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PubMed2006

PSMIX: an R package for population structure inference via maximum likelihood method.

BACKGROUND: Inference of population stratification and individual admixture from genetic markers is an integrative part of a study in diverse situations, such as association mapping and evolutionary studies. Bayesian methods have been proposed for population stratification and admixture inference using multilocus genotypes and widely used in practice. However, these Bayesian methods demand intensive computation resources and may run into convergence problem in Markov Chain Monte Carlo based posterior samplings. RESULTS: We have developed PSMIX, an R package based on maximum likelihood method using expectation-maximization algorithm, for inference of population stratification and individual admixture. CONCLUSION: Compared with software based on Bayesian methods (e.g., STRUCTURE), PSMIX has similar accuracy, but more efficient computations.PSMIX and its supplemental documents are freely available at http://bioinformatics.med.yale.edu/PSMIX.

Algorithms↗
PubMed1998

Variation in the AU(AT)-rich element within the 3'-untranslated region of PPP1R3 is associated with variation in plasma glucose in aboriginal Canadians.

We are investigating associations between variations in candidate genes on chromosome 7q and diabetes-related phenotypes in Canadian Oji-Cree. One of these genes encodes the skeletal muscle regulatory G subunit of the glycogen-associated form of protein phosphatase 1 (PPPIR3), which may play a key role in muscle glycogen metabolism. There is a common 5-bp insertion-deletion polymorphism in a messenger ribonucleic acid-stabilizing AU(AT)-rich element within the 3'-untranslated region (UTR) of PPPIR3. The D allele had a frequency of 0.30 in the Oji-Cree. We found that this 3'-UTR variation of PPPIR3 was significantly associated with variation in 2-h postprandial glucose in adult Oji-Cree with type 2 diabetes or impaired glucose tolerance (IGT). Specifically, Oji-Cree with diabetes or IGT who were D/D homozygotes had significantly lower 2-h postprandial plasma glucose than subjects with the other genotypes. There was no association of the PPPIR3 genotype either with the presence of type 2 diabetes or IGT or with other quantitative traits in this sample. These findings suggest that common PPPIR3 3'-UTR variation that potentially affects messenger ribonucleic acid stability is associated with variation in glycemia in Oji-Cree subjects with type 2 diabetes.

3' Untranslated Regions↗
PubMed1998

M. tuberculosis molecular variation in CNS infection: evidence for strain-dependent neurovirulence.

OBJECTIVE: To determine the molecular diversity among Mycobacterium tuberculosis isolates associated with central nervous system tuberculosis (CNS TB) in a defined cohort of HIV uninfected patients. DESIGN/METHODS: A retrospective analysis was performed of clinical and laboratory data for all patients with CNS TB diagnosed in Manitoba, Canada, between 1979 and 1996. Restriction fragment-length polymorphisms (RFLP) of archival isolates of M. tuberculosis from CNS TB patients were determined and interpreted against the frequency of different isolates from all TB patients in the years 1992 to 1996. RESULTS: Among 2,334 patients with active TB, CNS TB was diagnosed in 42 (1.8%); meningitis with or without tuberculoma in 76%; and tuberculoma alone in 24%. CNS TB patients were significantly more likely to be young (<40 years old), female, and of Aboriginal origin. Morbidity (fixed/recurrent CNS deficit) rate was 29% and mortality rate was 26%. An adverse outcome, either morbidity or mortality, was significantly more common in those with meningitis. RFLP analysis of isolates (n=19) from CNS TB patients revealed 13 distinct restriction patterns with a predominance of the type 1 pattern (n=6). The frequency of type 1 restriction pattern was significantly greater in patients with CNS TB compared to all TB patients in Manitoba. CONCLUSIONS: CNS TB continues to have a high morbidity and mortality despite modern methods of detection and treatment. Although several strains of M. tuberculosis cause CNS TB, the current study suggests that the occurrence of CNS TB may be strain-dependent.

