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1. |
Using loss of heterozygosity data in affected pedigree member linkage tests |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 339-350
Edward D. Lustbader,
Timothy R. Rebbeck,
Kenneth H. Buetow,
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摘要:
AbstractLinkage analysis can be used to test the hypothesis that a marker locus of known location segregates independently from a presumed disease gene. One way to test this hypothesis is to measure the similarity of marker alleles among pairs of relatives affected with the disease. When the disease under consideration is cancer, it is possible to take advantage of the marker alleles in tumors to revise the similarity measure obtained from the observations made in constitutional tissue. Only cancers that arise through the model of recessive oncogenesis are amenable to this revised analysis. This model postulates that cancer is caused by somatic genetic changes which result in the loss of one or both copies of a normal allele at a tumor suppressor locus. If an individual's inherited genotype is heterozygous at the marker locus, the model of recessive oncogenesis suggests that we may observe loss of constitutional heterozygosity at the marker locus in the tumor. In this report, we show how to incorporate this loss of heterozygosity data into affected pedigree member linkage tests. The revised procedure is illustrated using data obtained from relatives with breast cancer. Substantial improvement in the power to reject the different chromosome hypothesis is obtained when loss of heterozygosity is observed in multiple relatives with the same marker alleles retained in the tumors. ©1995 Wiley‐Liss, I
ISSN:0741-0395
DOI:10.1002/gepi.1370120402
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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2. |
Simulation study comparing interval estimates for the recombination fraction |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 351-359
Barbara Berger Nemesure,
David A. Greenberg,
Nancy R. Mendell,
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摘要:
AbstractThree interval estimation procedures were evaluated to determine the method which provides the most accurate estimates for the recombination fraction, θ. The lod–0.83 support interval, the jackknife confidence interval, and the confidence interval based on estimated asymptotic standard error were compared by calculating the coverage probabilities of each. Family data that were simulated under the model of a single fully penetrant, dominant disease locus at some distance, θ, from fully informative matings were used. Comparisons were based on 1,000 random samples of size 20, 60, and 100 families. In addition, a methodology for obtaining prediction intervals for θ was developed. This procedure is of practical use and does not require asymptotic assumptions based on large sample theory. The results provide an a priori idea about precision of the estimates, as well as empirical interval estimates of θ. Graphs of the authors' Monte Carlo intervals are presented for these simulations. Investigators studying different traits, however, could condition specifically on the family structure and distribution of the disease they are investigating and obtain similar graphs. ©1995 Wiley‐L
ISSN:0741-0395
DOI:10.1002/gepi.1370120403
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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3. |
Evaluating a new algorithm for linking maternal and newborn medical records |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 361-369
Kimberly R. Grace,
Grady Waters,
Carl A. Huether,
Lawrence D. Edmonds,
Phillip McClain,
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摘要:
AbstractLinking maternal and newborn medical records is a valuable tool for assessing the relationship between maternal variables and fetal outcome. This study evaluated the Center for Disease Control's newly developed maternal and newborn medical record linkage system, a computer program that uses weighted variables to determine the most likely maternal and newborn pairs. Any newborn record not achieving a set minimum score with a maternal record remains nonmatched. The objectives of the study were to estimate the program's matching accuracy, determine causes of incorrect matches and nonmatches, develop suggestions for program revisions, and evaluate the effects of the revisions. The study sample included 521 matched and 247 nonmatched maternal and newborn medical records from seven Ohio hospitals. Of all available newborn records (10,068), 574 (5.7%) did not match with maternal records; for those in which a match occurred, the authors ascertained a 98% matching accuracy and determined explanations for nonmatched and incorrectly matched records. The authors noted a greater prevalence of birth defects and prematurity among newborns with nonmatched records than among those with matched records. Program revisions, therefore, focused on reducing the prevalence of nonmatched records. The revised program reduced the prevalence of nonmatched records from 5.7% to 3% but reduced matching accuracy. ©1995 Wiley‐Liss, I
ISSN:0741-0395
DOI:10.1002/gepi.1370120404
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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4. |
No association of apolipoprotein A‐IV codon 347 and 360 variation with atherosclerosis and lipid transport in a sample of mixed hyperlipidemics |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 371-380
Maurita H. Carrejo,
A. Richey Sharrett,
Wolfgang Patsch,
Eric Boerwinkle,
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摘要:
