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At least 613 records · Page 34Linked to original sources
PubMed2003

Alloplasmic male sterile Brassica napus with Enarthrocarpus lyratus cytoplasm: introgression and molecular mapping of an E. lyratus chromosome segment carrying a fertility restoring gene.

A cytoplasmic male sterility (CMS) system for Brassica napus (2n = 38; AACC) was developed by backcross substitution of its nucleus into the cytoplasm of a wild crucifer, Enarthrocarpus lyratus. Male sterility was complete, stable, and expressed in small flowers with rudimentary anthers. Since the B. napus germplasm lines were complete or partial maintainers of male sterility, the required fertility restorer gene (Rfl) was introgressed from the cytoplasm donor species. Inheritance studies carried out on F1 and F2 populations derived from hybridizing cytoplasmic male sterile and male fertile near-isogenic (PNILs) lines of B. napus 'Westar', revealed a monogenic dominant control for fertility restoration. Bulked segregant analysis with 215 RAPD primers helped in the identification of putative primers associated with fertility restoration. Co-segregation analysis of eight such primers with Rfl gene revealed two markers, OPK 15700 and OPZ 061300, which flank the Rfl locus on either side at a distance of 8.2 and 2.5 cM, respectively. These DNA markers will be useful in marker-assisted selection for improving the commercial potential of this newly developed CMS-fertility-restorer system for hybrid seed production programs in rapeseed.

Brassica↗
PubMed1979

Possible linkage between alpha-haptoglobin (Hp) and depression spectrum disease.

Depression spectrum disease is an unipolar depressive illness in which at least one member of the family has unipolar depression and at least one other first degree relative has alcoholism and/or antisocial personality; using this definition, 14 depression spectrum disease families are studied. Assuming, among other things, that variability in age of onset is environmentally caused and lognormally distributed, segregation analysis shows that the data are compatible with the dichotomy of 'affected' versus 'not affected' being due to an autosomal dominant gene. A simple environmental hypothesis in which the transmission of the illness does not depend upon the parents' type could be rejected (p less than 0.001). Linkage analysis is performed by the method of maximum likelihood, taking the best fitting Mendelian model found in the segregation analysis. The results show virtually no evidence of linkage between depression spectrum disease and C3, but suggestive evidence (lod score = 1.03) of linkage between depression spectrum disease and alpha-haptoglobin (both these linkages were previously suggested by significant results in sib-pair analyses).

Adolescent↗
PubMed2005

The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension.

BACKGROUND: Sitosterolemia is a recessively inherited disorder in humans that is associated with premature atherosclerotic disease. Mutations in ABCG5 or ABCG8, comprising the sitosterolemia locus, STSL, are now known to cause this disease. Three in-bred strains of rats, WKY, SHR and SHRSP, are known to be sitosterolemic, hypertensive and they carry a missense 'mutation' in a conserved residue of Abcg5, Gly583Cys. Since these rat strains are also know to carry mutations at other genetic loci and the extent of phytosterolemia is only moderate, it is important to verify that the mutations in Abcg5 are causative for phytosterolemia and whether they contribute to hypertension. METHODS: To investigate whether the missense change in Abcg5 is responsible for the sitosterolemia we performed a segregation analysis in 103 F2 rats from a SHR x SD cross. Additionally, we measured tail-cuff blood pressure and measured intestinal lipid transport to identify possible mechanisms whereby this mutation causes sitosterolemia. RESULTS: Segregation analysis showed that the inheritance of the Gly583Cys mutation Abcg5 segregated with elevated plant sterols and this pattern was recessive, proving that this genetic change is responsible for the sitosterolemia in these rat strains. Tail-cuff monitoring of blood pressure in conscious animals showed no significant differences between wild-type, heterozygous and homozygous mutant F2 rats, suggesting that this alteration may not be a significant determinant of hypertension in these rats on a chow diet. CONCLUSION: This study shows that the previously identified Gly583Cys change in Abcg5 in three hypertension-susceptible rats is responsible for the sitosterolemia, but may not be a major determinant of blood pressure in these rats.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1986

Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia.

