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1. |
Combining two‐point genetic linkage analyses using mapping functions |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 1-17
Daniel J. Schaid,
Robert C. Elston,
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摘要:
AbstractA likelihood ratio statistic is proposed for combining two‐point genetic linkage analyses when the two‐point analyses are between a trait and a well‐defined map of markers. It is assumed that the two‐point analyses are independent, as in the case of choosing only the most informative marker per family. The asymptotic distribution of the likelihood ratio statistic is derived under the null hypothesis of no linkage of the trait with a map of 2 markers, with intermarker genetic distance δ. This distribution is shown to be a chi‐square mixture distribution with mixing probability depending on δ and the assumed mapping function. We use this asymptotic result to approximate the distribution of the likelihood ratio statistic for the more general case of more than 2 markers. Simulation results indicate that this may be reasonable. Power is evaluated by simulations and results indicate that this approach, which constrains the intermarker distances to their known values, tends to be more powerful than other methods proposed in the literature. © 1994 Wil
ISSN:0741-0395
DOI:10.1002/gepi.1370110102
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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2. |
Influence of polymorphisms for apolipoprotein B (ins/del,Xbal,EcoRI)and apolipoprotein E on serum lipids and apolipoproteins in a Javanese population |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 19-27
B. Gajra,
J. K. Candlish,
N. Saha,
C. K. Heng,
A. G. Soemantri,
J. S. H. Tay,
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摘要:
AbstractA total of 231 healthy subjects from a central Javanese population were investigated for the distribution of three apolipoprotein B (apo B) polymorphisms (ins/del,XbaI, andEcoRI), as well as apolipoprotein E (apo E) polymorphism in relation to serum lipid and apolipoprotein concentrations. The frequencies of the rarer alleles (del, 0.09;X+, 0.1; andR−, 0.06) were lower than have been found for some Asian and European populations. Distribution of genotypes was in Hardy‐Weinburg equilibrium for all the polymorphisms. A linkage disequilibrium was observed only between theins/delandXbaI site polymorphisms of apo B (χ42= 25.3;P<0.001) consistent with that observed in some other population studies. No polymorphism of the apo B gene had an association with serum lipid or apolipoprotein concentrations in this population except forXabI, which appeared to be associated with serum TG (as the log transform:R2= 8.3;F= 4.8;P<0.01). The apo E4 allele was found to be associated with significantly higher serum total cholesterol (TC) and low‐density lipoprotein cholesterol (LDLC). Apo E polymorphism explained 5.9% of the sample variance of serum LDLC (F= 5.4;P<0.01). © 1994 Wiley‐
ISSN:0741-0395
DOI:10.1002/gepi.1370110103
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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3. |
Linkage between the APOB gene and serum apoB levels in a large pedigree from the Bogalusa heart study |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 29-40
A. E. Laing,
C. I. Amos,
C. DeMeester,
A. Diep,
Y. R. Xia,
R. C. Elston,
S. R. Srinivasan,
G. S. Berenson,
A. J. Lusis,
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摘要:
AbstractMaximum likelihood linkage analyses were performed to test for linkage between serum apoB levels and several candidate gene markers including apolipoprotein B, lipoprotein lipase, hepatic lipase, cholesterol ester transfer protein, and apolipoprotein AI in a large pedigree. Parameters of general Mendelian inheritance derived from maximum likelihood segregation analysis of the serum apoB levels were used in the linkage analysis. The highest two‐point lod score between the quantitative trait and a marker defined by a single restriction digest was 1.86 at recombination fraction (θ) = 0. This was observed for linkage between serum apoB levels and the presence or absence of a PvuII digestion site in the apoB gene. Linkage between serum apoB levels and polymorphisms of the apoB gene defined by the two restriction digests EcoR1 and PvuII was supported by a lod score of 3.30, while inclusion of VNTR typings led to a lod score of 2.33. None of the other candidate genes gave positive evidence of linkage. © 1994 Wiley‐Liss, Inc.This article is a US government work and, as such, is in the public domain in the United States of Am
ISSN:0741-0395
DOI:10.1002/gepi.1370110104
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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4. |
Some empirical properties of an all‐relative‐pairs linkage test |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 41-49
Jane M. Olson,
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摘要:
AbstractOlson and Wijsman [Genet Epidemiol 10:87–102, 1993] recently proposed a single test of linkage which combines information from different types of relative pairs in a pedigree. Relative‐pair‐type‐specific regression parameters that relate the squared pair trait difference to the estimated number of marker genes shared identical by descent between the pair are estimated using generalized estimating equation methodology, then combined to give a single linkage test statistic. Questions remain concerning the small sample and robustness properties of this test statistic; these questions are addressed in the present paper using simulation. The test is substantially anti‐conservative for samples with fewer than about ten families and are approximately valid for samples larger than about 15 families. In addition, the test appears robust in the presence of trait genotype by environment interaction, trait family‐specific errors, a second major trait locus, and trait dominance. Surprisingly, the sibpair test was more powerful than the all‐relative‐pairs test for dominant traits with high heritability. Finally, adjusting for the presence of a marker known to be linked to one trait locus only marginally improves the power for detecting a second trait locus. © 1994
ISSN:0741-0395
DOI:10.1002/gepi.1370110105
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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5. |