AbstractGenetic variation at the apolipoprotein (apo) A‐I/C‐III/A‐IV gene cluster on chromosome 11 has been associated with differences in occurrence of atherosclerosis and with variability in lipid levels among hypercholesterolemic‐hypertriglyceridemic individuals. The functional cause of the association is not known, but polymorphisms of the apo A‐IV gene are of interest because apo A‐IV is involved in both triglyceride and cholesterol metabolism. Two mutations in the apo A‐IV gene, 347T→S and 360Q→H, are known to cause amino acid substitutions in the mature protein. These polymorphisms were typed in a sample of 119 subjects with high cholesterol and high triglycerides in whom carotid artery wall thickness was previously shown to be strongly associated with silent polymorphic variation in the A‐I/C‐III/A‐IV gene cluster.The relative allele frequencies were 0.83 and 0.17 for codon 347T→S, and 0.95 and 0.05 for codon 360Q→H. These polymorphisms did not show a statistically significant relationship with prevalent hypertension, diabetes, or cardiovascular disease or with plasma lipid levels. Most importantly, these amino acid substitutions in apo A‐IV were not associated with carotid artery wall thickness. Therefore, the genetic cause of disease variability in a sample of mixed hyperlipidemics is not amino acid substitutions in codons 347 or 360 of the apolipoprotein A
ISSN:0741-0395
DOI:10.1002/gepi.1370120405
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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5. |
Polymorphism at VNTR Locus 3′ to the apolipoprotein B gene in a tunisian population: Difference from other ethnic groups |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 381-389
Catherine Buresi,
Eric Desmarais,
Suzanne Vigneron,
Chiheb Ben Rayana,
Habiba Chaabouni,
Gérard Roizes,
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摘要:
AbstractThe Hypervariable Region (HVR) detected at the 3′ end of the apolipoprotein B (Apo B) locus has been the subject of numerous studies. As for many VNTR (variable number of tandem repeat), this locus is highly polymorphic and until now about 20 alleles have been described. The genotype distribution in all populations follows the Hardy‐Weinberg predictions. A bimodal pattern of allele frequency distribution is apparent in all Caucasoid populations. We have analyzed the frequencies of different alleles in a Tunisian population (123 individuals) by the polymerase chain reaction technique and compared our results to those obtained in several ethnic groups. It appears that the distributions of the allele frequencies are very different: for Caucasoid populations, there are two peaks of frequencies for alleles with 36 and 48 repeats, but alleles of intermediate lengths are more frequent. Hixson et al. [(1993)Hum Genet91:475–479] have shown a similar difference between black and white American populations. We found the same results in a black African group.Some of the repeat units of this HVR contain a Ssp I restriction site and digestion of the PCR products by this enzyme gives different patterns on gradient acrylamide gel [Desmarais et al., 1993,Nucleic Acids Res21:2179–2184.] The DNA of African individuals (42) has been analyzed to discover the origin of this new allele. Preliminary results indicate that these particular alleles probably arose by introgression from the African population into the Tunisian one. ©1995 Wiley
ISSN:0741-0395
DOI:10.1002/gepi.1370120406
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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6. |
Angiotensin‐converting enzyme genotypes in the high‐ and low‐risk area for coronary heart disease in Finland |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 391-399
Markus Perola,
Antti Sajantila,
Cinzia Sarti,
Jari Stengård,
Markku Tamminen,
Pekka Puska,
Jussi Huttunen,
Jaakko Tuomilehto,
Leena Peltonen,
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摘要:
AbstractThe deletion/deletion genotype of the insertion (I)/deletion (D) polymorphism of the angiotensin‐converting enzyme (ACE) gene has been suggested to be a risk factor for myocardial infarction (MI). The objective of this study was to evaluate whether genotypic distributions of the I/D polymorphism of the ACE gene are different between individuals from high‐risk and low‐risk areas for coronary heart disease in the genetically isolated population of Finland and to assess the impact of this genetic risk factor by comparing individuals with different parental histories of MI. Representative population‐based samples of middle‐aged men (n= 363) and women (n= 358) from two areas of Finland were used. The area had a borderline significant effect on the prevalence of the genotype DD (β = 0.35, SE = 0.16, χ2= 4.70, df = 1,P= 0.03), the DD genotype being more prevalent in eastern Finland (the high‐risk area). The II genotype was more prevalent in women with parental history of MI, so we could not replicate the previous findings of the risk‐increasing effect of DD genotype in this sample. Although the observed difference in the ACE DD genotype between the high‐risk and low‐risk areas for coronary heart disease might represent one of the genetic factors contributing to the difference in risk of coronary heart disease between eastern and southwestern Finland, the data emphasize the fact that also other risk factors, including other genes, contribute to this difference and the high incidence of MI in Finland. ©
ISSN:0741-0395
DOI:10.1002/gepi.1370120407
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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7. |
Segregation analysis of breast cancer in a population‐based sample of postmenopausal probands: The Iowa women's health study |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 401-415
