27 results on '"Morgan, K."'
Search Results
2. Interleukin 10 ( IL-10) gene variants and susceptibility for paediatric onset Crohn’s disease.
- Author
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AMRE, D. K., MACK, D. R., MORGAN, K., ISRAEL, D., LAMBRETTE, P., COSTEA, I., KRUPOVES, A., FEGURY, H., DONG, J., GRIMARD, G., DESLANDRES, C., LEVY, E., and SEIDMAN, E. G.
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INTERLEUKIN-10 ,ULCERATIVE colitis ,CROHN'S disease ,GASTROENTEROLOGY ,GENETIC polymorphisms ,PEDIATRIC clinics ,PATIENTS - Abstract
Background A recent genome-wide association study in adult patients with ulcerative colitis (UC) has implicated the interleukin 10 ( IL-10) gene as an important candidate gene. Moreover, a UC-associated single nucleotide polymorphism (SNP) rs3024405 was also significantly associated with adult Crohn’s disease (CD). Aims To examine whether IL-10-CD associations extended to paediatric-onset CD. Methods We implemented the case-control design at three paediatric gastroenterology clinics in Canada. CD patients (≤20 years) were recruited along with healthy controls. DNA samples were genotyped for tag-single nucleotide polymorphisms (tag-SNPs) in the IL-10 gene. Allelic, genotype and haplotype associations with CD were studied. Results A total of 270 patients and 336 controls were studied. The mean age (±s.d.) at diagnosis was 12.1 (±3.5). There were a slightly higher proportion of male patients (56.3%). Of the five IL-10 tag-SNPs, rs2222202 (C/T) ( P = 0.03) and rs1800871 (C/T) ( P = 0.05) showed significant allelic associations with CD. Specific IL-10 SNPs were associated with CD disease location and/or disease behaviour. Conclusions Our gene-wide analysis replicates recent findings of associations between IL-10 and adult CD, and suggests that these associations extend to paediatric-onset CD as well. [ABSTRACT FROM AUTHOR]
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- 2009
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3. Breeding bird communities in a hardwood forest succession in Nova Scotia
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Freedman, B. and Morgan, K.
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FORESTS & forestry ,SPECIES diversity ,BIRDS ,ORNITHOLOGY - Published
- 1986
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4. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.
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Brown SJ, Asai Y, Cordell HJ, Campbell LE, Zhao Y, Liao H, Northstone K, Henderson J, Alizadehfar R, Ben-Shoshan M, Morgan K, Roberts G, Masthoff LJ, Pasmans SG, van den Akker PC, Wijmenga C, Hourihane JO, Palmer CN, Lack G, Clarke A, Hull PR, Irvine AD, and McLean WH
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- Canada, Case-Control Studies, Europe, Filaggrin Proteins, Genetic Association Studies, Genetic Variation, Humans, Hypersensitivity, Immediate, Ireland, Netherlands, Risk Factors, Genetic Predisposition to Disease, Intermediate Filament Proteins genetics, Peanut Hypersensitivity genetics
- Abstract
Background: IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy., Objective: To investigate the association between filaggrin loss-of-function mutations and peanut allergy., Methods: Case-control study of 71 English, Dutch, and Irish oral food challenge-positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥ 8 mm and/or peanut-specific IgE ≥ 15 kUL(-1)) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis., Results: Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge-positive patients (P = 3.0 × 10(-6); odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10(-5); odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis., Conclusion: Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)
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- 2011
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5. Genes involved in the metabolism of poly-unsaturated fatty-acids (PUFA) and risk for Crohn's disease in children & young adults.
- Author
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Costea I, Mack DR, Israel D, Morgan K, Krupoves A, Seidman E, Deslandres C, Lambrette P, Grimard G, Levy E, and Amre DK
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- Adolescent, Adult, Canada, Case-Control Studies, Child, Child, Preschool, Female, Genetic Variation, Haplotypes, Humans, Inflammation, Leukotriene B4 metabolism, Male, Polymorphism, Single Nucleotide, Crohn Disease genetics, Crohn Disease metabolism, Fatty Acids, Unsaturated metabolism
- Abstract
Background and Objectives: Epidemiological evidence for the role of polyunsaturated fatty-acids (PUFA) in Crohn's disease (CD) is unclear, although the key metabolite leucotriene B4 (LTB(4)) is closely linked to the inflammatory process. We hypothesized that inherited variation in key PUFA metabolic enzymes may modify susceptibility for CD., Methods and Principal Results: A case-control design was implemented at three pediatric gastroenterology clinics in Canada. Children ≤20 yrs diagnosed with CD and controls were recruited. 19 single nucleotide polymorphisms (SNPs) across the ALOX5 (4) CYP4F3 (5) and CYP4F2 (10) genes, were genotyped. Associations between SNPs/haplotypes and CD were examined. A total of 431 cases and 507 controls were studied. The mean (±SD) age of the cases was 12.4 (±3.3) years. Most cases were male (56.4%), had ileo-colonic disease (L3±L4, 52.7%) and inflammatory behavior (B1±p, 87%) at diagnosis. One genotyped CYP4F3 SNP (rs2683037) not in Hardy-Weinberg Equilibrium was excluded. No associations with the remaining 4 CYP4F3 SNPs with CD were evident. However haplotype analysis revealed associations with a two-marker haplotype (TG) (rs3794987 & rs1290617) (p = 0.02; permuted p = 0.08). CYP4F2 SNPs, rs3093158 (OR (recessive) = 0.56, 95% CI = 0.35-0.89; p = 0.01), rs2074902 (OR (trend) = 1.26, 95% CI = 1.00-1.60; p = 0.05), and rs2108622 (OR (recessive) = 1.6, 95% CI = 1.00-2.57; p = 0.05) were significantly associated whereas rs1272 (OR (recessive) = 0.58, 95% CI = 0.30-1.13; p = 0.10) showed suggestions for associations with CD. A haplotype comprising these 4 SNPs was significantly associated (p = 0.007, permuted p = 0.02) with CD. Associations with SNP rs3780901 in the ALOX5 gene were borderline non-significant (OR (dominant) = 1.29, 95% CI = 0.99-1.67; p = 0.056). A haplotype comprising the 4 ALOX5 SNPs (TCAA, p = 0.036) was associated with CD, but did not withstand corrections for multiple comparisons (permuted p = 0.14)., Conclusions: Inherited variation in enzymes involved in the synthesis/metabolism of LTB(4) may be associated with CD. These findings implicate PUFA metabolism as a important pathway in the CD pathogenesis.