Adult↗
PubMed2001

Aboriginals with multiple sclerosis: HLA types and predominance of neuromyelitis optica.

BACKGROUND: MS is common in people of northern European ethnicity who live in northern geographic areas; however, MS is rarely identified among aboriginal peoples living in the same areas. OBJECTIVES: To determine the prevalence, clinical features, HLA type, and viral infections associated with MS among aboriginals in Manitoba, Canada. METHODS: A retrospective study was performed in which the clinical features of all aboriginal patients with MS together with HLA type and human herpesvirus-6, HIV-1, human T-cell lymphotropic virus-1, and endogenous retrovirus associated with MS (MSRV) infections were analyzed and compared with results from nonaboriginal patients with MS. RESULTS: Seven aboriginals with MS were identified with a period prevalence among aboriginals of 40:100,000. Clinical features included relapsing-remitting (n = 6) or primary progressive (n = 1) phenotypes with aggressive disease courses and frequent involvement of optic nerves and spinal cord (n = 5) compared with nonaboriginal patients. Autopsy of one patient showed necrosis and eosinophil infiltrates in a cervical spinal cord lesion and a demyelinated optic nerve. Analysis of HLA alleles at the DRB1 and DQB1 loci indicated that the HLA types detected were common in aboriginals, but there were no HLA alleles previously associated with the development of MS. Analysis of the copy number of MSRV did not show differences among aboriginals and nonaboriginals with or without MS. CONCLUSIONS: Aboriginals of Algonkian background are at increased risk for an aggressive type of MS, resembling neuromyelitis optica, which is resistant to conventional MS treatments and occurs independently of HLA alleles previously associated with MS.

Adult↗
PubMed2004

The experience of urban aboriginals with health care services in Canada: implications for social work practice.

This exploratory study investigates the experience of Canadian Urban Aboriginal persons as consumers of health care services. Results highlight significant gaps in the training, skills, and knowledge of health care providers to optimally serve their Aboriginal patients. Also, several programs which are potentially most problematic for Aboriginal patients are identified. The discussion outlines important roles for hospital social workers in improving the care provided to urban Aboriginal patients.

American Indian or Alaska Native↗
PubMed2004

Breast and cervical cancer screening among Mississippi Delta women.

The purpose of the study was to determine breast and cervical cancer screening among women living in the Mississippi Delta region. Using data from the Behavioral Risk Factor Surveillance System for 1999--2000, we determined the prevalence of mammography (women 40 years and older, n = 6,028) and Pap testing (women 18 years and older, n = 6,502) within the past 2 or 3 years, respectively. We examined predictors of testing and compared results with those for women living elsewhere in the United States. Among Delta women, 69.4% (95% confidence interval [CI] 67.9% to 70.9%) had a mammogram and 85.5% (95% CI 84.3% to 86.6%) a Pap test. Mammography prevalence was lower among black and white Delta women than among black and white women elsewhere. Pap testingwas lower among older (65 years and older) Delta women or women who did not visit a doctor within the past year than among their counterparts elsewhere. Additional interventions are needed to meet the goals of Healthy People 2010 for all women.

Adolescent↗
PubMed2005

Characterization of the D18S535 STR locus in northern Ontario European and Aboriginal populations for forensic purposes.

Genetic characterization of one European and three aboriginal populations from northern Ontario was undertaken to assess the utility of the D18S535 short tandem repeat locus (STR) as a genetic marker for forensic DNA typing in the region. The D18S535 locus was amplified using monoplex polymerase chain reaction (PCR), separated by denaturing polyacrylamide gel electrophoresis (PAGE), and visualized using the silver-stain detection method. The generated population data demonstrated that the D18S535 locus is highly polymorphic with a heterozygosity of > or = 0.75. The exact test showed violations of Hardy-Weinberg equilibrium in two of the aboriginal populations. Pairwise comparisons of allele-frequency distributions indicated that the four northern Ontario populations were significantly different from each other. This test also revealed that the northern Ontario populations differed significantly from ten European populations (from Germany, Spain, and Croatia) and one population from South America (from Argentina). Forensic parameters showed that the D18S535 locus is highly discriminating (power of discrimination > or = 0.85, chance of exclusion > or = 0.51); however, the lack of Hardy-Weinberg equilibrium in some of the populations must be taken into account in the application of these results to northern Ontario forensic casework.

