location of NIDDM susceptibility loci will be determined by using affected-sib-pair identify-by-descent methods. The genome-wide search will overcome the shortcomings of past candidate gene approaches where positive findings have not been replicated across populations. The affected sib-pair method is the most appropriate approach for searching for NIDDM susceptibility loci, because it makes and requires no assumption about the mode of inheritance of the disease. The ultimate goal of this project is to identify specific genes that contribute to individual susceptibility to NIDDM. Areas of significant linkage identified by the 10 cM scan will be subjected to high density mapping (approximately 1.0 cM) to confirm evidence of linkage. This will be followed by a positional candidate gene analysis to identify the specific genes responsible for increased susceptibility to NIDDM
Keywords: Asian, gene expression, gene frequency, genetic mapping, genetic susceptibility, human population genetics, noninsulin dependent diabetes mellitus allele, family genetics, genetic marker, genetic polymorphism, genome, linkage mapping clinical research, computer assisted sequence analysis, genotype, glucose tolerance test, human genetic material tag, human subject, metabolism disorder diagnosis, polymerase chain reaction, radioimmunoassay, statistics /biometry
Project start date: 1998-06-15
Project end date: 2003-04-30
5R01DK055406-04 (2001): $305010
Sponsored Links Excellgen http://Excellgen.com
GENOME SCAN FOR NIDDM SUSCEPTIBILITY GENES AMONG SAMOANS
Ranjan Deka, Associate Professor
Environmental Healthuniversity Of Cincinnati
sponsored Research Services
cincinnati, Oh 45221
Grant 5R01DK055406-03 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: MGN
Abstract: Non-insulin-dependent diabetes mellitus (NIDDM) is a complex and heterogeneous disease characterized by hyperglycemia, hyperinsulinemia and peripheral insulin resistance. It is a major public health problem affecting approximately 5 percent of the world population. While substantial evidence has been presented that there is a major genetic component to NIDDM susceptibility, the identification of the major susceptibility genes for the common form of NIDDM is yet to be accomplished. Recently published studies suggest that several susceptibility loci exist, and that the occurrence and/or frequency of predisposing alleles at these loci varies among populations. In this study, we propose to conduct a genome-wide search for NIDDM susceptibility loci among the Samoans of the Western Pacific. The prevalence of NIDDM in this population is comparatively high with an incidence of approximately 20 percent. Because of their unique population history that has led to a reduction in genetic diversity and their recent exposure to modernization, it is suspected that the contribution of alleles at specific loci to NIDDM susceptibility is likely to be different in Samoans than in other populations. This objective will be achieved through three specific aims. First, 300 sib- pairs affected with NIDDM will be ascertained. Second, a genome-wide scan will be conducted using a panel of high density microsattelite polymorphisms spaced throughout the genome at a resolution of approximately 10 cM. Third, the location of NIDDM susceptibility loci will be determined by using affected-sib-pair identify-by-descent methods. The genome-wide search will overcome the shortcomings of past candidate gene approaches where positive findings have not been replicated across populations. The affected sib-pair method is the most appropriate approach for searching for NIDDM susceptibility loci, because it makes and requires no assumption about the mode of inheritance of the disease. The ultimate goal of this project is to identify specific genes that contribute to individual susceptibility to NIDDM. Areas of significant linkage identified by the 10 cM scan will be subjected to high density mapping (approximately 1.0 cM) to confirm evidence of linkage. This will be followed by a positional candidate gene analysis to identify the specific genes responsible for increased susceptibility to NIDDM
Keywords: Asian /Pacific Islander, gene expression, gene frequency, genetic mapping, genetic susceptibility, human population genetics, noninsulin dependent diabetes mellitus allele, family genetics, genetic marker, genetic polymorphism, genome, linkage mapping clinical research, computer assisted sequence analysis, genotype, glucose tolerance test, human genetic material tag, human subject, metabolism disorder diagnosis, polymerase chain reaction, radioimmunoassay, statistics /biometry
Project start date: 1998-06-15
Project end date: 2002-04-30
5R01DK055406-03 (2000): $298131