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- 2010
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6. Association between genome-wide association studies reported SNPs and pediatric-onset Crohn's disease in Canadian children.
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Amre DK, Mack DR, Morgan K, Israel D, Deslandres C, Seidman EG, Lambrette P, Costea I, Krupoves A, Fegury H, Dong J, Xhu Z, Grimard G, and Levy E
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- Adult, Alleles, Canada, Child, Crohn Disease diagnosis, Genome, Genome-Wide Association Study, Genotype, Humans, Male, Research, Crohn Disease genetics, Polymorphism, Single Nucleotide
- Abstract
A recent pediatric-focused genome-wide association study has implicated three novel susceptibility loci for Crohn' disease (CD).We aimed to investigate whether the three recently reported and other previously reported genes/loci were also associated with CD in Canadian children. A case-control design was implemented at three pediatric gastroenterology clinics in Canada. Children <19 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in 19 reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. A total of 563 cases and 553 controls were studied. The mean (+/-SD) age of the cases was 12.3 (+/-3.2) years. Most cases were male (56.0%), had ileo-colonic disease (L3 +/- L4, 48.8%) and inflammatory behavior (B1 +/- p, 87.9%) at diagnosis. Allelic association analysis (two-tailed) showed that 8 of the 19 targeted SNPs were significantly associated with overall susceptibility for CD. Associations with one additional SNP was borderline non-significant. Significantly associated SNPs included SNPs rs1250550 (p = 0.026) and rs8049439 (p = 0.04), recently reported to be specifically associated with pediatric-onset CD.Based on the results, we confirmed associations between two of the three novel pediatric-CD loci and other regions reported for associations with either pediatric and/or adult-onset CD.
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- 2010
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7. Susceptibility loci reported in genome-wide association studies are associated with Crohn's disease in Canadian children.
- Author
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Amre DK, Mack DR, Morgan K, Israel D, Deslandres C, Seidman EG, Lambrette P, Costea I, Krupoves A, Fegury H, Dong J, Grimard G, and Levy E
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- Adolescent, Age of Onset, Canada epidemiology, Case-Control Studies, Child, Child, Preschool, Crohn Disease epidemiology, Female, Genome, Genome-Wide Association Study, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Risk Factors, Crohn Disease genetics, Genetic Loci genetics, Genetic Predisposition to Disease epidemiology
- Abstract
Background: Recent genome-wide association studies based on adult and paediatric populations have implicated >30 genes/loci as susceptibility loci for Crohn's disease (CD)., Aims: To investigate whether reported genes/loci were also associated with CD in Canadian children., Design and Methods: A case-control design was implemented at three paediatric gastroenterology clinics in Canada. Children < or =18 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in five genome-wide association studies reported genes/loci were genotyped. Associations between individual SNPs and CD were examined., Results: A total of 406 cases and 415 controls were studied. The mean (+/-s.d.) age of the cases was 12.3 (+/-3.2) years. Most cases were male (56.6%), had ileo-colonic disease (L3 +/- L4, 52.0%) and inflammatory behaviour (B1 +/- p, 86.9%) at diagnosis. Allelic association analysis (two-tailed) showed that three of the five targeted SNPs were significantly associated with overall susceptibility for CD (ZNF365, r10995271, P = 0.001; PTPN2, rs1893217, P = 0.005; STAT3, rs744166, P = 0.01). Associations with SNP rs4613763 in the PTGER4 locus were marginally nonsignificant (P = 0.07). The ZNF365 and STAT3 SNPs were predominantly associated with ileal disease with or without colonic involvement., Conclusion: The identified susceptibility genes/loci for adult-onset CD also confer risk for paediatric-onset CD.
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- 2010
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8. Investigation of reported associations between the 20q13 and 21q22 loci and pediatric-onset Crohn's disease in Canadian children.
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Amre DK, Mack DR, Morgan K, Fujiwara M, Israel D, Deslandres C, Seidman EG, Lambrette P, Costea I, Krupoves A, Fegury H, Dong J, Grimard G, and Levy E
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- Adolescent, Age Distribution, Age of Onset, Canada epidemiology, Case-Control Studies, Child, Child, Preschool, Chromosome Mapping, Cohort Studies, Confidence Intervals, Crohn Disease diagnosis, Female, Gene Expression Regulation, Genome, Human, Genome-Wide Association Study, Haplotypes genetics, Humans, Incidence, Male, Polymorphism, Single Nucleotide, Reference Values, Risk Assessment, Sex Distribution, Chromosomes, Human, Pair 20 genetics, Chromosomes, Human, Pair 21 genetics, Crohn Disease epidemiology, Crohn Disease genetics, Genetic Predisposition to Disease epidemiology
- Abstract
Objectives: A recent pediatric-focused genome-wide association study has reported novel associations of the 20q13 and 21q22 loci with inflammatory bowel disease (IBD). We aimed to investigate these associations with Crohn's disease (CD) in Canadian children., Methods: A combined case-control and case-parent design was implemented at three pediatric gastroenterology clinics in Canada. Children less than 20 years of age with a confirmed diagnosis of CD were recruited along with controls. For a subset of the patients, biological parents were also recruited. Three single-nucleotide polymorphisms (SNPs) at the 20q13 locus and 1 SNP at the 21q22 locus were genotyped. Associations between individual SNPs and haplotypes were examined., Results: A total of 410 cases, 415 controls, and 302 parents were studied. The mean (+/-s.d.) age for the cases was 12.3 (+/-3.2) years. Most cases were men (56.1%) who had ileocolonic disease (L3+/-L4, 52.2%) and inflammatory behavior (B1+/-B4, 87.0%) at diagnosis. Single SNP analysis showed that all 3 SNPs at the 20q13 locus were significantly associated with CD (rs2297441, P=2.24x10(-4); rs2315008, P=4.77x10(-4); rs4809330, P=6.08x10(-3)). Haplotype analysis suggested that the association signal at 20q13 resided on a common haplotype comprising the minor allele of rs2297441 (P=2.8x10(-5)). SNP rs2836878 at the 21q22 locus showed a trend for association with CD that was statistically not significant (P=0.06)., Conclusions: Our results support an association between the 20q13 locus and CD in Canadian children. Positional cloning studies are required to further dissect the potential causative genes in the region.
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- 2009
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9. Dietary patterns and risk for Crohn's disease in children.
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D'Souza S, Levy E, Mack D, Israel D, Lambrette P, Ghadirian P, Deslandres C, Morgan K, Seidman EG, and Amre DK
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- Adolescent, Adult, Age Distribution, Canada epidemiology, Child, Confidence Intervals, Female, Follow-Up Studies, Humans, Incidence, Male, Odds Ratio, Retrospective Studies, Risk Factors, Sex Distribution, Time Factors, Crohn Disease epidemiology, Crohn Disease etiology, Diet
- Abstract
Background: Some dietary foods are considered protective (vegetables and fruits), whereas others (fatty foods) are thought to enhance the risk for Crohn's disease (CD). The evidence, however, is inconsistent., Methods: We postulated that specific dietary patterns may influence the risk for CD. A case-control study was carried out. Newly diagnosed CD cases with population and/or hospital-based controls < or =20 years were selected from 3 tertiary hospitals across Canada. Pre-disease diet was assessed using a validated food frequency questionnaire (FFQ) administered within 1 month of diagnosis. Factor analyses and unconditional logistic regression (adjusted) was used to determine gender-specific dietary patterns and assess associated risks for CD. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were estimated., Results: A total of 149 cases and 251 controls were included. The mean age (range) of the cases was 13.3 (2.6-20 years). There were more boys (61.1%). Four dietary patterns each were observed among both boys and girls. Pattern 1 in girls, characterized by meats, fatty foods, and desserts, was positively associated with CD (OR 4.7, 95% CI 1.6-14.2). Pattern 2, common to both boys and girls, was characterized by vegetables, fruits, olive oil, fish, grains, and nuts and was inversely associated with CD in both genders (girls: OR 0.3, 95% CI 0.1-0.9; boys: OR 0.2, 95% CI 0.1-0.5)., Conclusions: Our results suggest that specific dietary patterns could be associated with higher or lower risks for CD in children. Larger prospective studies are required to confirm these findings.
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- 2008
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10. Association between genetic variants in the IL-23R gene and early-onset Crohn's disease: results from a case-control and family-based study among Canadian children.
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Amre DK, Mack D, Israel D, Morgan K, Lambrette P, Law L, Grimard G, Deslandres C, Krupoves A, Bucionis V, Costea I, Bissonauth V, Feguery H, D'Souza S, Levy E, and Seidman EG
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- Adolescent, Adult, Age of Onset, Canada, Case-Control Studies, Child, Child, Preschool, Humans, Nod2 Signaling Adaptor Protein genetics, Crohn Disease genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Receptors, Interleukin genetics
- Abstract
Background and Objectives: Interleukin (IL)-23 is a key regulator of inflammation and influences the activities of T-helper 17 (Th-17) lymphocytes. Recent reports indicate that variants in the gene coding for its receptor (IL-23R) are strongly associated with Crohn's disease (CD). We investigated whether DNA variants in the IL-23R gene determine susceptibility for CD in Canadian children., Design and Methods: A case-control and case-parent trio design was implemented at three pediatric centers across Canada. Cases of CD (=20 yr) along with their parents and controls were recruited. DNA samples were collected and genotyped for 10 single nucleotide polymorphisms (SNPs) in the IL-23R gene and three common SNPs in the CARD15 gene. Transmission disequilibrium-based tests were applied to the case-parent data and logistic regression models to the case-control data to study the association between the SNPs and CD., Results: A total of 259 CD cases, 139 controls, and 232 families (167 trios and 65 dyads) were studied. The mean age at diagnosis was 13.3 yr (range 2.6-20 yr). The majority of the patients were Caucasian. Case-control analysis revealed significant associations with three SNPs (rs1004819, rs7517847, and rs11209026 [R381Q]) and borderline nonsignificant associations with three other SNPs (rs10489629, rs10889697, and rs11465804) in the IL-23R gene. Having any CARD15 variant was associated with a significant risk for CD (P < 0.0001). Analyses of case-parent data confirmed the findings from the case-control analysis including significant associations with the R381Q SNP (P= 0.002). The common variant in this SNP conferred risk for CD. These associations were largely independent of the CARD15 gene., Conclusions: Our findings confirm recently reported genome-wide associations between the IL-23R gene and CD. They suggest that the gene is also associated with pediatric-onset CD among Canadian children.
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- 2008
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11. Autosomal recessive cerebellar hypoplasia in the Hutterite population.
