摘要:

AbstractLow levels of high‐density lipoprotein cholesterol (HDL‐C) are associated with increased risk of coronary heart diesease (CHD). Therefore, assessment of the mode of inheritance of HDL‐C is of importance. HDL‐C concentrations in 3,074 nuclear families in the multiethnic Jerusalem Lipid Research Center study population were analyzed for possible involvement of major genes in determination of low levels of this trait. Complex segregation analysis under the mixed model of inheritance (major gene and multifactorial components) was performed on transformed HDL‐C concentrations after adjustment for age, sex, and environmental measures. Evidence for segregation of a recessive major gene for depressed HDL‐C, with an allele frequency of q = 0.06, in addition to multifactorial transmission (H = 0.45) was found in these families. Estimates from the mixed model were homogeneous across the different ethnic groups. When the substantial multifactorial background was excluded from the model, we found evidence for an additive (codominant) Mendelian gene (d = 0.48), which demonstrates the necessity of using the mixed model. Our previous results were inconclusive with respect to the involvement of a major gene in determination of high levels of HDL‐C. However, we tentatively postulate an uncommon recessive gene for low levels of HDL‐C in the Israeli population in addition to polygenic and environment

ISSN:0741-0395    

DOI:10.1002/gepi.1370030502

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

年代:1986

数据来源: WILEY

摘要:

AbstractFamilial aggregation of a disease is usually tested using a chi square statistic on a sample of pairs of related individuals. Standard sampling designs often produce dependent observations (multiple pairs from the same family), possibly inflating the numerical value of the statistic over the value independent observations would produce. This article presents a derivation of the chi square statistic for familial aggregation, allowing for dependency because of the inclusion of the same and related persons in multiple pairs. For intraclass aggregation, the standard chi square statistic is appropriate. For interclass aggregation, an adjustment to the standard chi square statistic is needed; the adjustment depends on the disease frequency and the intraclass aggregation within each class.

ISSN:0741-0395    

DOI:10.1002/gepi.1370030503

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

年代:1986

数据来源: WILEY

摘要:

AbstractThis report describes a study that examines the hypotheses of genetic linkage between the autosomal dominant disorder neurofibromatosis (NF) and loci on human chromosomes 4 and 19. Twelve Utah families were evaluated for evidence of possible linkage of NF to six known markers on chromosome 4 and five markers on chromosome 19. Due to previous reports suggesting tight linkage of NF to the GC locus on chromosome 4 and the C3 (linked to myotonic dystrophy) locus on chromosome 19, these two markers were of particular interest. For the Utah families the cumulative LOD score for GC was −4.81 (r̂ = 0.05). Cumulative LOD scores were −0.90 (r̂ = 0.05) and −1.01 (r̂ = 0.05) for C3 serum determinations and a C3 DNA polymorphism respectively. Linkage data is also included on all individual informative families for the GC and C3 loci to specifically address the question of heterogeneity. Linkage data is consistent with, but does not strongly support, the existence of heterogeneity implicating both the GC locus on chromosome 4 and the C3 locus on chromosome 19. A compilation of cumulative LOD scores from this and other current linkage studies produces values that in the absence of heterogeneity refute previous reports for tight linkage of NF to GC a

ISSN:0741-0395    

DOI:10.1002/gepi.1370030504

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

年代:1986

数据来源: WILEY

摘要:

AbstractSimple estimators of gene frequencies and linkage disequilibria are proposed when haplotype data are available from four parental chromosomes of a child (or fetus) for whom genetic counseling is sought for a disease condition. The method is illustrated with restriction site polymorphisms associated with sickle‐cell anemia (Hb‐βS) gene as surveyed in genetic counseling data from American blacks. The method suggested here is shown to be useful in testing for the significance of interactions of site‐specific variations of any order in the chromosomal region a

ISSN:0741-0395    

DOI:10.1002/gepi.1370030505

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe study population consists of 424 three‐generation families originally ascertained through nonsyndromic cleft lip with or without cleft palate (CL ± P) surgical probands by Carter et al [J Med Genet 19:246–261, 1982] in London, England. Carter et al proposed that the multifactorial threshold model (MF/T) could explain the data. The goal of our study was to test that hypothesis, plus alternatives, rigorously.Two approaches were used: 1) Carter et al had proposed that these data were consistent with the predictions of the MF/T as presented by Carter [Br Med Bull 25:52–57. 1969]. However, we tested those predictions using standard χ2tests and found statistically significant departures from the predictions in these families. 2) Complex segregation analysis under the mixed model was performed. Again, the MF/T model could be rejected, as could a model of a major locus alone. The best‐fitting model included both major locus and multifactorial components. When the data were analyzed in two parts based on the proband's phenotype (CL vs CL + P) there was some evidence of heterogeneity in that there was a significant proportion of sporadic cases in the families of CL probands but not in the families of CL + P probands.Our results provide no support for the MF/T model. The results from segregation analyses of CL ± P in these families were most consistent with autosomal major gene inheritance plus multifactorial con

ISSN:0741-0395    

DOI:10.1002/gepi.1370030506

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

年代:1986

数据来源: WILEY

摘要:

AbstractAn adaptation of the sib pair method is given for testing the independence of transmission of Gm and the disease, using variable X (which gives information on the phenotypic identity of a sib pair for Gm). Then the joint distribution of IBD for HLA and X for Gm among affected sib pairs was derived under different two‐locus models (multiplicative and other) in which one locus is strictly linked to HLA and the other to Gm. We also propose a test for a joint effect of HLA and Gm and whether this effect is multiplicative or no

ISSN:0741-0395    

DOI:10.1002/gepi.1370030507

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe recurrence risks for an X‐linked disease with incomplete penetrance are evaluated for a sib given that an isolated proband (male or female) is affected. The derived formulae are applied to the X‐linked form of Alport and fragile X syndro

ISSN:0741-0395    

DOI:10.1002/gepi.1370030508

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

年代:1986

数据来源: WILEY

摘要:

AbstractNumerous studies of sodium‐lithium countertransport (Na‐Li CNT) have reported higher rates in essential hypertensives versus normotensive controls. We studied the distribution and the mode of inheritance of Na‐Li CNT using a sample of 238 unrelated individuals and a sample of 245 individuals in 50 pedigrees all sampled from the population at large. The distribution of Na‐Li CNT is continuous and bimodal. Our results indicate that there is a large genetic contribution to the distribution of Na‐Li CNT. The hypothesis that the effect that causes bimodality is transmitted from generation to generation is supported by the fit to these data of a restricted transmission model with τ2= 0.749. We hypothesize that this deviation of τ2from its Mendelian expectation may be attributable to heterogeneity in the etiology of the bimodality in the Na‐Li CNT distribution in the popula

ISSN:0741-0395    

DOI:10.1002/gepi.1370030509

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

年代:1986

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370030510

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

年代:1986

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370030511

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

年代:1986

数据来源: WILEY