5R01DK055406-02 (1999): $348212
Grants awarded to Ranjan Deka
POPULATION GENETICS OF HUMAN HYPERVARIABLE LOCI
Ranjan Deka, Associate Professor
Environmental Healthuniversity Of Cincinnati
sponsored Research Services
cincinnati, Oh 45221
Grant 5R01GM045861-09 from National Institute Of General Medical Sciences IRG: MGN
Abstract: This is a proposal to investigate the properties of a series of 110 hypervariable loci in 11 defined human populations. The overall objective of the research is to improve our understanding of the biology of hypervariable loci. Hypervariable loci in non-transcribed, transcribed and translated regions will be compared to test the hypothesis that, because of natural selection, intrapopulation variance is reduced in coding regions. Variation in allele sizes will be compared in disease-causing trinucleotide systems versus trinucleotide systems that do not cause disease. It is hypothesized that the former will have higher mutation rates than the latter. Measures of interpopulation genetic variance will be evaluated to search for the possible effects of natural selection (in particular, balancing vs. directional or disruptive selection). Mutation rates will be measured and compared for each class of hypervariable loci (di-, tri-, and tetranucleotides), using family data. Frequency distributions of these loci will be examined to determine whether there are functional constraints on allele size
Keywords: ethnic group, gene frequency, genetic polymorphism, genome, human population genetics, nucleic acid repetitive sequence genetic marker human data, mathematical model, nucleic acid sequence, polymerase chain reaction, serology /serodiagnosis, southern blotting
Project start date: 1992-08-01
Project end date: 2001-04-30
5R01GM045861-09 (2000): $190751
5R01GM045861-08 (1999): $185372
5R01GM045861-07 (1998): $180150
5R01GM045861-02 (1993): $145372
1R01GM045861-01A2 (1992): $160904
GENOME SCAN FOR NIDDM SUSCEPTIBILITY GENES AMONG SAMOANS
Ranjan Deka, Associate Professor
Environmental Healthuniversity Of Cincinnati
sponsored Research Services
cincinnati, Oh 45221
Grant 1R01DK055406-01 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: MGN
Abstract: Non-insulin-dependent diabetes mellitus (NIDDM) is a complex and heterogeneous disease characterized by hyperglycemia, hyperinsulinemia and peripheral insulin resistance. It is a major public health problem affecting approximately 5 percent of the world population. While substantial evidence has been presented that there is a major genetic component to NIDDM susceptibility, the identification of the major susceptibility genes for the common form of NIDDM is yet to be accomplished. Recently published studies suggest that several susceptibility loci exist, and that the occurrence and/or frequency of predisposing alleles at these loci varies among populations. In this study, we propose to conduct a genome-wide search for NIDDM susceptibility loci among the Samoans of the Western Pacific. The prevalence of NIDDM in this population is comparatively high with an incidence of approximately 20 percent. Because of their unique population history that has led to a reduction in genetic diversity and their recent exposure to modernization, it is suspected that the contribution of alleles at specific loci to NIDDM susceptibility is likely to be different in Samoans than in other populations. This objective will be achieved through three specific aims. First, 300 sib- pairs affected with NIDDM will be ascertained. Second, a genome-wide scan will be conducted using a panel of high density microsattelite polymorphisms spaced throughout the genome at a resolution of approximately 10 cM. Third, the location of NIDDM susceptibility loci will be determined by using affected-sib-pair identify-by-descent methods. The genome-wide search will overcome the shortcomings of past candidate gene approaches where positive findings have not been replicated across populations. The affected sib-pair method is the most appropriate approach for searching for NIDDM susceptibility loci, because it makes and requires no assumption about the mode of inheritance of the disease. The ultimate goal of this project is to identify specific genes that contribute to individual susceptibility to NIDDM. Areas of significant linkage identified by the 10 cM scan will be subjected to high density mapping (approximately 1.0 cM) to confirm evidence of linkage. This will be followed by a positional candidate gene analysis to identify the specific genes responsible for increased susceptibility to NIDDM