We previously reported the finding of phytosterolemia, xanthomatosis, and hyperapobetalipoproteinemia (hyperapoB) in five siblings in a large Amish pedigree ascertained through a 13-year-old boy who died suddenly from advanced coronary atherosclerosis. Here, we present further analyses of the plasma levels of the plant sterol, sitosterol, of low density (beta) lipoprotein (LDL) sterol, and of LDL B protein. Of 254 relatives and spouses of the proband, 90.5% were examined. A series of genetic models were explored using a pedigree analysis where parameters reflecting frequency, transmission, and penetrance of putative genotypes were examined simultaneously using a maximum likelihood approach. Segregation analysis of the sitosterol levels showed that the phenotype of sitosterolemia was controlled by a rare autosomal recessive gene. There was also significant familial correlation in plasma sitosterol levels that was attributed to a polygenic component under a mixed model but could also be due to shared environments such as diets. The recessive model was supported by our finding that the plasma sitosterol levels in the parents and in six children born to three of the five sitosterolemics were less than 1 mg/dl, well within the normal range. The phenotype of hyperapoB is based on an elevated level of LDL B protein in the presence of a normal LDL cholesterol level (low LDL sterol to LDL B ratio). For both LDL sterol and LDL B, a polygenic model showed a slightly greater improvement in ln likelihood than did the Mendelian single locus model when both were compared to a sporadic model. Similar results were obtained for sterol levels of high density (alpha) lipoprotein (HDL) sterol. When segregation analysis was performed using the ratio of LDL sterol to LDL B, the Mendelian single locus model gave a slightly better fit to the data than did the polygenic model. While the analyses presented here provided unequivocal evidence for the recessive phenotype of phytosterolemia, we also identified a possible single gene factor that could account for the major portion of the strong familial aggregation in the ratio of LDL sterol to LDL B, and to a lesser extent LDL B. However, there is clear evidence of familial aggregation for these traits in this pedigree beyond that due to Mendelian components.

Adolescent↗
PubMed2002

[Chromosome mapping of the S-b locus for F1 pollen sterility in cultivated rice (Oryza sativa L.) with RAPD markers].

S-b is one locus for F1 pollen sterility in cultivated rice (Oryza sativa L.), and the genotype of Taichung 65 (abridged as T65) is Sj/Sj, while its isogenic line, TISL2 is Si/Si at this locus. The results of pollen fertility analysis showed that the pollen of T65 and TISL2 were fertile, but the F1 plant from T65 x TISL2 produced only 40.6% fertile pollens, and the type of sterile pollen was stainable abortive. In F2 population from the cross T65 x TISL2 and BC1F1 population from the cross T65/TISL2/T65, the individuals could be classified into plants with normal pollens and plants with semi-sterile pollens, and the ratio of number of these two types of plants agreed well with the Mendel segregation ratio in 1:1. A total of 53 fertile F2 plants were testcrossed with T65, and all of them showed sterility F1 pollen in. These results demonstrate that the F1 pollen sterility is controlled by a single gene locus S-b, and the allelic interaction of S-bi and S-bj causes the pollen carrying S-bj allele abortive. A total of 187 RFLP markers and 500 RAPD primers were used to screen the polymorphism between T65 and TISL2; only H08-1300 and Y09-1500, two bands amplified by RAPD primer H08 and Y09 were found to be polymorphic. Purified H08-1300 and Y09-1500 were used as probe to hybridize with DNAs from T65 and TISL2, and the results indicated that H08-1300 and Y09-1500 appeared to be single copy in the T65 and TISL2 genome, then the RAPD marker were successfully converted into RFLP marker. The two markers were then used to perform segregation analysis, the results from co-segregation analysis of the genotypes of these two markers and the phenotypes of pollen fertility with F2 population indicated that the S-b was linked to H08-1300 and Y09-1500, and the genetic distances between each marker and the locus were 1.3 cM and 6.6 cM, respectively. To determine the chromosomal position of the S-b locus, H08-1300 was cloned and its two ends were partially sequenced. The homologous comparative analysis of these sequences with published rice sequences with BLAST was performed, and 540 bp of left end sequence of H08-1300 showed 86% homologous with the sequence of rice PAC clone P0033D06 (Accession No. AC079357), and 94% homologies of 101 bp at right end were also observed. Clone P0033D06 had been anchored by RFLP markers R3166 that was located on 18.8 cM position of rice chromosome 5 by Japan Rice Genome Program, which suggested that the S-b locus was mapped on chromosome 5 and tightly linked with R3166. The gene mapping result from this study suggests that using the rice genomic sequences published to determine the chromosome position of RAPD marker, as well as linked genes, would be a useful approach in tagging new genes.

