摘要:

AbstractWe have previously reported a large Israili‐Arab pedigree with sensorineural deafness possibly determined simultaneously by two loci‐one mitochondrial, and one autosomal recessive. This was analyzed by extending classic segregation analysis methods to the many nuclear families derived from the maternal line pedigree. Here we expand this pedigree and extend our analysis by using the regressive models for segregation analysis on the entire pedigree. The corresponding REGD computer program was utilized and the marrying‐in males' and paternal line members' affection statuses were assigned as unknown to accommodate the exclusive maternal transmission pattern. For the autosomal locus, a simple autosomal recessive (q= 0.52) model with a nearly complete penetrance (0.93) was found to be the regressive models to test the hypothesis of mitochondrial mutation occurred in a heteroplasmic distribution in the family members, this could not explain the familial aggregation in this pedigree, and an autosomal recessive locus is still required. These results provide further support for the concept that the sensorineural deafness occurring in this large Israeli‐Arab pedigree results from simultaneous involvement of two genes at two different loci, one mitochondrial and likely homoplasmic, and the other autosomal and recessive. © 1993 Wiley

ISSN:0741-0395    

DOI:10.1002/gepi.1370100102

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

年代:1993

数据来源: WILEY

摘要:

AbstractAutosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) is a disorder that has an elevated frequency in Saguenay‐Lac‐St‐Jean (SLSJ) and Charlevoix, two geographically isolated regions in the past of northeastern Quebec. The incidence at birth and the carrier rate in SLSJ were estimated at 1/1,932 liveborn infants and 1/22 inhabitants, respectively, for the period 1941‐‐1985. The mean inbreeding coefficient was twice higher and the mean kinship coefficient 3 times higher among the ARSACS families than among control families. In the SLSJ region, the birth places of the ARSACS individuals and their parents did not show a clustered distribution. The genealogical reconstruction suggests that the high incidence of ARSACS in SLSJ and Charlevoix is likely to be the result of a founder effect. Because the disease is apparently unknown elsewhere in the world and a high proportion of French Canadians presently living in eastern Quebec have ancestors coming from Perche, a small region in France, it also suggests that a unique mutation accounts for most, if not all, of the ARSACS cases known in these regions. © 1993 Wil

ISSN:0741-0395    

DOI:10.1002/gepi.1370100103

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

年代:1993

数据来源: WILEY

摘要:

AbstractAllelic variation at the apolipoprotien E (Apo E) structural locus has been shown to influence concentrations of total cholesterol and low density lipoprotein cholesterol (LDL‐C). Apo E has six phenotypes resulting from three common alleles at this locus. The ϵ2 allele is associated with lower LDL‐C and the ϵ4 allele with higher LDL‐C. In the current study, we compared the ϵ allele distribution in two cohorts of white women recruited from population based listing of southwestern Pennsylvania. The “younger” cohort consisted of 473 women, age 42–50; the “older” cohort, 870 women, age 65–90. A comparison of the overall distribution of allele frequencies in the two cohorts was significantly different. The allele frequency of ϵ4 was lower in the older cohort (0.98 vs. 0.122,P= 1.08) and the ϵ2 allele frequency was higher (0.084 vs. 0.059,P= 0.05) in the older cohort. These observations are consistent with the hypothesis that there may be a selection against individuals with the ϵ4 allele. However, future research is needed to confirm this observation and to compare survival in individuals by their ϵ allele

ISSN:0741-0395    

DOI:10.1002/gepi.1370100104

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

年代:1993

数据来源: WILEY

摘要:

AbstractSeveral studies raise the possibility that smoking during pregnancy is associated with a slightly decreased odds of trisomy 21 at birth. If it is, associations may reflect decreased incidence at conception, increased intrauterine loss (at one or several times in gestation), or both. Women ( n = 13,729) undergoing prenatal diagnosis completed a questionnaire before learning karyotype results. For each women with a trisomy, up to 4 controls with chromosomally normal pregnancies, matched for age and hospital, were selected. Analyses drew on the 89 trisomy 21‐control matched m‐tuples in which diagnosis was by amniocentesis at 14‐26 weeks. We compared the odds of smoking at last menstrual period and in the past in cases and controls. The odds of current smoking versus never smoking were decreased [adjusted odds ratio = 0.8, 95% confidence interval (CI) 0.4‐1.6]; and the odds of exsmoking increased (adjusted odds ratio = 1.4, 95% CI 0.9‐2.4) in trisomy 21 cases. The association with current smoking was essentially unchanged when the unexposed reference group was defined as exsmokers and women who never smoked (adjusted odds ratio = 0.7, 95% CI 0.4‐1.4). These results for current smoking agree well with a summary estimate based on combined studies of births. One interpretation is that at amniocentesis, as has been reported for births, current smoking is associated with a slightly decreased odds of trisomy 21. If associations at amniocentesis and birth are of equal magnitude, the explanation that observations at birth reflect increased loss in the second half of pregnancy with current smoking is unlikely to be correct. However, the present amniocentesis evidence supports this interpretation weakly and is insufficient to rule out the null hypothesis that smoking is unrelated to trisomy 21. © 1993 Wil

ISSN:0741-0395    

DOI:10.1002/gepi.1370100105

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

年代:1993

数据来源: WILEY

摘要:

AbstractSince many disorders have a variable age at onset, knowing the age at onset distribution of a disease facilitates epidemiologic analyses in several ways. The age at onset distribution is commonly used to estimate morbidity risks or the recurrence risks in genetic counseling. Unfortunately, estimation of a disease's age at onset distribution is not straightforward. The observed age at onset distribution obtained from prevalent cases is usually used in these epidemiologic analyses. Through simulation studies, we show that, in certain situations, the observed age at onset distribution has a non‐negligible downward bias. This bias can lead to a substantial underestimation of the morbidity risk or the recurrence risk. The simulations also demonstrate that a non‐parametric approach for correcting the age at onset distribution works well even when mortality increases after onset. The results have implications for diseases that have adult onset and/or increased mortality after onset. We suggest that researchers should use corrected age at onset distributions, rather than relying on observed distributions, in the calculation of either morbidity risks or recurrence risks. © 1993 Wiley‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370100106

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

年代:1993

数据来源: WILEY

摘要:

AbstractThis paper discusses the application of estimating equations methods based on a quadratic exponential model [Prentice and Zhao, 1991] as a potential competitor with full likelihood approaches to estimating the effect of major genes in a segregation analysis [Elston, 1981]of continuous phenotypes, in the single allele problem. We show that while the estimating equations methods based on the quadratic exponential family cannot be used by themselves to estimate all parameters of interest, an iterative two‐stage approach can be used, in which the population allele frequency is first considered to be a known parameter, which permits the estimating equations method to estimate the remaining parameters. At the second stage a “pseudo‐profile” loglikelihood based only on the founders is used to estimate the allele frequency. After each maximization of the pseudo‐profile loglikelihood at the second stage, the parameters in the first stage are reestimated using a new value of the allele frequency, and a new value of the second stage pseudo‐profile loglikelihood is obtained. We used simulated pedigree data for illustrations. © 1993 Wil

ISSN:0741-0395    

DOI:10.1002/gepi.1370100107

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe admixture test for the detection of linkage under heterogeneity is considered. We show that the null distribution of this test statistic has half its weight concentrated on zero and the other half on a complicated distribution that can be approximated by max (X1,X2) whereX1andX2are independent χ 12variables. We also investigate the stability of the size of the test for small samples. The power of this test to detect linkage, when heterogeneity is present, can be substantially greater than the standard test that assumes homogeneity. Even when heterogeneity is not present, the test is only slightly less powerful than the homogeneous test. This would suggest the use of the admixture test in preference to the homogeneous test if the presence of heterogeneity is at all suspected. © 1993 Wiley‐Liss

ISSN:0741-0395    

DOI:10.1002/gepi.1370100108

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

年代:1993

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370100109

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

年代:1993

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370100101

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

年代:1993

数据来源: WILEY