Keywords: Asian /Pacific Islander, gene expression, gene frequency, genetic mapping, genetic susceptibility, human population genetics, noninsulin dependent diabetes mellitus allele, family genetics, genetic marker, genetic polymorphism, genome, linkage mapping clinical research, computer assisted sequence analysis, genotype, glucose tolerance test, human genetic material tag, human subject, metabolism disorder diagnosis, polymerase chain reaction, radioimmunoassay, statistics /biometry
Project start date: 1998-06-15
Project end date: 2002-04-30
1R01DK055406-01 (1998): $505052
GENETICS OF METABOLIC SYNDROME IN AN ISLAND POPULATION
Ranjan Deka
University Of Cincinnati, Sponsored Research Services, Cincinnati, Oh 45221
Grant 5R01DK069845-04 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Metabolic syndrome (MetS), a constellation of risk factors associated with development of cardiovascular disease and Type 2 diabetes, has reached epidemic proportions in western industrialized nations. About 47 million Americans have MetS. Consequently, it has enormous impact on public health. The hallmark of MetS is a co-occurrence of obesity, dyslipidemia, carbohydrate intolerance and high blood pressure. Familial aggregation of the individual components and the composite MetS trait suggests involvement of genetic factors. However, our knowledge concerning the genetic factors underlying MetS remains largely incomplete. We propose to undertake a thorough investigation on epidemiology and genetics of MetS in an isolated population from the island of Hvar in the eastern Adriatic coast of Croatia. The value of isolated population in complex disease gene mapping has been widely documented. The study population has a high prevalence of MetS, is ethnically relevant to the general US population, with its distinct evolutionary history of recent founding by small number of Slavic founders, geographic isolation, environmental homogeneity, extended family sizes provides a unique opportunity to understand the genetics of MetS. We propose to (1) recruit 1200 individuals above 20 years of age from five villages of Hvar, collect demographic, environmental, life-style, phenotypic, relevant clinical data, and blood samples for analysis of biochemical traits and DNA; (2) conduct appropriate analyses to estimate the effects of genetic contribution to the variability of MetS as a composite trait and its constituent phenotypes; (3) conduct a whole genome scan using a panel of densely spaced, 10K, SNP markers for linkage analysis; (4) followed by pedigree-based association studies using a ´positional candidate´ approach in the regions of significant linkage for identification of genetic variants associated with MetS. The study has enormous public health importance and its scientific merit is substantial with the potential of understanding the genetic etiology of MetS. We will study an ideal population for this research; our use of dense SNP markers for linkage and association is a state-of-the-art approach and has enormous promise for identifying loci and gene variants underlying MetS
Keywords: 20 year old; 21+ years old; Accounting; Adult; American; Architecture; Arts; Back; Biochemical; Biological; Blood Pressure; Blood Pressure, High; Blood Sample; Blood specimen; Carbohydrates; Cardiovascular Diseases; Chromosome Mapping; Classification; Clinical; Clinical Data; Collection; Complex; Croatia; D-Glucose; DNA; Data; Deoxyribonucleic Acid; Developed Countries; Developed Nations; Developing Countries; Developing Nations; Development; Dextrose; Diabetes Mellitus, Adult-Onset; Diabetes Mellitus, Ketosis-Resistant; Diabetes Mellitus, Non-Insulin-Dependent; Diabetes Mellitus, Noninsulin Dependent; Diabetes Mellitus, Slow-Onset; Diabetes Mellitus, Stable; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type II; Disease; Disorder; Dorsum; Dyslipidemias; Engineering / Architecture; Environment; Epidemic; Epidemiology; Exhibits; Extended Family; Family; Family Sizes; Family, Extended; GWAS; Gene Localization; Gene Mapping; Gene Mapping, Total Human and Non-Human; Gene variant; Genealogy; Geneologies; Genes; Genetic; Genetic Diversity; Genetic Polymorphism; Genetic Predisposition; Genetic Predisposition to Disease; Genetic Susceptibility; Genetic Variation; Genetic analyses; Genetics, Gene Mapping; Genome; Glucose; Goals; High Prevalence; History; Human, Adult; Humulin R; Hypertension; Individual; Industrialized Countries; Industrialized Nations; Inherited Predisposition; Inherited Susceptibility; Insulin; Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine-; Insulin, Regular; Investigation; Investigators; Island; Knowledge; Less-Developed Countries; Less-Developed Nations; Life Style; Lifestyle; Linkage Analysis; Linkage Mapping; Lipids; Location; MODY; Maturity-Onset Diabetes Mellitus; Measures; Metabolic syndrome; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; NIDDM; Non-Insulin