American Indian or Alaska Native↗
PubMed1997

Differences in sexual risk-taking behavior with state of inebriation in an aboriginal population in Ontario, Canada.

OBJECTIVE: This article describes the self-reported use of substances, participation in unprotected intercourse and differences in sexual risk-taking behavior with state of inebriation among a group of aboriginal (First Nations) people in Ontario. And, in so doing, attempts to answer some of the questions about the association between the use of alcohol and sexual risk taking in this population. METHOD: The project was developed in a partnership between an aboriginal steering committee and university researchers. Data were collected via interview from 658 randomly selected status First Nations people living within 11 reserve communities in the province. RESULTS: Of the 426 individuals included in the within subject analysis 9.6% reported variation in their participation in sex, 13.8% variation in their participation in intercourse and 10.3% variation in their participation in unprotected intercourse with inebriation. An examination of individual behavior across "sober" and "drunk or high" states showed that there were almost equal proportions of respondents who only participated in unsafe sex when sober and respondents who only participated in unsafe sex when drunk or high. Where significant differences occurred, individuals were more likely to report a shift towards no sex or no intercourse with inebriation, not towards unprotected intercourse. CONCLUSIONS: Since a large proportion of individuals in this study engage in unprotected intercourse, the small proportion of individuals reporting different sexual behavior were more likely to report participation in a safe activity rather than an unsafe activity while "drunk or high." Stereotypes and assumptions may lead educators and researchers to feel the need to focus their messages on the relationship between drug and alcohol consumption and unsafe sex; however, the amount of unsafe sexual intercourse that occurs only while individuals are inebriated suggests that this focus is not of principal concern.

Adolescent↗
PubMed2003

Markers of access to and quality of primary care for aboriginal people in Ontario, Canada.

OBJECTIVES: We evaluated primary care accessibility and quality for Ontario's aboriginal population. METHODS: We compared a defined aboriginal cohort with nonaboriginal populations with analogous geographic isolation and low socioeconomic status. We determined rates of hospitalization for the following indicators of adequacy of primary care: ambulatory care-sensitive (ACS) conditions and utilization of referral care-sensitive (RCS) procedures from administrative databases. RESULTS: ACS hospitalization rates, relative to the general population, were 2.54, 1.50, and 1.14 for the aboriginal population, the geographic control populations, and the socioeconomic control populations, respectively. The relative RCS procedure utilization rates were 0.64, 0.91, and 1.00, respectively. CONCLUSIONS: The increased ACS hospitalization rate and reduced RCS procedure utilization rate suggest that northern Ontario's aboriginal residents have insufficient or ineffective primary care.

Acute Disease↗
PubMed1998

Absence of association between genetic variation of the beta 3-adrenergic receptor and metabolic phenotypes in Oji-Cree.

OBJECTIVE: To assess the association between the common missense variant, Y64R, in the gene encoding the beta 3-adrenergic receptor, ADRB3, and intermediate phenotypes related to obesity and NIDDM in Canadian Oji-Cree. RESEARCH DESIGN AND METHODS: We determined genotypes of the ADRB3 Y64R polymorphism in 508 clinically and biochemically well-characterized adult Oji-Cree, of whom 115 had NIDDM. We tested for associations with multivariate analysis of variance. RESULTS: We found the ADRB3 R64 allele frequency to be 0.40 in this population, which is the highest yet observed in a human population. Furthermore, 15% of subjects were R64/R64 homozygotes, compared with a virtual absence of homozygotes in European study samples. However, we found no statistically significant associations of the ADRB3 Y64R genotype either with the presence of NIDDM, with indexes of obesity, or with intermediate quantitative biochemical traits related to NIDDM. CONCLUSIONS: Despite the very high frequency of the ADRB3 R64 allele in this sample of aboriginal people, it was not associated with any metabolic phenotype. This suggests that the ADRB3 R64 allele is probably not a major determinant of obesity or NIDDM in these aboriginal Canadians.