Base Sequence↗
PubMed1990

Segregation and sporadic cases of Duchenne muscular dystrophy in the Henan Province, China.

In the Henan province, China, the segregation ratio of Duchenne muscular dystrophy, estimated through classical segregation analysis on 103 sibships, is p = 0.462, and the maximum likelihood proportion of sporadic cases is x = 0.264. These figures are in agreement with the results of segregation analysis on 1,800 families from different countries; also, the Henan population shows a slight segregation distortion and lacks a fraction of the sporadic cases predicted under mutation-selection equilibrium. Although not statistically significant, the downward departure of the estimated parameters from their expectations under the mendelian equilibrium hypothesis (p = 0.5; x = 0.333) confirms an anomalous segregation pattern for Duchenne muscular dystrophy. A possible role of germinal mosaicism in concealing a fraction of sporadic cases is discussed.

China↗
PubMed1984

The search for genetic homogeneity in affective disorders.

In the present study we tested the fit of the Single Major Locus (SML) hypothesis, using segregation analysis for single families of affective probands treated with lithium salts, with second degree relatives included. We tested the segregation pattern for every family with two different sets of parameters: one dominant for a group that did not relapse on lithium treatment and one recessive for a group that did. We calculated the likelihood ratios for each family. The results of this study partially confirm the importance of outcome on lithium treatment in susceptibility to affective disorders. However, application of segregation analysis suggested that there is genetic heterogeneity that cannot be completely detected when using only the simple pharmacological criterion of outcome on lithium.

Bipolar Disorder↗
PubMed1992

Analysis of segregation and expression of an identified mutation at the neurofibromatosis type 1 locus.

A previously identified complex mutation, affecting exon 28 of the neurofibromatosis type 1 gene, was employed for the analysis of the expression pattern in primary cultures of neurofibroma cells and melanocytes from a café-au-lait macule of the patient, respectively. Reverse transcription and subsequent polymerase chain reaction amplification of the segment carrying the mutation revealed that both alleles were expressed in both cell types analysed, thus excluding loss of heterozygosity in this particular instance. Segregation of the alleles of the intragenic Alu sequence length-polymorphism disclosed the paternal origin of the mutated allele. Detection of this mutation was also used for presymptomatic direct DNA diagnosis in the younger child of the patient.

Adult↗
PubMed2003

A novel locus for clubroot resistance in Brassica rapa and its linkage markers.

An inbred turnip ( Brassica rapa syn. campestris) line, N-WMR-3, which carries the trait of clubroot resistance (CR) from a European turnip, Milan White, was crossed with a clubroot-susceptible doubled haploid line, A9709. A segregating F(3) population was obtained by single-seed descent of F(2) plants and used for a genetic analysis. Segregation of CR in the F(3) population suggested that CR is controlled by a major gene. Two RAPD markers, OPC11-1 and OPC11-2, were obtained as candidates of linkage markers by bulked segregant analysis. These were converted to sequence-tagged site markers, by cloning and sequencing of the polymorphic bands, and named OPC11-1S and OPC11-2S, respectively. The specific primer pairs for OPC11-1S amplified a clear dominant band, while the primer pairs for OPC11-2S resulted in co-dominant bands. Frequency distributions and statistical analyses indicate the presence of a major dominant CR gene linked to these two markers. The present marker for CR was independent of the previously found CR loci, Crr1 and Crr2. Genotypic distribution and statistical analyses did not show any evidence of CR alleles on Crr1 and Crr2 loci in N-WMR-3. The present study clearly demonstrates that B. rapa has at least three CR loci. Therefore, the new CR locus was named Crr3. The present locus may be useful in breeding CR Chinese cabbage cultivars to overcome the decay of present CR cultivars.

