The inheritance of immunoglobulin E: Genetic linkage analysis
Deborah A. MeyersSandra J. HasstedtDavid G. MarshMark H. SkolnickMary‐Claire KingWilma Β. BiasD. Bernard AmosJohn M. Opitz
18
Citation
21
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Linkage analyses between 21 genetic markers including HLA‐A, B, and the postulated locus for determining total serum IgE levels were done to try to clarify the inheritance of total IgE levels and to map the locus. A total of 316 individuals from five Mormon kindreds were studied, and data from an additional 204 Amish individuals from 11 families were analyzed for possible HLA linkage. Segregation analyses of both data sets did not give clear definition of the mode of inheritance of total IgE levels, but purely environmental models were rejected. Linkage analyses gave significant evidence against HLA linkage with the codominant, recessive, or dominant model of inheritance for total IgE levels. No significant evidence for linkage with any of the genetic markers was obtained. Since total serum IgE levels are correlated with allergies, understanding the genetics of total IgE levels is important to understanding the genetics of allergic disease in man.Keywords:
Genetic linkage
Inheritance
Linkage (software)
A consideration of the currently established autosomal dominant linkage relationships to ophthalmologic disorders was utilized to review the principles of linkage. If cross-over does not occur, as few as 6 informative matings can be utilized to identify probable linkage, and as few as 11 informative matings can be utilized to establish linkage. The potential implications of linkage in diagnosis, prevention, and treatment of heritable disorders was discussed.
Linkage (software)
Genetic linkage
Cite
Citations (3)
The possible linkage groups JK-JGK, MNS-GC, GPT-ESD and GPT-HP have been analysed in families of middle-European origin. Linkage of JK-JGK and MNS-GC could be confirmed, the group GPT-ESD needs further data and for GPT-HP no evidence of linkage was revealed.
Linkage (software)
Genetic linkage
Cite
Citations (1)
It was shown that sz and J are closely linked and that the recombination frequency between these two genes is 7·41 ± 2·91. It was also shown that Jis not linked with markers in linkage groups land III, and that sz is not linked with a marker in linkage group II. Therefore, linkage between sz and J is a new linkage group. Since only three linkage groups have so far been established in the Syrian hamster, linkage groups I, II and III, this new linkage constitutes linkage group IV.
Linkage (software)
Genetic linkage
Cite
Citations (0)
Our goal was to determine the degree to which joint segregation and linkage analysis leads to increased efficiency for estimating the recombination fraction and to greater power for detecting linkage, compared to separate analyses. We concentrated on the quantitative phenotype Q2 and analyzed linkage with a tightly linked marker, a loosely linked marker, and eight unlinked markers, the latter chosen to evaluate false positive rates. We considered both nuclear-family and extended-pedigree data, using the 200 replicates of each provided to GAW participants. We found joint analysis to be consistently more efficient, with relative efficiencies for the tightly linked marker of 1.16 and 1.06 in extended pedigrees and nuclear families, respectively. These relative efficiencies translated into modest but consistent gains in power to detect linkage. Both methods appear to produce unbiased parameter estimates and similar false positive rates.
Linkage (software)
Genetic linkage
Pedigree chart
Recombination Fraction
Trait
Lod score
Nuclear family
Cite
Citations (7)
Nineteen further polymorphic loci were typed on the DogMap reference panel. Five new linkage groups were identified. Additionally, five markers were added to earlier defined linkage groups. Three of the new linkage groups contain markers mapped earlier to specific dog chromosomes by physical mapping. These results make a further contribution to the canine genome map and provides more linkage groups physically assigned to known chromosomes.
Linkage (software)
Genetic linkage
Lod score
Complete linkage
Genetic linkage map
Cite
Citations (6)
Our goal was to determine the degree to which joint segregation and linkage analysis leads to increased efficiency for estimating the recombination fraction and to greater power for detecting linkage, compared to separate analyses. We concentrated on the quantitative phenotype Q2 and analyzed linkage with a tightly linked marker, a loosely linked marker, and eight unlinked markers, the latter chosen to evaluate false positive rates. We considered both nuclear-family and extended-pedigree data, using the 200 replicates of each provided to GAW participants. We found joint analysis to be consistently more efficient, with relative efficiencies for the tightly linked marker of 1.16 and 1.06 in extended pedigrees and nuclear families, respectively. These relative efficiencies translated into modest but consistent gains in power to detect linkage. Both methods appear to produce unbiased parameter estimates and similar false positive rates. © 1997 Wiley-Liss, Inc
Linkage (software)
Trait
Genetic linkage
Cite
Citations (0)
Abstract This unit provides an introduction to human genetic linkage analysis for cases in which the genetic model is known (parametric or lod score linkage analysis). The LINKAGE computer package is used for computer analysis because it remains a training standard. The concepts presented for the LINKAGE programs, however, translate directly to other commonly used programs including the FASTLINK and VITESSE programs. This unit includes seven examples selected to illustrate many of the key concepts involved in performing linkage analysis. In Examples 1 through 4, a large pedigree segregating an autosomal dominant disease with reduced penetrance is studied for linkage to various markers. In Example 5, the effects of misspecification of the marker allele frequency on linkage analysis are demonstrated.
Linkage (software)
Genetic linkage
Penetrance
Complete linkage
Lod score
Genetic Analysis
Cite
Citations (0)
One of the long term goals of psychiatric research has been to identify distinct homogeneous disease entities not only from a clinical standpoint, but also from a biological, or genetic, standpoint as well. The identification of homogeneous disease entities can be facilitated with the use of genetic linkage analysis. Here we review twelve studies that present results of sib-pair and lod score linkage analyses of alcoholism and/or subclassifications of unipolar depression, and pool their results. The results reviewed here are striking in one respect. Of the ten studies that used a sib-pair method of analysis, six suggested evidence of linkage between the various unipolar affective disorders and markers in two linkage groups—the MNS–GC linkage group on chromosome 4q and the ABO-AK1-ORM linkage group on chromosome 9q. A seventh study had nominal significance levels of 0.06 and 0.07 with the GC and MNS loci, respectively. Of the eight studies that used lod score linkage analysis, four also suggested evidence of linkage (nominal p ≤ 0.05) with markers in either of these two linkage groups. Possible evidence of linkage or association to markers in either of these two linkage groups was found in seven of the nine independent sets of families involved.
Linkage (software)
Genetic linkage
Complete linkage
Lod score
Cite
Citations (12)
Evidence for significant linkage in complexly inherited disorders usually necessitates independent, replicative studies. This study investigates the implications of including in the replicative studies families already used to suggest linkage in initial linkage analysis. We generated 1,000 unlinked replicates of 100 nuclear families with a complexly inherited disease but with no linkage to the markers analyzed. We then used a standard nonparametric linkage method to analyze these data. From the original 1,000 replicates of the original data set, one set was chosen as it yielded suggestive, but falsely positive, linkage results (LOD score = 3.4). Variable numbers of randomly selected families from this positive replicate (n = 100 families) were used to replace families in replicates of the original (unlinked) data set, and linkage analysis repeated. Overlap of families from the “positive data set” did increase the LOD scores for “unlinked data sets.” While a small amount of overlap (replacement) between a positive linkage result and the replication sample is unlikely in practice to alter results, our study suggests that steps should be taken to ensure that overlap is minimized. The implications of this overlapping recruitment on replicative linkage studies are discussed. © 2001 Wiley-Liss. Inc.
Linkage (software)
Genetic linkage
Complete linkage
Replication
Replicate
Lod score
Data set
Cite
Citations (2)