摘要:

AbstractHuman apolipoprotein A‐IV (apoA‐IV) exhibits a genetically determined structural polymorphism amenable to analysis by isoelectric focusing and immunoblotting techniques. We have determined the allele frequency and molecular basis of a uniqueApoA‐IV*5allele which is widely distributed among blacks but is absent in other populations. The frequency of theApoA‐IV*5allele in blacks (N = 308) was estimated to be 3.2%. In comparison to the commonApoA‐IV*1allele, analysis of coding and non‐coding sequences of theApoA‐IV*5allele revealed an in‐frame insertion of 12 nucleotides near the carboxyl terminal region of the mature protein. The insertion involves an exact duplication of the second of the four repeats and codes for 4 amino acids glutamic acid (GAA), glutamine (CAG), glutamine (CAG), and glutamine (CAG) and is responsible for the charge shift of the the apoA‐IV 5 isoform slightly toward the anode as compared to the wild type apoA‐IV 1 isoform on the isoelectric focusing gel. This in‐frame insertion occurs in a region which is highly conserved among rat, mouse, and humans. In addition to the 12 nucleotide insertion, the four individuals sequenced for theApoA‐IV*5allele also revealed a same‐sense mutation by replacing G to T at the third position of codon 316. Our preliminary data suggest that this unqiue black allele marker may be of potentially significance in studies of human lipid metabolism and in microevolutio

ISSN:0741-0395    

DOI:10.1002/gepi.1370090602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractA segregation analysis using a regressive model with generation‐ and age‐dependent effects was applied to familial data of height‐adjusted weight to investigate the major gene hypothesis. The sample included 629 nuclear families with 2,534 members volunteering for a free health check‐up in the Preventive Medicine Center of Vandoeuvre‐lès‐Nancy, France. The familial correlations were 0.094 ± 0.040 between spouses, 0.198 ± 0.023 between parent and offspring, and 0.327 ± 0.034 between siblings. The variability of the trait was higher in parents than in offspring. The most parsimonious genetic model indicated a codominant major effect increasing with age in childhood, then stabilizing in adulthood. The same data were analyzed using the classical mixed model, assuming equality of variances between parents and offspring, no resemblance between spouses, similar parent–offspring and sib–sib correlations, and identical effects in parents and offspring. This analysis indicated a recessive solution. In both analyses, mendelian transmission was rejected. However, the mixture of two distributions in the recessive model, instead of three in the codominant one, was less constraining with respect to the test of transmission probabilities, and the rejection of mendelian transmission was due to a single family in the recessive case, instead of several families in the codominant one. This could possibly explain why previous studies, all using the mixed model, found evidence for a recessive major gene. Although the major gene hypothesis cannot be definitely ruled out from our results, the mechanism appears more complex than the effect of one single gene. ©

ISSN:0741-0395    

DOI:10.1002/gepi.1370090603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe relationship between ABO blood phenotype and total serum cholesterol (TC) level was examined in a Japanese population to determine whether an elevated TC level is associated with phenotype A, as has been demonstrated in many West European populations. Such studies in nonwhite populations are scarce, and findings generally failed to demonstrate the relationship. Inconsistent results from cross‐sectional studies of various racial groups with widely varying ages raised an age effect as a possible explanatory factor. It was also suggested that the ABO–TC association may not be apparent in populations with low fat intake or low mean cholesterol level. These hypotheses are addressed by examining long‐term TC data collected serially from the unexposed controls of the atomic bomb survivors in Hiroshima and Nagasaki who were participants of the Adult Health Study program at the Atomic Bomb Casualty Commission‐Radiation Effects Research Foundation between 1958 and 1986. The statistical method of growth curve analysis, through the mixed effect model of Laird and Ware [1982], was used to model age‐dependent changes in cholesterol levels within individuals. The effects of the ABO polymorphism in modifying the resultant growth curve are examined. We demonstrate that TC levels are elevated on average by about 4 mg/dl in phenotype A compared to non‐A in the Japanese (P<0.00001), and that this relationship is maintained from early to late adulthood, independent of sex, body mass index, cohort status, or city of residence. Thus, phenotype A individuals may be more predisposed to cardiovascular disease through one of its major risk factors. This is the first study of the ABO–cholesterol association in the Japanese, and the first based on a cohort with longitudinally collected TC data. © 1992 W

ISSN:0741-0395    

DOI:10.1002/gepi.1370090604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractSegregation analysis of discrete traits can be conducted by the classical mixed model and the recently introduced regressive models. The mixed model assumes an underlying liability to the disease, to which a major gene, a multifactorial component, and random environment contribute independently. Affected persons have a liability exceeding a threshold. The regressive logistic models assume that the logarithm of the odds of being affected is a linear function of major genotype effects, the phenotypes of older relatives, and other covariates. A formulation of the regressive models, based on an underlying liability model, has been recently proposed. The regression coefficients on antecedents are expressed in terms of the relevant familial correlations and a one‐to‐one correspondence with the parameters of the mixed model can thus be established. Computer simulations are conducted to evaluate the fit of the two formulations of the regressive models to the mixed model on nuclear families. The two forms of the class D regressive model provide a good fit to a generated mixed model, in terms of both hypothesis testing and parameter estimation. The simpler class A regressive model, which assumes that the outcomes of children depend solely on the outcomes of parents, is not robust against a sib–sib correlation exceeding that specified by the model, emphasizing testing class A against class D. The studies reported here show that if the true state of nature is that described by the mixed model, then a regressive model will do just as well. Moreover, the regressive models, allowing for more patterns of family dependence, provide a flexible framework to understand gene–environment interactions in complex diseases. © 1992 Wiley

ISSN:0741-0395    

DOI:10.1002/gepi.1370090605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370090601

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY