摘要:

AbstractSeveral dominant genetic diseases which appear to be homogeneous are the expression of genetic mutations at several loci. The power to detect linkage by likelihood methods is diminished for heterogeneous, as compared to genetically homogeneous, disorders. Using a simulation approach and two pedigrees typical of those available for the study of a dominant disease (with expected lod scores of 0.43 and 1.00 at θ = 0.05 and PIC = .59), I have evaluated the power to detect genetic heterogeneity by using the admixture test. Linkage power was determined by varying the number of families available for study, the recombination fraction (θ), the informativity of the hypothetical marker, and the proportion of linked families, α. For moderate and small values of α it is feasible to detect genetic heterogeneity once linkage has been established; rarely will it be possible to detect linkage and heterogeneity simultaneously given a limited number of small or moderate pedigr

ISSN:0741-0395    

DOI:10.1002/gepi.1370080402

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe Medical Birth Registry of Norway carries out a population‐based surveillance of birth defects on a routine basis. An increased proportion of newborn with Down syndrome was seen among children of young mothers during 1985–1986. Three alternative explanations were considered: a first representing a maternal age specific effect, a second based on a general increase in a subgroup of cases caused by factors not related to maternal age, and a third based on the assumption that a particular birth cohort of young women was carrying a high risk. As 1987 and 1988 showed very low proportions in all age groups, the last explanation was considered less likely. Statistical modeling was used to explore which of the two remaining explanations of the temporary increase was the more likely. The observed changes were compatible with a change in the occurrence of a group of maternal age‐independent Down syndrome cases, from 4.59 per 10,000 in 1973–1984 and again in 1987–1988 to a temporary high of 7.68 per 10,000 in 1985–1986. However, the possibility of an age specific change only among young mothers could not b

ISSN:0741-0395    

DOI:10.1002/gepi.1370080403

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

年代:1991

数据来源: WILEY

摘要:

AbstractThis brief note examines the precision of segregation parameter estimates from both twin‐nuclear family and conventional nuclear family designs. The program MENDEL was used to derive expected frequencies of different family patterns of affectation (with fixed sibship size) under various single gene models, and then to estimate the standard errors (and information) associated with gene frequency and penetrance values at given sample sizes. As might be expected, a 2‐ to 5‐fold increase in relative efficiency was found for the same family size if families included an MZ twin pair among their offspring. The methods used allow convenient calculation of expected informativeness of a given study d

ISSN:0741-0395    

DOI:10.1002/gepi.1370080404

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

年代:1991

数据来源: WILEY

摘要:

AbstractAlthough the structural gene for human dopamine‐β‐hydroxylase (DBH) has been cloned, the mechanism by which DBH physical properties and activity are regulated is not well understood. Previous reports have suggested that three‐allele or two‐locus models may account for the genetic regulation of these traits in human blood. It is an interesting challenge to determine the extent to which quantitative analyses will complement or guide molecular genetic studies. In this study we analyzed data on the physical property of DBH thermal stability and DBH activity in 230 individuals in 53 families in an attempt to clarify genetic mechanisms for the inheritance of these traits. Commingling and segregation analyses of the thermal stability data provided the first clear evidence of a major gene polymorphism for DBH thermal stability analyzed as a quantitative trait. Major gene transmission was supported within a mixed model (χ [3]2= 13.39,P<.004). In keeping with earlier findings, similar analyses of DBH activity provided strong evidence of genetic transmission. However, in our data support for a major gene polymorphism was equivocal (χ (2)2