Brassica rapa↗
PubMed2003

Multivariate and multilocus variance components method, based on structural relationships to assess quantitative trait linkage via SEGPATH.

A general-purpose modeling framework for performing path and segregation analysis jointly, called SEGPATH (Province and Rao [1995] Stat. Med. 7:185-198), has been extended to cover "model-free" robust, variance-components linkage analysis, based on identity-by-descent (IBD) sharing. These extended models can be used to analyze linkage to a single marker or to perform multipoint linkage analysis, with a single phenotype or multivariate vector of phenotypes, in pedigrees. Within a single, consistent approach, SEGPATH models can perform segregation analysis, path analysis, linkage analysis, or combinations thereof. SEGPATH models can incorporate environmental or other measured covariate fixed effects (including measured genotypes), genotype-specific covariate effects, population heterogeneity models, repeated-measures models, longitudinal models, autoregressive models, developmental models, gene-by-environment interaction models, etc., with or without linkage components. The data analyzed can have any missing value structure (assumed missing at random), with entire individuals missing, or missing on one or more measurements. Corrections for ascertainment can be made on a vector of phenotypes and/or other measures. Because of the flexibility of the class of models, the SEGPATH approach can also be used in nongenetic applications where there is a hierarchical structure, such as longitudinal, repeated-measures, time series, or nested models. A variety of specific models are provided, as well as some comparisons with other linkage analysis models. Particular applications demonstrate the importance of correctly accounting for the extraneous sources of familial resemblance, as can be done easily with these SEGPATH models, so as to give added power to detect linkage as well as to protect against spuriously inferring linkage.

Genetic Linkage↗
PubMed2004

Naxos disease in an Arab family is not caused by the Pk2157del2 mutation. Evidence for exclusion of the plakoglobin gene.

OBJECTIVE: Naxos disease is a rare hereditary disorder characterized by palmoplantar keratoderma, woolly hair and cardiomyopathy. This study aims to determine whether Naxos disease in a Saudi Arab family is caused by the Pk2157del2 mutation that was identified in Greek families from Naxos Island where the disease had originally been described. METHODS: This study was undertaken at King Fahad Hospital of the University, Al-Khobar, and the Medical University of Hannover, in the spring of 2003. Naxos disease has been encountered in a 2-year-old girl and her 30-year-old aunt of a Saudi Arab family. Deoxyribonucleic acid samples of this family were analyzed by polymerase chain-reaction (PCR) amplification of the respective region of the plakoglobin gene, and direct nucleotide sequencing of the PCR-products. Segregation analysis was performed employing the newly detected IVS11+22G/A polymorphism. RESULTS: Molecular genetic analysis of the DNA sample of the child diagnosed with Naxos disease showed absence of the Pk2157del2 mutation. In addition, the segregation analysis revealed heterozygosity for IVS11+22G/A in the affected girl. CONCLUSION: Absence of the Pk2157del2 frameshift in the affected child proved that Naxos disease in this Saudi Arab family is not caused by the same mutation that was identified in the Greek families. Furthermore, heterozygosity for the IVS11+22G/A polymorphism provided evidence for exclusion of the plakoglobin gene in this consanguineous family.

Adult↗
PubMed2003

[Studies on genetic model in familial type 2 diabetes mellitus].

This study is to explore the genetic model of type 2 diabetes mellitus (type 2 DM) among the hereditary family. One hundred and thirty-six pedigrees of familial type 2 DM were studied. The heritability of type 2 DM was estimated according to Falconer's method and the multi-factorial inheritance analyzed according to Penrose's method. Complex segregation analysis was performed using S.A.G.E-REGD. The heritability of familial type 2 DM was 94 07%-/+5.84%. Dominant major gene might influence the genesis of type 2 DM. Analysis of multi-factorial inheritance indicated that there be two genetic patterns respectively in male and female populations. By complex segregation analysis,environment,non-transmitted and co-dominant inheritance were rejected. Autosomal dominant (AD) inheritance and autosomal recessive (AR) inheritance was accepted but AR inheritance was the best pattern. This study suggested that type 2 DM had significant heritability and genetic heterogeneity,which appeared to be a disease of multi-factorial inheritance generally and autosomal dominant (AD) inheritance in part of pedigrees.