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Glass HC, Boycott KM, Adams C, Barlow K, Scott JN, Chudley AE, Fujiwara TM, Morgan K, Wirrell E, and McLeod DR
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- Adolescent, Adult, Canada, Cerebellar Ataxia etiology, Cerebellar Ataxia genetics, Cerebellar Ataxia pathology, Child, Child Development Disorders, Pervasive etiology, Child Development Disorders, Pervasive genetics, Child Development Disorders, Pervasive pathology, Child, Preschool, Female, Germany ethnology, Humans, Inheritance Patterns, Intellectual Disability genetics, Intellectual Disability pathology, Male, Retrospective Studies, Syndrome, Cerebellar Diseases genetics, Cerebellar Diseases pathology, Intellectual Disability etiology
- Abstract
Cerebellar hypoplasia is a rare malformation caused by a variety of etiologies. It usually manifests clinically as non-progressive cerebellar ataxia with or without mental retardation. We further characterize a syndrome of autosomal recessive cerebellar hypoplasia in the Hutterite population, referred to as dysequilibrium syndrome (DES). We reviewed 12 patients (eight females, four males; age range 4 to 33 y) with this syndrome. Patients were examined and underwent a standard set of investigations to characterize better the clinical features, natural history, and neuroimaging of this syndrome. DES is an autosomal recessive disorder with distinct clinical features including global developmental delay, late ambulation (after age 6 y), truncal ataxia, and a static clinical course. Neuroimaging is characterized by hypoplasia of the inferior portion of the cerebellar hemispheres and vermis, and mild simplification of cortical gyri.
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- 2005
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12. Segregation of urine calcium excretion in families ascertained for nephrolithiasis: evidence for a major gene.
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Loredo-Osti JC, Roslin NM, Tessier J, Fujiwara TM, Morgan K, and Bonnardeaux A
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- Adult, Canada, Family Health, Female, Humans, Male, Middle Aged, Calcium urine, Genetic Variation, Kidney Calculi genetics, Kidney Calculi urine, Models, Genetic
- Abstract
Background: The quantitative genetics of urine calcium excretion has not been established. It is a trait of interest because hypercalciuria is commonly found in subjects with nephrolithiasis. The aim of this study was to model the segregation of this trait in a sample of French-Canadian families ascertained through a stone former., Methods: Major gene, polygenic, and mixed models were fit to 24-hour urine calcium excretion from 567 individuals in 221 nuclear families, while simultaneously taking into account gender, age at examination, body mass index (BMI), and the use of thiazide drugs. The nuclear families were extracted from 154 pedigrees, some of which were four generations, with at least two siblings with a history of calcium stones., Results: All the proposed genetic models fit the data significantly better than the null model. The most parsimonious model was the mixed codominant/polygenic model but it was statistically indistinguishable from the single-gene codominant model. In both of these models the heritability attributable to the major gene was estimated to be 0.58., Conclusion: Our results suggest that a major gene with a relatively large effect on variation in urine calcium excretion is segregating in French-Canadian families with stone formers. This implies that the power of quantitative trait segregation analysis of urine calcium excretion may be increased in these families, and results indicate that it should be feasible to genetically map the quantitative trait locus.
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- 2005
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13. Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large aboriginal Canadian family.
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Greenwood CM, Fujiwara TM, Boothroyd LJ, Miller MA, Frappier D, Fanning EA, Schurr E, and Morgan K
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- Alleles, Canada epidemiology, Chromosome Segregation, Chromosomes, Human, Pair 6 genetics, Contig Mapping, Female, Gene Frequency genetics, Genes, Dominant genetics, Genotype, HLA Antigens genetics, Haplotypes genetics, Humans, Lod Score, Male, Models, Genetic, Molecular Sequence Data, Pedigree, Penetrance, Prevalence, Tuberculosis epidemiology, Tumor Necrosis Factor-alpha genetics, Carrier Proteins genetics, Cation Transport Proteins, Chromosomes, Human, Pair 2 genetics, Genetic Predisposition to Disease genetics, Indians, North American genetics, Membrane Proteins genetics, Tuberculosis genetics
- Abstract
An epidemic of tuberculosis occurred in a community of Aboriginal Canadians during the period 1987-89. Genetic and epidemiologic data were collected on an extended family from this community, and the evidence for linkage to NRAMP1, a candidate gene for susceptibility to mycobacterial diseases, was assessed. Individuals were grouped into risk (liability) classes based on vaccination, age, previous disease, and tuberculin skin-test results. Under the assumption of a dominant mode of inheritance and a relative risk of 10, which is associated with the high-risk genotypes, a maximum LOD score of 3.81 was observed for linkage between a tuberculosis-susceptibility locus and D2S424, which is located just distal to NRAMP1, in chromosome region 2q35. Significant linkage was also observed between a tuberculosis-susceptibility locus and a haplotype of 10 NRAMP1 intragenic variants. No linkage to the major histocompatibility-complex region on chromosome 6p was observed, despite distortion of transmission from one member of the oldest couple to their affected offspring. The ability to assign individuals to risk classes was crucial to the success of this study.
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- 2000
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14. Low prevalence of psychoses among the Hutterites, an isolated religious community.
