摘要:

AbstractGenetic linkage maps are useful tools for defining the location of disease genes. Previously published maps of human chromosome 13 have been incomplete and have had ambiguities of order in the vicinity of the Wilson disease (WND) and retinoblastoma (RBl) genes. We have defined a six‐locus map of this region using a large reference pedigree from Venezuela. Our map provides landmarks which will aid in the localization of WND, in determining the extent of deletions in retinoblastoma, and in the mapping of other marker loc

ISSN:0741-0395    

DOI:10.1002/gepi.1370050602

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

年代:1988

数据来源: WILEY

摘要:

AbstractSeveral investigators have reported that relatives of lung cancer probands have a greater‐than‐normal likelihood for developing some form of cancer. To evaluate whether this familial risk is general for probands with cancer at any site or limited to lung cancer probands, we did a case‐control study in which probands having cancer affecting any body site were identified and their pedigree data were tabulated. Telephone interviews and a mailed questionnaire were used to obtain cancer histories and environmental exposures on the families of 41 lung cancer probands, 105 probands with cancer other than lung, and 127 spouse families. Cumulative tobacco exposure (P<.05), occupational hazards (P<.005), and age of the family relatives (P<.0001) were found to be statistically significant predictors of cancer risk. With consideration given for these variables, we determined that siblings of lung cancer probands were at slightly greater risk of cancer of any kind (odds ratio [OR] = 1.43, P = .06) than siblings in the control group. Much of the elevated risk was attributable to an excess of lung cancer (OR = 2.49, P = .06). Siblings of non‐lung/non‐breast cancer probands were also determined to be at increased risk of lung cancer as well (OR = 1.61, P = .06). For parents, the risk was lower, although parental information may have been unde

ISSN:0741-0395    

DOI:10.1002/gepi.1370050603

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

年代:1988

数据来源: WILEY

摘要:

AbstractA single 51‐member kindred, ascertained on the basis of a normotriglyceridemic proband with depressed high‐density lipoprotein cholesterol (HDL‐C) and myocardial infarctions at ages 40 and 42, was studied with respect to quantitative variation in HDL‐C and apolipoprotein (apo) AI and AII levels. The results of bivariate segregation analysis suggest that the etiology of depressed HDL‐C involves one or possibly two major loci: one has a pleiotropic effect on apo AI and apo AII levels and, possibly another one that affects apo AI levels. Both the major loci were characterized as having a dominant allele leading to depression of the respective trait(s). In addition, analysis of the cosegregation of HDL‐C and apo AI levels gave evidence of residual nonfamilial factors common to both traits, leading to a positive covariance between them. This could reflect the role of apo AI in the transformation of nascent HDL‐C particles into mature ones via its cofactor activity to lecithin cholesterol acyltransferase. The proposed two‐locus model represents one possible etiology for the heterogeneous disorder of hypoal‐phalipoproteinemia. This analysis of a single pedigree does not completely define the genetic mechanism, but it does illustrate a useful new

ISSN:0741-0395    

DOI:10.1002/gepi.1370050604

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

年代:1988

数据来源: WILEY

摘要:

AbstractFor Mendelian disorders, it is usually simple to classify individuals as either affected or unaffected. By contrast, for “complex” phenotypes, the diagnostic boundary of the disorder is often uncertain. This paper explores the following question: to most efficiently detect linkage in such a complex phenotype by the affected sib pair method, where should the diagnostic threshold be drawn? The model assumes that the disorder is due to a generalized two‐allele single major locus (SML) where liability in each genotype is normally distributed. Evidence for linkage between the marker and disease loci is highly dependent on the location of the threshold. The relationship between the placement of the threshold and population linkage information (PLI) is Gaussian‐like. At high thresholds, linkage efficiency (LE) (or the amount of linkage information per affected sib pair) is high but PLI is low because the number of affected sib pairs is very small. At low thresholds, the number of affected sib pairs is high, but PLI is low because LE is very low. The model is applied to published SML parameters for schizophrenia, and maximal PLI is achieved at thresholds broader than those for schizophreni

ISSN:0741-0395    

DOI:10.1002/gepi.1370050605

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

年代:1988

数据来源: WILEY

摘要:

AbstractA recent decline in consanguineous marriages in Japan should have resulted in a decrease in the incidence of autosomal recessive disorders. Theoretical estimates were made of the chronological decrease in the incidence using a formula for Hardy‐Weinberg expectation in a partially inbred population and applying appropriate consanguinity rates, taken from the literature, during the period from 1942 to 1983. Theoretically estimated also, using Nei's extended Dahlberg's formula, is a chronological decrease in the proportion of first‐cousin marriages among the parents of affected individuals.The estimated decrease in both indices during the period was substantial, and greater in disorders of low gene frequencies. The incidence of major autosomal recessive disorders was estimated to have decreased by 40 to 80% during the period. The proportion of first‐cousin marriages among the parents of affected individuals dropped from 40–70% in 1945 to 5–15% in 1983.Theoretical estimates of the magnitude of the decrease in the incidence and in the proportion of first‐cousin marriages among the parents agreed fairly well with those of observed figures in phenylketonuria and Wilso

ISSN:0741-0395    

DOI:10.1002/gepi.1370050606

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

年代:1988

数据来源: WILEY

摘要:

AbstractThis paper considers ascertainment corrections for continuous phenotypes. Two main points are considered. The first is a discussion of what ascertainment corrections can be devised to ensure asymptotically unbiased parameter estimates when the nature of the ascertainment procedure is not known. The second is an analysis of the properties of various forms of ascertainment correction possible when the nature of the ascertainment procedure is known. Some ascertainment corrections are thus shown to be valid and others invalid.

ISSN:0741-0395    

DOI:10.1002/gepi.1370050607

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

年代:1988

数据来源: WILEY

摘要:

AbstractFriedreich ataxia (FRA) is an autosomal recessive neuromuscular disorder in which nearly all affected homozygotes eventually develop significant cardiomy‐opathy and a substantial proportion also develop diabetes mellitus. Diabetes and early heart disease have been observed previously in close blood relatives of FRA patients. To test the hypothesis that FRA heterozygotes may have elevated rates of heart disease mortality and diabetes incidence, we compared the rates of these conditions in 1,191 adult blood relatives to those in 745 nonblood relative spouse controls in 27 families of FRA patients.We found no evidence for an excess of diabetes in the blood relatives. For three broad categories of circulatory disease mortality, the FRA blood relatives had significantly higher rates than the spouse controls. However, when each relative's prior probability of heterozygosity for the FRA gene was taken into account, the resulting estimates of relative risk of dying from circulatory disease for FRA heterozygotes compared to nonheterozygotes were not significantly elevated. Since the latter analysis provides the best test of the hypothesis, our data did not strongly support the hypothesis that FRA heterozygotes are at increased risk of cardiac deat

ISSN:0741-0395    

DOI:10.1002/gepi.1370050608

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

年代:1988

数据来源: WILEY

摘要:

AbstractFrequencies of all defined HLA‐A, ‐B, ‐C (‐DR) antigens were determined in 142 (59) Germans suffering from acute lymphoblastic leukemia (ALL) with differentiation of immunologically defined or age‐related subgroups of the disease. A highly significant rise of the HLA‐C locus antigen Cw7 was found in ALL patients, particularly those over the age of 11 in comparison with local German and Caucasian controls of the Ninth Int. Histocompatibility Workshop (WS). Only slight differences of HLA‐Cw7 frequencies were observed within the four immunologically defined ALL subtypes of all or age‐related patient groups. HLA‐A, ‐B, or ‐DR antigens, as well as HLA‐ABC three‐locus haplotypes were similarly distributed in patients and their local or Caucasian controls. The results indicate HLA‐linked genetic factors conferring susceptibility to ALL in adults, particularly those presentin

ISSN:0741-0395    

DOI:10.1002/gepi.1370050609

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

年代:1988

数据来源: WILEY

摘要:

AbstractA series of functional and cell surface markers associated with a significantly increased risk of rheumatic heart disease were analyzed for the contribution of genetic factors in their presence. Peripheral blood lymphocytes from nine large kindreds from the New Zealand Maori, Polynesian, and Caucasian populations were isolated, purified, and evaluated with lymphocyte surface markers (monoclonals 83S.19.23 and D8103), as well as studied for blastogenic response to a purified group A streptococcal extracellular product, blastogen A. Segregation analysis of blastogenic response and percent of cells positive for these cell surface markers was consistent with genetic control by single major genes; however, the contribution by polygenes varied by marker, indicating heterogeneity of genetic control of identification of cell surface glycoproteins and blastogenic response to streptococcal products.

ISSN:0741-0395    

DOI:10.1002/gepi.1370050610

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

年代:1988

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370050611

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

年代:1988

数据来源: WILEY