[Genetic studies of children with neural tube defects. III. Segregation-linkage analysis of neural tube defects and the HLA system].
Explore the source record for details and available documents.
Child↗
SEARCH · Search PubMed
Results for “Segregation analysis”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Analysis of segregation in polyploid yeasts of the Peterhof genetic lines.
Explore the source record for details and available documents.
Chromosome Mapping↗
[Spatial segregation of old people in West German cities].
The presented segregation analysis of the spatial segregation of the aged produces differentiated segregation data of eight large cities of the Federal Republic of Germany for the first time. The investigations confirms the hypothesis that people who are older than 65 are the mostly segregated age group of the population. There is a trend of a longitudinal rising of segregation between 1950 and 1970. The registered high concentration of old people of lower SES in renovation-needy town areas underlines an actual important problem of town-planning politics.
Adolescent↗
Mapping of the gene for Machado-Joseph disease within a 3.6-cM interval flanked by D14S291/D14S280 and D14S81, on the basis of studies of linkage and linkage disequilibrium in 24 Japanese families.
The gene locus of Machado-Joseph disease (MJD) has recently been mapped within a 29-cM subregion of 14q chromosome. We did a linkage study of 24 multigenerational MJD Japanese pedigrees, in an attempt to narrow the candidate region of this gene. Pairwise and multipoint linkage analysis, together with haplotype segregation analysis, led to the conclusion that the MJD gene is located at the 6.8-cM interval between D14S256 and D14S81 (Zmax = 24.78, multipoint linkage analysis). D14S291 and D14S280, located at the center of this interval, showed no obligate recombination with the MJD gene (Zmax = 5.93 for D14S291 and 9.99 for D14S280). A weak, but significant, linkage disequilibrium of MJD gene was noted with D14S81 (P < .05) but not with D14S291 or D14S280. These results suggest that a 3.6-cM interval flanked by D14S291/D14S280 and D14S81 is the most likely location of the MJD gene and that it is closest to D14S81.
Adult↗
Genetic susceptibility to leprosy on a Caribbean Island: linkage analysis with five markers.
Our recent segregation analysis, carried out on 27 large pedigrees from a Caribbean island (Desirade), has shown the presence of recessive major gene(s) controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Linkage analysis was performed between each of these two detected genes and each of five markers typed in the Desirade population: HLA, ABO, Rhesus, Gm and Km. No positive significant lod score was observed. However, for leprosy per se close linkage was excluded with Rhesus and Gm (and also with ABO and HLA, considering a lower value for the frequency of the gene controlling susceptibility to leprosy per se). The highest lod score, although not significant, was obtained between the gene for nonlepromatous leprosy and ABO. Our overall results, joined with previous studies and experimental data, suggest that the gene controlling susceptibility to leprosy per se and that controlling susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.
ABO Blood-Group System↗
Segregation and linkage analysis of nine Utah breast cancer pedigrees.
The analysis of nine Utah families that were ascertained for clusters of breast cancer cases is reported. Segregation analysis of an inherited susceptibility to breast cancer shows two distinct maximum likelihood solutions that have almost equal likelihood. One model indicates that most females had zero risk for breast cancer, but 10% of the female population had risks much greater than the Utah age-specific incidence rates. The other model indicates that most females have a risk defined by the Utah rates for breast cancer, but a rare dominant gene is segregating for increased susceptibility to breast cancer. Our analysis shows that linkage results under the two models are consistent in sign but not in magnitude. No evidence for linkage was found with the 14 marker loci examined. In addition to demonstrating distortion of linkage results from ignoring sporadic cases, this analysis shows the inherent difficulty of obtaining parameter estimates for segregation analysis when families are ascertained from a cluster of cases.
Breast Neoplasms↗
Genetic studies of insulin-dependent diabetes mellitus: segregation and linkage analyses.