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Nimgaonkar VL, Fujiwara TM, Dutta M, Wood J, Gentry K, Maendel S, Morgan K, and Eaton J
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- Age of Onset, Bipolar Disorder epidemiology, Bipolar Disorder genetics, Canada epidemiology, Emigration and Immigration statistics & numerical data, Genetics, Population, Humans, Manitoba epidemiology, Neurotic Disorders epidemiology, Neurotic Disorders genetics, Prevalence, Schizophrenia epidemiology, Schizophrenia genetics, Sex Factors, United States epidemiology, Family, Founder Effect, Psychotic Disorders epidemiology, Psychotic Disorders genetics
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Objective: The authors estimated the prevalence of psychoses among the Hutterites in Manitoba, Canada, who lived in 102 communal farms or colonies. The study stemmed from an earlier epidemiological survey of North American Hutterite colonies (1950-1953), in which a low prevalence of psychoses was documented., Method: Psychiatrically ill individuals identified during the previous survey were rediagnosed with DSM-IV criteria. A current provincial health insurance claims database was queried anonymously for the period June 1992-May 1997, and the prevalence rate of disease among Hutterites, identified by distinctive surnames and unique postal addresses, was compared with the rate in the entire population of the province of Manitoba and in a comparison group of persons with Hutterite surnames but with addresses outside the Hutterite colonies., Results: The annual prevalence of schizophrenia among the communal Hutterites, estimated from the database search by using ICD-9 criteria, was consistent with the prevalence found in the prior epidemiological survey (annual mean of 1.2/1,000 population, compared with 1.3/1,000 in the prior survey). The database search yielded a significantly lower prevalence for schizophrenia and other functional psychoses among communal Hutterites as well as among the comparison group, compared to the total Manitoba population. There was also lower prevalence for affective psychoses and adjustment reaction disorders among the communal Hutterites, compared to the total Manitoba population. Rates for neurotic disorders were elevated both among the communal Hutterites and the comparison group., Conclusions: The prevalence of specific psychoses was reduced among the Hutterites, although neurotic disorders were more prevalent. These findings suggest some specificity, although possible artifacts such as ascertainment bias must be considered. Further research is needed to examine genetic and environmental factors that may contribute to reduced prevalence of specific psychoses among the Hutterites.
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- 2000
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15. Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families.
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Tonin PN, Mes-Masson AM, Futreal PA, Morgan K, Mahon M, Foulkes WD, Cole DE, Provencher D, Ghadirian P, and Narod SA
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- BRCA2 Protein, Canada, DNA Primers, Family, Female, France ethnology, Genes, Tumor Suppressor, Genetic Markers, Humans, Middle Aged, Polymerase Chain Reaction, BRCA1 Protein genetics, Breast Neoplasms genetics, Genes, BRCA1, Neoplasm Proteins genetics, Neoplasms, Second Primary genetics, Ovarian Neoplasms genetics, Point Mutation, Sequence Deletion, Transcription Factors genetics
- Abstract
We have identified four mutations in each of the breast cancer-susceptibility genes, BRCA1 and BRCA2, in French Canadian breast cancer and breast/ovarian cancer families from Quebec. To identify founder effects, we examined independently ascertained French Canadian cancer families for the distribution of these eight mutations. Mutations were found in 41 of 97 families. Six of eight mutations were observed at least twice. The BRCA1 C4446T mutation was the most common mutation found, followed by the BRCA2 8765delAG mutation. Together, these mutations were found in 28 of 41 families identified to have a mutation. The odds of detection of any of the four BRCA1 mutations was 18.7x greater if one or more cases of ovarian cancer were also present in the family. The odds of detection of any of the four BRCA2 mutations was 5.3x greater if there were at least five cases of breast cancer in the family. Interestingly, the presence of a breast cancer case <36 years of age was strongly predictive of the presence of any of the eight mutations screened. Carriers of the same mutation, from different families, shared similar haplotypes, indicating that the mutant alleles were likely to be identical by descent for a mutation in the founder population. The identification of common BRCA1 and BRCA2 mutations will facilitate carrier detection in French Canadian breast cancer and breast/ovarian cancer families.
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- 1998
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16. SMN(T) and NAIP mutations in Canadian families with spinal muscular atrophy (SMA): genotype/phenotype correlations with disease severity.
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Simard LR, Rochette C, Semionov A, Morgan K, and Vanasse M
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- Canada ethnology, Chimera, Cyclic AMP Response Element-Binding Protein, Exons genetics, Female, Genotype, Haplotypes, Humans, Introns genetics, Male, Muscular Atrophy, Spinal ethnology, Neuronal Apoptosis-Inhibitory Protein, Pedigree, Phenotype, RNA-Binding Proteins, SMN Complex Proteins, Gene Deletion, Muscular Atrophy, Spinal genetics, Nerve Tissue Proteins genetics
- Abstract
Childhood-onset spinal muscular atrophy (SMA) is an autosomal recessive neuropathy characterized by selective degeneration of alpha-motor neuron cells of the spinal cord. Age of onset and motor development varies greatly among patients, but the molecular basis of this variability remains unclear. The SMA locus contains two copies of a 500-kb element and deletions within the telomeric element have been shown to be the most common cause of SMA. To study the relationship between genotype and phenotype, 60 SMA families, all but two of which are of French Canadian origin, were screened for deletions in the telomeric survival motor neuron (SMN(T)) and the intact neuronal apoptosis inhibitory protein (NAIP) genes. Combining these results with those obtained for the multicopy microsatellite marker Ag1-CA (D5S1556) indicated that there are at least two types of SMA alleles. Most type I SMA patients are homozygous for large scale deletions involving the entire SMN(T) gene as well as exons 5 and 6 of the NAIP gene. The strong association between the 100-bp allele of Ag1-CA and large scale deletions in populations of diverse ethnic origin suggests that this allele marks an unstable or founder SMA chromosome. In contrast, most chronic SMA patients have at least one SMA allele with either an intragenic SMN(T) deletion or a SMN(C):SMN(T) chimeric gene which replaces the normal SMN(T) gene. The broad continuum of disease presentation in chronic SMA is most likely a consequence of the interaction between different SMA alleles.
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- 1997
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17. Limb-girdle muscular dystrophy and Miyoshi myopathy in an aboriginal Canadian kindred map to LGMD2B and segregate with the same haplotype.