Adipose Tissue↗
PubMed2002

The prevalence of the HNF-1alpha G319S mutation in Canadian aboriginal youth with type 2 diabetes.

OBJECTIVE: To investigate the prevalence of the unique HNF-1alpha G319S mutation in a population of aboriginal youth with type 2 diabetes and to describe the relationship between clinical and historical characteristics and the presence or absence of the HNF-1alpha G319S mutation. RESEARCH DESIGN AND METHODS: Participating youth were genotyped for the G319S mutation of the HNF-1alpha gene. Clinical, laboratory, and historical data were collected via chart review (blinded to genotype results). Comparison data were derived from another study involving young nondiabetic pregnant aboriginal women. RESULTS: A total of 51 youth seen sequentially in a type 2 diabetes clinic participated in this study. Of these, 21 (41.2%) had at least one copy of the mutant allele. The allele frequency in the study population was 0.29 (95% CI 0.20-0.38), which was significantly different from the allele frequency of 0.13 in the comparison population (chi(2) = 6.78, P = 0.009). The frequency of the homozygous mutation (S319/S319) was 0.18. Mean BMI was significantly lower (P = 0.002), mean HbA(1c) was significantly higher (P = 0.02), and acanthosis nigricans was significantly less frequent (P = 0.004) in those with the mutation compared with the wild type. Mean insulin levels were lower and insulin sensitivity (assessed by homeostasis model assessment [HOMA]) was greater in the homozygote group compared with the wild-type group (P = 0.002 and P = 0.0007, respectively). A dose-dependent gradient was observed for these characteristics. CONCLUSIONS: These data support the association between the HNF-1alpha G319S mutation and early-onset type 2 diabetes in this population. Those with the mutation lacked clinical characteristics of insulin resistance (e.g., obesity and acanthosis nigricans) and had lower insulin levels, suggesting that an insulin-secretory and/or -production defect plays an important role in the development of diabetes in this group. Further investigation of the pathophysiology of the S319 homo- and heterozygote is needed because it may impact treatment and/or prevention of this disease.

Adolescent↗
PubMed2002

A comparison of rates, risk factors, and outcomes of gestational diabetes between aboriginal and non-aboriginal women in the Saskatoon health district.

OBJECTIVE: To determine possible differences in gestational diabetes mellitus (GDM) between aboriginal and non-aboriginal people in the Saskatoon Health District. RESEARCH DESIGN AND METHODS: This was a prospective survey of all women admitted for childbirth to the Saskatoon Royal University Hospital between January and July 1998. We compared prevalence rates, risk factors, and outcomes of GDM between aboriginal and non-aboriginal women. RESULTS: Information was obtained from 2,006 women, of whom 252 aboriginal and 1,360 non-aboriginal subjects had been tested for GDM. The overall rates of GDM were 3.5% for women in the general population and 11.5% for aboriginal women. For those living within the Saskatoon Health District, GDM rates were 3.7 and 6.4%, respectively. Multivariate analysis demonstrated that aboriginal ethnicity, most notably when combined with obesity, was an independent predictor for GDM. Pregravid BMI > or = 27 kg/m(2) and maternal age > or = 33 years were the most important risk factors for GDM in aboriginal women, whereas previous GDM, family history of diabetes, and maternal age > or = 38 years were the strongest predictors for GDM in non-aboriginal women. CONCLUSIONS: There may be fundamental differences in GDM between aboriginal and non-aboriginal people. Because GDM contributes to an increased risk for type 2 diabetes in aboriginal women and their offspring, the impact of prevention and optimal treatment of GDM on the type 2 diabetes epidemic in susceptible populations are important areas for further investigation.

Adult↗