The inclusion of HLA data in genetic studies of insulin-dependent diabetes mellitus (IDDM) has not led to conclusive segregation models for IDDM so far. As a new approach, we first applied complex segregation analysis, independently of HLA data, to two combined Danish family materials. Then the best fitting segregation model was entered into linkage analysis of a third material, including family as well as HLA data. The best solution obtained in the segregation analysis was a mixed model, including an intermediate gene, which on the penetrance scale acts as a recessive, together with a polygenic component. The linkage analysis showed an overall recombination fraction of 0.0417 with high coupling frequencies for the HLA-DR3 and HLA-DR4 alleles and the putative disease susceptibility gene. However, when the pedigrees were divided according to whether or not the proband had the heterozygous HLA-phenotype DR3/DR4, a maximum likelihood ratio test for heterogeneity was significant, with estimated recombination fractions of 0.0 and 0.0963 in HLA-DR3/DR4 pedigrees and the remaining pedigrees, respectively. In total, we found convincing evidence that two familial factors contribute to IDDM: a locus within HLA, which very well may be DR; and an unlinked mechanism which is unimportant for HLA-DR3/DR4 but simulates recombination. If confirmed, this conclusion has important implications for further genetic studies of IDDM and complex segregation analyses of family materials sampled according to criteria which include HLA data of the probands are highly needed.
Adolescent↗
The genetic analysis of distributive segregation in Drosophila melanogaster. II. Further genetic analysis of the nod locus.
In Drosophila melanogster females the segregation of nonexchange chromosomes is ensured by the distributive segregation system. The mutation noda specifically impairs distributive disjunction and induces nonexchange chromosomes to undergo nondisjunction, as well as both meiotic and mitotic chromosome loss. We report here the isolation of seven recessive X-linked mutations that are allelic to noda. As homozygotes, all of these mutations exhibit a phenotype that is similar to that exhibited by noda homozygotes. We have also used these mutations to demonstrate that nod mutations induce nonexchange chromosomes to nondisjoin at meiosis II. Our data demonstrate that the effects of noda on meiotic chromosome behavior are a general property of mutations at the nod locus. Several of these mutations exhibit identical phenotypes as homozygotes and as heterozygotes with a deficiency for the nod locus; these likely correspond to complete loss-of-function or null alleles. None of these mutations causes lethality, decreases the frequency of exchange, or impairs the disjunction of exchange chromosomes in females. Thus, either the nod locus defines a function that is specific to distributive segregation or exchange can fully compensate for the absence of the nod+ function.
Alleles↗
General purpose model and a computer program for combined segregation and path analysis (SEGPATH): automatically creating computer programs from symbolic language model specifications.
A general purpose model and a flexible computer program, called SEGPATH, have been developed to assist in the creation and implementation of a variety of genetic epidemiological models. SEGPATH is a computer program which can be used to generate programs to implement linear models for pedigree data, based upon a flexible, model-specification syntax. SEGPATH models can perform segregation analysis, path analysis, or combined segregation and path analysis using any user-specified path model and can be structured to analyze any number of multivariate phenotypes, environmental indices, and/or measured covariate fixed effects (including measured genotypes). Population heterogeneity models, repeated-measures models, longitudinal models, auto-regressive models, developmental models, and gene-by-environment interaction models can all be created under SEGPATH. Pedigree structures can be defined to be arbitrarily complex, and the data analyzed with programs generated by SEGPATH can have any missing value structure, with entire individuals missing, or missing on one or more measurements. Corrections for ascertainment can be done on a vector of phenotypes and/or other measures. Because the model specification syntax is general, SEGPATH can also be used in non-genetic applications where there is a hierarchical structure, such as longitudinal, repeated-measures, time series, or nested models. A variety of applications are demonstrated.
Genetics, Population↗
Genetic transmission of colorectal cancer: exploratory data analysis from a population based registry.
Classical segregation analysis was conducted on 605 families of probands with colorectal carcinoma ascertained through the Cancer Registry of the Province of Modena in Italy. The families were classified as 28 suspected hereditary non-polyposis colorectal cancer (HNPCC) syndromes and 577 presumed non-HNPCC. In 11 of these, both parents had colorectal carcinoma, in 130 one parent was affected, and in 436 both parents were normal. In the suspected HNPCC families, segregation was compatible with dominant transmission of susceptibility to carcinoma. In families with one parent affected, the segregation frequency was almost exactly equal to the frequency of segregation in families where both parents were normal. The model of dominant transmission of susceptibility through a major gene with greatly reduced penetrance in heterozygotes fitted the data acceptably.
Colorectal Neoplasms↗
Major gene effects in systolic and diastolic blood pressure in families receiving a health examination in Taiwan.