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Weiler T, Greenberg CR, Nylen E, Halliday W, Morgan K, Eggertson D, and Wrogemann K
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- Adolescent, Adult, Age of Onset, Canada, Female, Haploidy, Humans, Male, Microsatellite Repeats, Pedigree, American Indian or Alaska Native genetics, Chromosomes, Human, Pair 2, Genetic Linkage, Muscular Dystrophies genetics
- Abstract
We report the results of our investigations of a large, inbred, aboriginal Canadian kindred with nine muscular dystrophy patients. The ancestry of all but two of the carrier parents could be traced to a founder couple, seven generations back. Seven patients presented with proximal myopathy consistent with limb girdle-type muscular dystrophy (LGMD), whereas two patients manifested predominantly distal wasting and weakness consistent with Miyoshi myopathy (distal autosomal recessive muscular dystrophy) (MM). Age at onset of symptoms, degree of creatine kinase elevation, and muscle histology were similar in both phenotypes. Segregation of LGMD/MM is consistent with autosomal recessive inheritance, and the putative locus is significantly linked (LOD scores >3.0) to six marker loci that span the region of the LGMD2B locus on chromosome 2p. Our initial hypothesis that the affected patients would all be homozygous by descent for microsatellite markers surrounding the disease locus was rejected. Rather, two different core haplotypes, encompassing a 4-cM region spanned by D2S291-D2S145-D2S286, segregated with the disease, indicating that there are two mutant alleles of independent origin in this kindred. There was no association, however, between the two different haplotypes and clinical variability; they do not distinguish between the LGMD and MM phenotypes. Thus, we conclude that LGMD and MM in our population are caused by the same mutation in LGMD2B and that additional factors, both genetic and nongenetic, must contribute to the clinical phenotype.
- Published
- 1996
18. Friedreich ataxia in Acadian families from eastern Canada: clinical diversity with conserved haplotypes.
- Author
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Richter A, Poirier J, Mercier J, Julien D, Morgan K, Roy M, Gosselin F, Bouchard JP, and Melançon SB
- Subjects
- Canada, DNA analysis, Female, Genetic Linkage genetics, Haplotypes, Humans, Male, Pedigree, Polymorphism, Genetic, Friedreich Ataxia genetics
- Abstract
The gene for Friedreich ataxia (FRDA), an autosomal-recessive neurodegenerative disease, remains elusive. The current candidate region of about 150 kb lies between loci FR2 and F8101 near the D9S15/D9S5 linkage group at 9q13-21.1. Linkage homogeneity between classical FRDA and a milder, slowly progressive Acadian variant (FRDA-Acad) has been demonstrated. An extended D9S15-D9S5 haplotype (C6) predominates in FRDA-Acad chromosomes from Louisiana. We studied 10 Acadian families from New Brunswick, Canada. In eight families, affected individuals conformed to the clinical description of FRDA-Acad; in one, 2 sibs presented with spastic ataxia (SPA-Acad). In the last family, 2 sibs had FRDA-Acad, and one had SPA-Acad. We found that SPA-Acad is linked to the FRDA gene region. The C6 haplotype and a second major haplotype (B7) were identified. The same ataxia-linked haplotypes segregated with both FRDA-Acad and SPA-Acad in two unrelated families. The parental origins of these haplotypes were different. Our observation of different phenotypes associated with the same combination of haplotypes may point to the influence of the parent of origin on gene expression, indicate the effect of modifier genes, or reflect the presence of different mutations on the same haplotypes. Our findings underline the need to investigate families with autosomal-recessive ataxias for linkage to the FRDA region, despite lack of key diagnostic manifestations such as cardiomyopathy or absent deep-tendon reflexes.
- Published
- 1996
- Full Text
- View/download PDF
19. Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families.
- Author
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Simard J, Tonin P, Durocher F, Morgan K, Rommens J, Gingras S, Samson C, Leblanc JF, Bélanger C, and Dion F
- Subjects
- Amino Acid Sequence, BRCA1 Protein, Base Sequence, Breast Neoplasms epidemiology, Canada epidemiology, DNA Primers, Female, Haplotypes, Humans, Male, Molecular Sequence Data, Ovarian Neoplasms epidemiology, Pedigree, Breast Neoplasms genetics, Frameshift Mutation, Neoplasm Proteins genetics, Ovarian Neoplasms genetics, Transcription Factors genetics
- Abstract
Women who carry mutations in the BRCA1 gene on chromosome 17q have an 85% lifetime risk of breast cancer, and a 60% risk of ovarian cancer. We have identified BRCA1 mutations in 12 of 30 (40%) Canadian families with breast and/or ovarian cancer, including six of the eight families (75%) that contained two cases of early-onset breast cancer and two cases of ovarian cancer. Six frameshift mutations account for all 12 mutant alleles, including nucleotide insertions (two mutations) and deletions (four mutations). Four independent families carried the same 1 basepair (bp) insertion mutation in codon 1755 and four other families shared a 2 bp deletion mutation in codons 22-23. These families were not known to be related, but haplotype analysis suggests that the carriers of each of these mutations have common ancestors.