Ping‐Ling Chen,
Thomas A. Sellers,
Stephen S. Rich,
John D. Potter,
Aaron R. Folsom,
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摘要:
AbstractInheritance of a major susceptibility gene for breast cancer has been primarily investigated in families with early‐onset disease. However, familial clustering of late‐onset breast cancer is well documented, and genetic factors may also be relevant. In the Iowa Women's Health Study, we evaluated evidence for a major gene after allowing for measured environmental risk factors. Two hundred sixty‐five incident breast cancer probands were identified from a prospective cohort study of 41,837 women aged 55 to 69 years at baseline in 1986. A pedigree development form was mailed to the probands to ascertain all first‐degree female relatives. A questionnaire and body measurement protocol were mailed to identified living relatives or surrogates. Segregation analyses were conducted on a total of 1,145 women in 251 families using regressive models as implemented in S.A.G.E. Mendelian codominant inheritance of an allele that produced an earlier age‐at‐onset provided the best fit to the data. Incorporation of measured environmental risk factors as covariates yielded no significant improvements in the likelihoods. Approximately 50% of this population could be expected to carry a late‐onset breast cancer susceptibility gene, and 23% of the population is susceptible because of the environment in which they live. Homozygous gene carriers are predicted to have a mean age‐at‐onset of 48 years, over 20 years earlier than heterozygotes; few cases would be expected among non‐gene carriers. In conclusion, the transmission pattern of late‐onset breast cancer may be determined by a common susceptibility gene.
ISSN:0741-0395
DOI:10.1002/gepi.1370120408
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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8. |
Epidemiologic and genetic follo‐up study of 544 Minnesota breast cancer families: Design and methods |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 417-429
Thomas A. Sellers,
V. Elving Anderson,
John D. Potter,
Susan A. Bartow,
Ping‐Ling Chen,
Lenore Everson,
Richard A. King,
Christopher C. Kuni,
Lawrence H. Kushi,
Paul G. McGovern,
Stephen S. Rich,
Jan Whitbeck,
Georgia Wiesner,
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摘要:
AbstractIn 1944, a case‐control family study was initiated at the Dight Institute for Human Genetics at the University of Minnesota to study the influences of childbearing, breastfeeding, and hereditary susceptibility on the occurrence and age‐of‐onset of breast cancer. Index cases (probands) were women ascertained at the Tumor Clinic of the University of Minnesota Hospital. Medical history and life style information were obtained on probands and relatives, and all cancers were histologically verified. A total of 544 families were studied, with probands diagnosed between 1931 and 1952. All of the records and pathology slides have been maintained from the original study; for most probands this includes the original tissue blocks.We are conducting a historical cohort study of selected first‐ and second‐degree female relatives (sisters, daughters, nieces, granddaughters) of the probands and a group of control women identified as the spouses of all male first‐ and second‐degree relatives (brothers, sons, grandsons, and nephews). The subsequent development of breast cancer is being determined to quantify the absolute risk associated with a positive family history. Current disease status is ascertained with mammography, and stromal density is measured using digital imaging. Segregation analysis will be applied to examine how non‐genetic factors such as diet, exogenous hormone use, and body fat distribution influence risk in women at high risk because of family history. A subset of families are being selected for molecular analysis of the BRCA1 gene or for linkage analyses to identify putative susceptibility loci other than BRCA1. Documented cancer histories were known for at least three generations, and the current study extends the pedigrees up to four or five generations for every family, allowing a detailed description of familial risk.This cohort study of breast cancer families is likely to be important in both quantity and quality of data and will serve as a major genetic epidemiologic resource, being free of selection bias and having relevant non‐genetic exposure determined in at least four generations. ©19
ISSN:0741-0395
DOI:10.1002/gepi.1370120409
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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9. |
Cystic fibrosis: Current topics, J.A. Dodge, D.J.H. Brock, and J.H. Widdicombe, eds., New York: John Wiley&Sons, 1994, 354 pages, $99.95 |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 431-432
Giovanni Romeo,
Luis J. V. Galietta,
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ISSN:0741-0395
DOI:10.1002/gepi.1370120410
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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10. |
Assessing genetic risks. Implications for health and social policy, Lori B. Andrews, Jane E. Fullarton, Neil A. Holtzman, and Arno G. Motulsky, eds., Washington, DC: National Academy Press, 1994, 307 pages, $44.95 |
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Genetic Epidemiology,
Volume 12,
Issue 4,
1995,
Page 433-438
John C. Fletcher,
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ISSN:0741-0395
DOI:10.1002/gepi.1370120411
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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