Dependent Diabetes; Non-Insulin-Dependent Diabetes Mellitus; Novolin R; Nucleotides; Obesity; Pedigree; Phenotype; Polymorphism (Genetics); Polymorphism, Genetic; Population; Population Research; Population Study; Predisposition; Public Health; Recording of previous events; Records; Recruitment Activity; Research; Research Personnel; Researchers; Risk Factors; Sampling; Susceptibility; Syndrome; Systematics; T2D; T2DM; Testing; Third-World Countries; Third-World Nations; Transmission; Type 2 diabetes; Type II diabetes; Under-Developed Countries; Under-Developed Nations; Variant; Variation; Variation (Genetics); Vascular Hypertensive Disease; Vascular Hypertensive Disorder; adiposity; adult human (21+); adult onset diabetes; allelic variant; base; cardiovascular disorder; community living; corpulence; corpulency; corpulentia; density; design; designing; disease/disorder; effective intervention; family based linkage study; genetic analysis; genetic epidemiology; genetic etiology; genetic linkage analyses; genetic linkage analysis; genetic mapping; genetic mechanism of disease; genetic pedigree; genetic variant; genetic vulnerability; genome wide association scan; genome wide association studies; genome wide association study; genome-wide linkage; genome-wide scan; genomewide association scan; genomewide association studies; genomewide association study; genomewide scan; high risk; hyperpiesia; hyperpiesis; hypertensive disease; impaired glucose tolerance; indexing; ketosis resistant diabetes; linkage analyses; maturity onset diabetes; obese; obese people; obese person; obese population; pedigree structure; polymorphism; prevent; preventing; public health medicine (field); recruit; trait; transmission process; twenty year old; whole genome association studies; whole genome association study
Project start date: 2006-08-15
Project end date: 2011-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2011
5R01DK069845-04 (2009): $453350
3R01DK069845-04S1 (2009): $155626
5R01DK069845-03 (2008): $543334
5R01DK069845-02 (2007): $510187
Sponsored Links Excellgen http://Excellgen.com
1R01DK069845-01A2 (2006): $466159
POPULATION GENETICS OF HUMAN HYPERVARIABLE LOCI
Ranjan Deka, Associate Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 2R01GM045861-05 from National Institute Of General Medical Sciences IRG: MGN
Abstract: Adapted from the Investigator s ) This is a proposal to investigate the properties of a series of 110 hypervariable loci in 11 defined human populations. The overall objective of the research is to improve our understanding of the biology of hypervariable loci. Hypervariable loci in non-transcribed, transcribed and translated regions will be compared to test the hypothesis that, because of natural selection, intrapopulation variance is reduced in coding regions. Variation in allele sizes will be compared in disease-causing trinucleotide systems versus trinucleotide systems that do not cause disease. It is hypothesized that the former will have higher mutation rates than the latter. Measures of interpopulation genetic variance will be evaluated to search for the possible effects of natural selection (in particular, balancing vs. directional or disruptive selection). Mutation rates will be measured and compared for each class of hypervariable loci (di-, tri-, and tetranucleotides), using family data. Frequency distributions of these loci will be examined to determine whether there are functional constraints on allele size.
Keywords: ethnic group, gene frequency, genetic polymorphism, genome, human population genetics, nucleic acid repetitive sequence, genetic marker, human data, mathematical model, nucleic acid sequence, polymerase chain reaction, serology /serodiagnosis, southern blotting
Project start date: 1992-08-01
Project end date: 1997-11-30
2R01GM045861-05 (1997): $201397
Ranjan Deka, Associate Professor
University Of Cincinnati Sponsored Research Services Cincinnati, Oh 45221
Grant 2P30ES006096-119015 from National Institute Of Environmental Health Sciences IRG: EHS
Keywords: biomedical facility, developmental genetics, environmental health, gene environment interaction, genetic polymorphism, genetic susceptibility, human population study, family genetics, genetic mapping, human genetic material tag, human subject, patient oriented research
Project start date: 1992-06-15
Project end date: 2007-03-31
POPULATION GENETICS OF HYPERVARIABLE LOCI
Ranjan Deka, Associate Professor
Human Geneticsuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 3R01GM045861-04S1 from National Institute Of General Medical Sciences IRG: MGN
Project start date: 1992-08-01
Project end date: 1997-04-30
3R01GM045861-04S1 (1997): $4011