BACKGROUND: Genetic factors play an important role in determining blood pressure values. Strong familial aggregation and estimated heritability values around 0.4-0.6 were reported in a white population. OBJECTIVES: To investigate the genetic components and mode of inheritance of blood pressure in Taiwan. DESIGN: A cross-sectional family study based on an adult population undergoing a health examination. SETTING AND PARTICIPANTS: A total of 1313 adults and their spouses or first-degree relatives, or both, underwent a health examination in a tertiary university hospital from August 1998 to September 1999. MAIN OUTCOME MEASURES: Genetic analyses, including comingling analysis, familial correlation and complex segregation analysis, were used to detect the genetic components and the mode of inheritance of blood pressures. RESULTS: In both systolic and diastolic blood pressure, the comingling analyses demonstrated that a more than one-component distribution provided the best fit for the data. The familial correlation coefficients showed significant parent-offspring and sibling correlation. Complex segregation analyses showed major gene effects in controlling systolic and diastolic blood pressure. CONCLUSIONS: There were significant genetic components in blood pressure among Taiwanese. Further investigation of genomic loci for the control of blood pressure is indicated.
Adult↗
Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review.
Evidence to support a role for the mismatch repair genes human mutL homolog 1 (hMLH1) and human mutS homolog 2 (hMSH2) in the etiology of colorectal cancer has come from linkage analysis, segregation studies, and molecular biologic analysis. More recently, carriers of potentially pathogenic mutations in the hMLH1/hMSH2 genes have consistently been shown to be at a greatly increased risk of developing colorectal cancer compared with the general population. When considered together, the available evidence shows a strong, consistent, and biologically plausible association between mismatch repair gene mutations and colorectal cancer. The penetrance of mutations in hMLH1/hMSH2 is incomplete and is significantly higher in males (approximately 80%) than in females (approximately 40%). To date, evidence for gene-gene or gene-environment interactions is limited, although preliminary studies have revealed a number of avenues that merit exploration. Population screening for mutation carriers is not currently a feasible option, and mutation analysis remains restricted to either relatives of mutation carriers or colorectal cancer cases selected on the basis of phenotype.
Adaptor Proteins, Signal Transducing↗
Inheritance of random amplified polymorphic DNA markers in an interspecific cross in the genus Stylosanthes.
The inheritance of random amplified polymorphic DNA (RAPD) markers generated via the polymerase chain reaction amplification of genomic DNA sequences in an F2 family of an interspecific cross between Stylosanthes hamata and S. scabra was investigated. An initial comparison between the parental species, S. hamata cv. Verano and S. scabra cv. Fitzroy, demonstrated that 34% of detected RAPD bands were polymorphic. Of 90 primers tested, 35 showed relatively simple and reliably scorable polymorphisms and were used for segregation analysis. Sixty F2 individuals were scored for the segregation of 73 RAPD markers and 55 of these markers fit a 3:1 ratio. Segregation of eight other RAPD markers deviated significantly from a 3:1 ratio. There was no bias in the inheritance of RAPD markers regarding parental origin of the segregating RAPD markers. Linkage analysis revealed 10 linkage groups containing a total of 44 RAPD loci. Another 10 RAPD markers (7 of maternal origin) that were polymorphic between the parents did not segregate in the F2 population. One of the maternally inherited RAPD bands hybridized to chloroplast DNA. Analysis of RAPD loci by DNA hybridization indicated that mainly repeated sequences were amplified. These data indicate that RAPDs are useful genetic markers in Stylosanthes spp. and they may be suitable for genetic mapping.
Base Sequence↗
The genetic susceptibility to insulin-dependent diabetes mellitus: combined segregation and linkage analysis.
We report a combined segregation and linkage analysis of a Danish sample of 216 insulin-dependent diabetes mellitus (IDDM) nuclear families: of these 216, twenty multiplex families were haplotyped regarding HLA-DR and -B markers. The analysis was conducted using the computer program COMBIN, which includes a modifier to absorb family resemblance that is additional to the effect of the major locus that is assumed linked to a marker locus, eg, within the HLA region. The initial analysis could clearly reject a dominant major locus but could not discriminate between other models with or without modifier. However, after adding supplementary information on population associations between HLA and IDDM together with the identity-by-descent (IBD) distribution to the analysis, a final model was identified. This invokes an additive major locus, linked to HLA with recombination not significantly different from 0, a disease gene frequency of 0.217, plus a dominant modifier. From this model it can be predicted that about 0.15% of the general population is at 100% risk of IDDM, about 5% is at intermediate risk (approximately 10%), while the remaining population has a risk of 0. The model predicts recurrence risks compatible with empirically estimated values. Particularly strong, positive haplotype associations were found for the DR3,B8, DR3,B18, and DR4,B15 haplotypes, but detailed analyses showed that neither these particular haplotypes nor the DR3 and DR4 haplotypes in general could entirely explain the HLA-associated susceptibility. The DR2 haplotypes showed a strong negative association. The results are discussed in the light of available data on the epidemiology of IDDM in order to provide a framework for further epidemiological studies.