ISSN:0741-0395    

DOI:10.1002/gepi.1370080405

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe study goal was to determine the genetic (heritable) contribution to childhood brain tumors (CBT) which cause nearly one quarter of all childhood cancer deaths. Their etiology remains unknown, but previous studies have suggested a proportion of CBT may be heritable. In this study we collected family histories of 243 confirmed CBT patients referred to The University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed before age 15, and residents of the United States or Canada. Family histories were obtained for all the probands' first degree relatives (parents, siblings, and offspring) and extended to include selected second degree relatives (aunts, uncles, grandparents) using sequential sampling. To determine if these CBT families exhibited excess cancer, we compared their cancer experience to age‐, race‐, sex‐, and calendar‐year specific rates from the Connecticut Tumor Registry. No cancer excess was observed among 1,099 first and second degree relatives [39 cancers observed (O) and 44 expected (E) for a standardized incidence ratio (SIR) of 0.88]. For colon cancer, although small numbers, five cases were observed among the probands' first degree relatives with 1.6 expected, for a significant SIR of 3.10. Segregation analysis demonstrated that chance alone could not account for the observed cancer distribution with a multifactorial model providing the best overall explanation of the data. Overall, heredity played a role in the etiology of CBT in 4% of the study families: four (1.7%) due to known hereditary syndromes (nevoid basal cell carcinoma syndrome and von Recklinghausens neurofibromatosis—NF‐1), four (1.7%) with multifactorial inheritance, and two additional families with cancers aggregating similar to the clinical criteria described for the Li–Fraumeni cancer fa

ISSN:0741-0395    

DOI:10.1002/gepi.1370080406

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

年代:1991

数据来源: WILEY

摘要:

AbstractA common heritable phenotype has recently been identified which is characterized by a relative abundance of small, dense low‐density lipoproteins (LDL), and mild elevations of plasma triglycerides and reductions in plasma high‐density lipoproteins (HDL) cholesterol. This phenotype, designated LDL subclass phenotype B, has been associated with up to a three‐fold increase in coronary disease risk. Complex segregation analysis in two large family studies has demonstrated that LDL subclass phenotype B is influenced by an allele at a single genetic locus with a population frequency of 0.25–0.3, and autosomal dominant inheritance, but with full penetrance only in males age 20 and over and in postmenopausal women. Since apolipoprotein B (apoB) is the principal protein component of LDL, linkage analysis was used to investigate possible linkage between the phenotyope B phenotype and the apoB gene, using a variable number of tandem repeats site located 0.5 kb from the 3′ end of the apoB gene. In 6 informative families including only family members in the penetrant classes, a total LOD score of −7.49 was found at a recombination fraction of 0.001. Thus, under the assumptions of the single gene model, it is unlikely that the apoB locus controls LDL subclass

ISSN:0741-0395    

DOI:10.1002/gepi.1370080407

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe purpose of this commentary is to provide a framework for using the well‐known sib‐pair methodology in the context of epidemiologic study designs. Using examples from the Pittsburgh family studies of insulin‐dependent diabetes mellitus, we illustrate that the sib‐pair method can be used in family‐based epidemiologic studies. In a cohort study, unaffected relatives of probands ascertained from well‐defined populations are followed for disease development. Disease risks are indentical by descent (ibd) then stratified according to the number of alleles at one or more loci (0, 1, 2) that are identical by descent (ibd) with the proband. In the absence of linkage between the marker locus and the disease locus, disease risks are expected to be identical in the three groups. Measures of relative risk can be computed (with share‐0 as baseline group). In a case‐control study, relatives of probands that become affected (cases) are compared to a sample of relatives of probands that stay unaffected (controls) with respect to the number of alleles ibd with the proband. Measures of odds ratio can be computed (with share‐0 as baseline group). In both cohort and case‐control approaches, covariates including other genetic markers and environmental exposures can be evaluated in relation to disease risk and also for evidence of interaction with the specific marker of interest using stratified and multivariate analyses. Family‐based epidemiologic studies allow investigators to study, in a single design, the role of environmental factors and specific gene loci in the

ISSN:0741-0395    

DOI:10.1002/gepi.1370080408

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

年代:1991

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370080409

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

年代:1991

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370080401

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

年代:1991

数据来源: WILEY