Sibling correlations and segregation analysis of age‐related maculopathy: The beaver dam eye study |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 51-67
Ibrahim M. Heiba,
Robert C. Elston,
Barbara E. K. Klein,
Ronald Klein,
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摘要:
AbstractSibling correlations were evaluated and segregation analysis was performed on age‐dependent maculopathy scores of the right and left eyes of individuals from 564 families in the Beaver Dam Eye study. There is evidence of significant sibling correlations. The data fit a mixture of two normal distributions, especially after undergoing the Box and Cox power transformation. In each eye, the hypothesis of mendelian transmission of a major effect cannot be rejected under the τ'ABfree model, but is rejected under the τ's free model. The hypothesis of a random environmental major effect is rejected. Similar major gene parameter estimates are found for both eyes. The results are consistent with a major effect accounting for 62% and 59%, in the right and left eyes, respectively, of the determination of age‐related maculopathy scores. A single major gene can account for about 89% and 97% of this variability due to a major effect, or for about 55% and 57% of the total variability, in the right and left eyes, respectively. © 1994 Wiley‐L
ISSN:0741-0395
DOI:10.1002/gepi.1370110106
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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6. |
Improved programs for the affected‐pedigree‐member method of linkage analysis |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 69-74
Mark Schroeder,
Deborah L. Brown,
Daniel E. Weeks,
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ISSN:0741-0395
DOI:10.1002/gepi.1370110107
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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7. |
Epidemiologic analysis of gene‐environment interaction in twins |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 75-86
Ruth Ottman,
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摘要:
AbstractOur aim was to develop a simple method for testing gene‐environment interaction in twin data ascertained through affected twins (probands), with known exposure status of both cotwins. To this end we derived formulae for two epidemiologic measures, as a function of prevalence of an exposure and genotype, and disease risk conditional on exposure and genotype: (1) relative risk of disease in exposed vs. unexposed cotwins, stratified by zygosity and proband exposure status (RRE), and (2) relative risk of disease in MZ vs. DZ cotwins, stratified by exposure status of proband and cotwin (RRZ). Then we investigated the behavior of these two measures under different assumptions about the relations between exposure and genotype in terms of their effect on disease risk. If an exposure has a different effect in the presence vs. absence of the genotype, RREdiffers between MZ and DZ cotwins. Similarly, if a genotype has a different effect in exposed vs. unexposed persons, RRZdiffers between exposed and unexposed cotwins. However, large differences in RREbetween MZ and DZ cotwins, or large differences in RRZbetween exposed and unexposed cotwins, do not occur except under very extreme conditions, such as a genotype that increases disease risk in exposed individuals, and has a protective effect in unexposed individuals. These results suggest that power to detect gene‐environment interaction is limited with this approach. Conversely, if large differences in RREor RRZare observed, they are likely to reflect strong gene‐environment interaction. © 1994 Wiley‐L
ISSN:0741-0395
DOI:10.1002/gepi.1370110108
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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8. |
Labman and Linkman: A data management system specifically designed for genome searches of complex diseases |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 87-98
Phillip Adams,
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摘要:
AbstractTwo programs have been developed to manage linkage analysis data. The first program, LABMAN, is a comprehensive laboratory data management system organizing pedigrees, blood DNA samples, DNA markers, Southern blot or polyacrylamide gels, autoradiographs, and marker‐allele typings generated from these samples. Output includes mendelization checks for genetic incompatibilities in typings and formatted files ready for linkage analysis. LABMAN can also compress highly polymorphic allele systems into smaller allele systems facilitating analysis of large systems. The second program, LINKMAN, provides data management for lod score output from linkage analyses. It reads linkage analysis output files, calculates lod scores by family, associates lod scores with specific marker and family identifiers, and stores these data in a database where they can be combined with lod scores from previous analyses. LINKMAN easily incorporates any of a wide variety of genetic models. It produces formatted output of lod scores by user‐specified criteria for reports or as ASCII files for input to other programs. If desired, tests of homogeneity of linkage across families can be run via the HOMOG program [Ott, 1991] and their output included in reports.The programs include features critical for conducting genome searches of complex diseases: They are easy‐to‐use, well‐tested, and reliable. Data from multi‐center investigations can be easily combined for analysis. Moreover, they include extensive error‐checking capabilities, and they are specifically set up to protect blindness between laboratory workers and data analysts. LABMAN and LINKMAN are currently available free of charge under DOS. © 1994 W
ISSN:0741-0395
DOI:10.1002/gepi.1370110109
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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9. |
Erratum |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 99-99
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ISSN:0741-0395
DOI:10.1002/gepi.1370110110
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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10. |
Announcement |
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Genetic Epidemiology,
Volume 11,
Issue 1,
1994,
Page 100-100
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ISSN:0741-0395
DOI:10.1002/gepi.1370110111
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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