- Published
- 1994
- Full Text
- View/download PDF
20. Association between Ag1-CA alleles and severity of autosomal recessive proximal spinal muscular atrophy.
- Author
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DiDonato CJ, Morgan K, Carpten JD, Fuerst P, Ingraham SE, Prescott G, McPherson JD, Wirth B, Zerres K, and Hurko O
- Subjects
- Alleles, Base Sequence, Canada epidemiology, Chromosome Mapping, Chromosomes, Human, Pair 5 genetics, Cosmids, Female, France ethnology, Genetic Linkage, Genetic Markers genetics, Haplotypes, Humans, Hybrid Cells, Male, Molecular Sequence Data, Muscular Atrophy, Spinal classification, Muscular Atrophy, Spinal ethnology, Polymerase Chain Reaction, Sequence Tagged Sites, Chromosome Aberrations genetics, Muscular Atrophy, Spinal genetics, Muscular Atrophy, Spinal pathology
- Abstract
The gene for autosomal recessive proximal spinal muscular atrophy (SMA) has been mapped to an 850-kb interval on 5q11.2-q13.3, between the centromeric D5S823 and telomeric D5S557 markers. We report a new complex marker, Ag1-CA, that lies in this interval, whose primers produce one, two, or rarely three amplification-fragment-length variants (AFLVs) per allele. Class I chromosomes are those which amplify a single AFLV allele, and class II chromosomes are those which amplify an allele with two or three AFLVs. Ag1-CA shows highly significant allelic association with type I SMA in both the French Canadian (Hôpital Sainte-Justine [HSJ]) and American (Ohio State University [OSU]) populations (P < .0001). Significant association between the Ag1-CA genotype and disease severity was also observed. Type I patients were predominantly homozygous for class I chromosomes (P = .0003 OSU; P = .0012 HSJ), whereas the majority of type II patients were heterozygous for class I and II chromosomes (P = .0014 OSU; P = .001 HSJ). There was no significant difference in Ag1-CA genotype frequencies between type III patients (P = .5 OSU; P = .25 HSJ) and the paired normal chromosomes from both carrier parents. Our results indicate that Ag1-CA is the most closely linked marker to SMA and defines the critical candidate-gene region. Finally, we have proposed a model that should be taken into consideration when screening candidate SMA genes.
- Published
- 1994
21. Linkage disequilibrium analysis of childhood-onset spinal muscular atrophy (SMA) in the French-Canadian population.
- Author
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Simard LR, Prescott G, Rochette C, Morgan K, Lemieux B, Mathieu J, Melançon SB, and Vanasse M
- Subjects
- Age of Onset, Canada, Child, Female, France ethnology, Genetic Linkage, Haplotypes, Humans, Male, Recombination, Genetic, Linkage Disequilibrium, Spinal Muscular Atrophies of Childhood genetics
- Abstract
Spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy, the most common neuromuscular disorder in childhood. The gene responsible for childhood SMA has been mapped to the q11.2-q13.3 region of chromosome 5. We have extended our linkage studies of SMA in the French-Canadian population to include microsatellite markers at the D5S125, D5S351, D5S435, JK53CA1/2 and MAP1B loci. These markers span about 4 cM of the SMA candidate region. We observed significant evidence for linkage between SMA and all the markers tested. The analysis of recombinant chromosomes provide evidence for the following genetic order: D5S125-D5S435-MAP1B-3'-JK53CA1/2 and places D5S351 proximal to JK53CA1/2. Furthermore, we confirm the current localization of the SMA gene distal to D5S435. Finally, we provide demonstration of significant linkage disequilibrium between childhood-onset SMA and four of the five marker loci, D5S125, D5S435, D5S351 and JK53CA1/2. Analysis of SMA-region haplotypes suggests that there may be a predominant SMA allele that is present on about 17% of SMA chromosomes in this sample of the French-Canadian population. We conclude that the observed linkage disequilibrium is likely due to genetic drift among regions of Quebec, consistent with this population's early history.
- Published
- 1994
- Full Text
- View/download PDF
22. Asbestos: the turbulent interface between science and policy.
- Author
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Morgan K
- Subjects
- Canada, Asbestos, Health Policy trends
- Published
- 1992
23. Linkage study of chronic childhood-onset spinal muscular atrophy (SMA): confirmation of close linkage to D5S39 in French Canadian families.
- Author
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Simard LR, Vanasse M, Rochette C, Morgan K, Lemieux B, Melançon SB, and Labuda D
- Subjects
- Canada, Chromosomes, Human, Pair 5, Chronic Disease, Female, France ethnology, Genetic Markers, Humans, Lod Score, Male, Pedigree, Genetic Linkage, Muscular Atrophy, Spinal genetics
- Abstract
Chronic childhood-onset spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy, the most common neuromuscular disorder in childhood. Recent linkage analyses have mapped this disease to 5q12-5q14. We show that chronic SMA (Types II and III) is tightly linked to the marker locus D5S39 (Zmax = 5.47 at theta = 0.02) in eight French Canadian families. In contrast to previously published results, we do not observe close linkage between chronic SMA and D5S6 (Zmax = 0.34 at theta = 0.18) or D5S78 (Zmax = 0.25 at theta = 0.21). Last, we present a family that appears to be discordant for this localization but may represent the first example of an incompletely penetrant individual.
- Published
- 1992
- Full Text
- View/download PDF
24. Cystic fibrosis mutations in the Hutterite Brethren.
- Author
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Klinger K, Horn GT, Stanislovitis P, Schwartz RH, Fujiwara TM, and Morgan K
- Subjects
- Base Sequence, Canada, Christianity, Chromosome Deletion, Cystic Fibrosis ethnology, Genetic Linkage, Haplotypes, Humans, Molecular Sequence Data, Oligonucleotide Probes, Polymerase Chain Reaction, United States, White People, Cystic Fibrosis genetics, Mutation
- Abstract
The presence or absence of the major cystic fibrosis (CF) mutation, delta F508, in the general patient population was determined by Kerem et al. using allele-specific oligonucleotides for the mutant and normal sequences in the polymerase chain reaction (PCR). delta F508 was identified by Riordan et al., and it is a 3-bp deletion of the phenylalanine codon at position 508. The Hutterite Brethren are an inbred North American population who have three different DNA marker haplotypes of CF chromosomes. Genomic DNA from both a CF child and one parent from each of 10 Hutterite families was analyzed for the presence or absence of the deletion mutation. delta F508 is associated with one of the three CF haplotypes in the Hutterite population, and this is the most common haplotype in a subset of the linkage family data of Kerem et al. The other two Hutterite CF haplotypes are generally rate in Caucasian populations. Since these two CF haplotypes do not carry the deletion mutation, they must carry a different CF mutation(s). The results of the PCR analysis for the deletion mutation lend additional support to our previous conclusion that there were at least three original carriers of CF mutations among the founders of the Hutterite population and that all copies of the same CF haplotype were identical by descent. One Hutterite CF patient has both of the haplotypes which do not carry delta F508. Analysis of this individual's DNA should allow identification of two additional CF mutations in this population.