English Abstract↗
PubMed2000

Genetic variability in milking speed of dairy goats.

The present investigation deals with the genetic variability of milking speed, measured as the volume of milk collected during the first minute of milking (MD1), and its association with dairy traits. Data originated from 2589 lactations of 1421 Alpine goats, sired by 93 bucks, measured between 1985 and 1997 at the Moissac Goat Experimental Station (Lozère, France). Two genetic analyses were carried out. Firstly, a polygenic model was used to estimate genetic and phenotypic parameters among milking speed and dairy traits using a multiple-trait animal model. Secondly, segregation analysis was used to test the hypothesis of mixed model inheritance (polygenes + major gene) for MF1. Heritability and repeatability of MF1 under the polygenic model were high (0.65 and 0.82, respectively). Estimated genetic and phenotypic correlations between milking speed and dairy traits were low, positive for yields and negative for contents. Segregation analysis yielded a highly significant likelihood ratio, confirming the segregation of a major gene with two alleles with partial dominance. The difference between the mean values of the two homozygotes was around 2.3 phenotypic standard deviation units of the trait. The major gene explained more than 60% of the estimated total genetic variance. The estimate of the 'residual' heritability, after taking into account the effect of the major locus, was 0.30.

Animals↗
PubMed2004

A three base pair deletion encoding the amino acid (lysine-270) in the alpha-cone transducin gene.

PURPOSE: Cone transducin plays an important role in interacting with the cone photoreceptor visual pigments and activating the cGMP-dependent phosphodiesterase. The human gene for the alpha-subunit of cone transducin (GNAT2) has been cloned and characterized. Recently achromatopsia has been associated with mutations in this gene. Cone and cone-rod dystrophies are a genetically heterogeneous group of photoreceptor diseases, in which mutations of a single gene may cause a variety of phenotypes. In this study we tested the hypothesis that mutations in GNAT2 cause cone-rod degeneration (CRD). METHODS: PCR-SSCP and heteroduplex analysis combined with automated sequencing was used for mutation detection in GNAT2 in 13 independent pedigrees with CRD. We used co-segregation analysis to establish or reject causation, when possible. Molecular computer modeling was utilized to examine the possible consequences of mutations onto GNAT2 protein structure. RESULTS: We found a novel 3 base-pair deletion, predicted to cause the loss of a highly conserved lysine at position 270 (K270del) in a French-Canadian CRD pedigree. We detected this deletion in a CRD proband, but also in his unaffected son, the proband's unaffected father and the proband's unaffected brother. However, we did not find this defect in 12 other CRD pedigrees, nor in 100 normal, culturally matched chromosomes. According to literature and our molecular computer modeling, the K270 plays an important role in securing the guanine ring in the nucleotide binding cleft of the molecule and in creating a salt bridge between the helical and GTPase domains of GNAT2. However, the K270del in GNAT2 does not appear to have extensive consequences to the structure and the function of the GNAT2. Apparently, there is a compensatory effect of lysine (K-271), which forms a hydrogen bond with the N1 ring nitrogen substituting for the loss of the lysine at position 270. CONCLUSIONS: We detected a deletion of a highly conserved lysine at codon 270 in a critical functional area of the alpha-cone transducin molecule. The co-segregation analysis showed that the deletion is not co-inherited with the disease phenotype and therefore is not the disease causing mutation. Apparently the function of this molecule is not altered by this mutation, due to a compensatory effect of aminoacid 271. Taken together, the presence of this deletion in healthy individuals, and our protein modeling results, predict that alpha-cone transducin molecule is able to tolerate structurally and functionally the K270del.

Adult↗
PubMed2006

Segregation ratio in cranio-cerebello-cardiac syndrome.

According to several authors cranio-cerebello-cardiac (3C) syndrome is an autosomal recessive disorder. This opinion was based on pedigree inspection without formal segregation analysis. Recently, the assumption of autosomal recessive inheritance was challenged by the observation of overlapping features with 6p deletions. We therefore performed segregation analysis by means of methods described by Li and Mantel, Davie and Lange on 27 pedigrees selected from literature. The results of all three methods are consistent with autosomal recessive inheritance but their broad confidence intervals leave room for other explanations as well. Reporting of 3C cases without evaluation of 6p copy number should be discouraged from now on.