Diabetes Mellitus, Type 1↗
Evidence for balancing of KM, but not GM, alleles by heterotic advantage in South Amerinds.
Two KM alleles occur in 1075 South Amerinds of 14 tribes in approximately balanced and uniform frequency. However, the number of heterozygotes is 12.7% greater than expected by frequency analysis and 16.5% greater by segregation analysis. This excess is evident in children 0-4 years of age and may reflect either prenatal or early childhood selection. The frequencies of GM haplotypes were different, and quite uniformly so, in diverse tribes. Most GM heterozygotes can only be distinguished from GM 1,2,17 21 homozygotes by DNA or family relationship. No deficit of GM homozygotes was observed in 119 children in whom heterozygosis was determined by family. Thus, the KM polymorphism, like HLA, may be maintained by preferential survival of heterozygotes, but GM probably depends on another mechanism.
Adolescent↗
Heritability and major gene effects on left ventricular mass in the Chinese population: a family study.
BACKGROUND: Genetic components controlling for echocardiographically determined left ventricular (LV) mass are still unclear in the Chinese population. METHODS: We conducted a family study from the Chin-San community, Taiwan, and a total of 368 families, 1145 subjects, were recruited to undergo echocardiography to measure LV mass. Commingling analysis, familial correlation, and complex segregation analysis were applied to detect component distributions and the mode of inheritance. RESULTS: The two-component distribution model was the best-fitting model to describe the distribution of LV mass. The highest familial correlation coefficients were mother-son (0.379, P < .0001) and father-son (0.356, P < .0001). Genetic heritability (h2) of LV mass was estimated as 0.268 +/- 0.061 (P < .0001); it decreased to 0.153 +/- 0.052 (P = .0009) after systolic blood pressure adjustment. Major gene effects with polygenic components were the best-fitting model to explain the inheritance mode of LV mass. The estimated allele frequency of the gene was 0.089. CONCLUSION: There were significant familial correlations, heritability and a major gene effect on LV mass in the population-based families.
Adolescent↗
Familial high myopia: evidence of an autosomal dominant mode of inheritance and genetic heterogeneity.
High myopia, defined as a refractive error inferior to -6 diopters, often appears as a familial disease. In order to precise its genetic background, we performed a segregation analysis on 32 French families (320 subjects including 120 individuals with clinical data) containing at least one high myopic person in their genealogy. Under the assumption of a two-alleles single gene model, the autosomal dominant transmission mode showed a much greater likelihood than the autosomal recessive mode, which therefore was rejected. From the segregation model obtained, a two-point linkage analysis was made on 18 families (107 subjects), among the 32 used for the segregation analysis. Different candidate loci were tested: collagen genes including Stickler syndrome types 1 and 2, proteoglycan genes, Marfan 1 syndrome and a Marfan like disorder localised in 3p24.2-p25. No evidence of linkage was found with any of the studied markers. In addition, the absence of linkage with chromosome 18p11.31 markers, a locus linked to familial high myopia in 6 North American families and 1 family of Chinese descent, demonstrated the genetic heterogeneity of the disease.
Alleles↗
[Genetic analysis of polyauxotrophy and early mitotic progeny of Saccharomyces cerevisiae zygotes. II. Spore-forming segregants in the mitotic and meiotic progeny of polyauxotrophic clones].
This article continues the investigation of polyauxotrophic (PA) clones formed in early mitotic progeny of zygotes. Cloning and segregation analysis of PA progeny suggest an unusual state of diploid genome in these strains, which is expressed as elimination of the dominance effect of the wild allele and as suppression or conversion of either of two loci of mating type. In PA progeny, except for recombinant haploids, sporulating diploids and unstable clones were detected. The tetrad analysis of the diploids points to homozygotization for individual markers. Over-replication of diploid set of chromosomes, prior to meiosis, and replacement of the haploid nucleus (the product of meiosis) for the diploid nucleus may explain the appearance of sporulating segregants in the diploid meiotic progeny. Unstable segregants may be considered as heterokaryons with complex interaction of nuclei.
Alleles↗