- Published
- 1990
25. Patterns of cancer in geographic and endogamous subdivisions of the Hutterite Brethren of Canada.
- Author
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Morgan K, Holmes TM, Grace M, Kemel S, and Robson D
- Subjects
- Canada, Christianity, Demography, Female, Geography, Humans, Male, Neoplasms etiology, Registries, Smoking, Neoplasms epidemiology, Religion and Medicine
- Abstract
The Hutterite Brethren comprise a religious isolate and live on communal agricultural farms (colonies) in North America. In 1976 there were approximately 15,000 Canadian Brethren living in 179 colonies of the three endogamous subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. Dariusleut and Lehrerleut colonies are located in both Alberta and Saskatchewan, and the Schmiedeleut are in Manitoba. Brethren were identified on population-based cancer registries of the three Prairie Provinces and among death registrations in the vital statistics of Alberta and Saskatchewan. The method of ascertainment was by a search for the 15 contemporary surnames and verification by address. 89 male and 91 female Brethren were identified who had cancer during the period, 1956--1975. The numbers of observed cancers were less than expected from provincial incidence rates for males and females in each province. The largest deficits were for female Brethren in Manitoba and Saskatchewan. There is a marked deficiency of cancer of the uterine cervix among female Brethren. In males there is a significant deficit of lung cancer. The Hutterite way of life contributes to a low risk for cancers of smoking-associated sites. However, there is evidence that male Brethren in Alberta may be at relatively increased risk for stomach cancer and leukemias. The site distribution patterns of cancers among the three endogamous leut are similar.
- Published
- 1983
- Full Text
- View/download PDF
26. Cancer incidence in a religious isolate of Alberta, Canada, 1953-74.
- Author
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Gaudette LA, Holmes TM, Laing LM, Morgan K, and Grace MG
- Subjects
- Adolescent, Adult, Age Factors, Aged, Canada, Child, Female, Humans, Male, Middle Aged, Registries, Religion, Sex Factors, Stomach Neoplasms genetics, Ethnicity, Neoplasms epidemiology
- Abstract
Members of a religious isolate who live in approximately 240 farming colonies in the Canadian prairie provinces and the United States border states were studied. The sect's 6,700 members living in the province of Alberta, Canada, comprise more than 30% of this sect's population of North America. The numbers of their cancer cases ascertained from 1953 to 1974 in Alberta were compared to those expected from Alberta Cancer Registry rates. The overall incidence of registered cases of cancer among the religious isolate's females was significantly less than expected (48 observed, 74.2 expected), and in the males the overall incidence of cancer did not differ from that expected (52 observed, 56.5 expected). Significantly fewer cases of lung cancer than expected were found in males, and significantly fewer cases of carcinoma in situ of the cervix uteri were found in females. Finally, significantly higher incidence of stomach cancer was found in the sect's males. Data on a family with two cases of stomach cancer contributed to this observed excess of stomach cancer.
- Published
- 1978
- Full Text
- View/download PDF
27. Genealogical analysis of cystic fibrosis families and chromosome 7q RFLP haplotypes in the Hutterite Brethren.
- Author
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Fujiwara TM, Morgan K, Schwartz RH, Doherty RA, Miller SR, Klinger K, Stanislovitis P, Stuart N, and Watkins PC
- Subjects
- Canada, Chromosome Mapping, Genealogy and Heraldry, Genetic Linkage, Genetic Markers, Haplotypes, Humans, Pedigree, United States, White People, Chromosomes, Human, Pair 7, Cystic Fibrosis genetics, Genetics, Population, Polymorphism, Genetic, Polymorphism, Restriction Fragment Length
- Abstract
In the 100-year period 1880-1980 the Hutterite population increased from about 442 to 23,000 individuals in North America. There are three endogamous subdivisions in this Caucasian genetic isolate. A total of 11 cystic fibrosis (CF) families from Canada and the United States were investigated, including at least two families from each of the three subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. A study of RFLPs for the loci D7S8, D7S23, MET, and D7S18 (also called D7S16) in the region of the CF gene in 10 families shows considerable genetic variability. There were three different extended CF gene-region haplotypes on CF chromosomes (CF haplotypes), and there were 13 different extended CF gene-region haplotypes on normal chromosomes (normal haplotypes). The three CF haplotypes have different D7S23 and MET haplotypes. Parents who have the same CF haplotype are, on the average, more closely related than parents who have different haplotypes, but only within the same subdivision. A marriage node graph of 11 families illustrates the complexity of Hutterite genealogies. The frequency distribution of CF haplotypes in the Hutterite sample differs notably from those of larger agglomerates of family data from collaborative studies, with respect to D7S8, MET haplotypes, and D7S23 haplotypes. We propose that there were at least three CF carriers among the founders of the Hutterite population and that copies of a particular CF haplotype in current individuals are identical by descent. The alternative that one or more genetically distinguishable CF haplotypes resulted from recombination since the founding of the population is considered to be less likely.
- Published
- 1989
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