Craniofacial Abnormalities↗
PubMed2000

Clinical and genetic analysis of a large North European Caucasian family affected by early-onset periodontitis.

Genetic studies of early-onset periodontitis (EOP) are hampered by several factors. These include delayed onset of the trait, an upper age limit of expression of the disease, and lack of phenotypic information for edentulous family members. Segregation analyses of families with EOP support a major locus hypothesis but fail to define clearly the criteria used for diagnosis of the relatives. Confirmation of a proposed mode of inheritance and the identification of risk genes is awaited by means of family linkage studies. It is suggested that a system can be developed for the current and retrospective diagnosis of relatives of EOP probands. In addition, it is hypothesized that the large family presented here is suitable for a linkage study. Relatives of the proband who were unavailable for a full periodontal examination, were edentulous, or were deceased, were diagnosed by means of documented clinical evidence of periodontal disease or from reported case histories. Segregation analysis was performed. Analysis of the power of the pedigree to detect linkage was carried out by means of the SIMLINK program. Three different categories were defined according to the reliability of diagnosis of EOP. Segregation analysis indicated either autosomal-dominant or X-linked-dominant inheritance in this family. The simulations showed lod scores above 3.0 for all locations of the disease gene, and for each category of diagnosis. In conclusion, a method has been developed which can be used for the diagnosis of relatives of EOP probands when ideal clinical data are unavailable. The simulations suggest that this family is suitable for a genetic linkage study with the aim of identifying the location of one or more susceptibility genes.

Adult↗
PubMed2003

A regressive model analysis of congenital sensorineural deafness in German Dalmatian dogs.

The objective of the present study was to analyze the mode of inheritance for congenital sensorineural deafness (CSD) in German Dalmatian dogs by consideration of association between phenotypic breed characteristics and CSD. Segregation analysis with regressive logistic models was employed to test for different mechanisms of genetic transmission. Data were obtained from all three Dalmatian kennel clubs associated with the German Association for Dog Breeding and Husbandry (VDH). CSD was tested by veterinary practitioners using standardized protocols for Brainstem Auditory-Evoked Response (BAER). The sample included 1899 Dalmatian dogs from 354 litters in 169 different kennels. BAER testing results were from the years 1986 to 1999. Pedigree information was available for up to seven generations. The segregation analysis showed that a mixed monogenic-polygenic model including eye color as covariate among all other tested models best explained the segregation of affected animals in the pedigrees. The recessive major gene segregated in dogs with blue and brown eye color as well as in dogs with and without pigmented coat patches. Models which took into account the occurrence of patches, percentage of puppies tested per litter, or inbreeding coefficient gave no better adjustment to the most general (saturated) model. A procedure for the simultaneous prediction of breeding values and the estimation of genotype probabilities for CSD is expected to improve breeding programs significantly.

Animals↗
PubMed2005

[Pedigree study of pathological myopia].

90 pedigrees including 1822 individuals were investigated and analyzed to find out the genetic mode of pathological myopia in Chinese population. 169 screened nuclear pedigrees from the total were divided into two groups according to mating mode, Affected * Normal or Normal * Normal. Simple segregation analysis on A * N and N * N pedigrees was performed respectively. The results showed that A * N pedigrees fit the autosomal dominant inheritance, with segregation ratio 0.6033 and sporadic proportion 13.8%, while N * N pedigrees fit autosomal recessive inheritance, with segregation ratio 0.235245 and sporadic proportion 16.3%, although autosomal dominant inheritance could not be rejected. In complex segregation analysis,SAGE-REGD software was used to fit several genetic model, including Mendelian inheritance (major gene, dominant, recessive, codominant) and non-Mendelian inheritance (non-transmitted, environment, general), and at last all Mendelian inheritances including major gene, dominant, recessive, codominant inheritance were accepted, while codominant inheritance with minimus AIC was best fitted. Our study manifests that pathological myopia in Chinese population fits autosomal dominant and autosomal recessive inheritance with certain sporadic proportion, which demonstrates the high genetic heterogeneity of pathological myopia.

Chromosome Segregation↗