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At least 1,117 records · Page 62Linked to original sources
PubMed1998

The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation.

The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

Adult↗
PubMed1996

Mitochondrial DNA inheritance in sexual crosses of Pleurotus ostreatus.

The inheritance of mitochondrial DNA (mtDNA) in sexual crosses was investigated to expand our understanding of the large genetic divergence in mtDNAs among natural populations of the higher basidiomycete Pleurotus ostreatus. Reciprocal crosses were made between compatible monokaryons with distinguishable mtDNA restriction fragment length polymorphisms (PFLPs). Almost all of the dikaryons produced by these crosses had mtDNA genotypes from one of the parental monokaryons. However, for dikaryons isolated from the junction-zone of crossed monokaryons, recombinant mitochondrial genomes commonly appeared. These results showed that P. ostreatus mtDNA can be inherited biparentally, via mtDNA recombination, as well as uniparentally. Further, it was suggested that mtDNA recombination may be an important source of variation in mitochondrial genomes among natural populations of P. ostreatus.

Crosses, Genetic↗
PubMed2003

X-linked and lineage-dependent inheritance of coping responses to stress.

Coping-or how one routinely deals with stress-is a complex behavioral trait with bearing on chronic disease and susceptibility to psychiatric disorders. This complexity is a result of not only underlying multigenic factors, but also important non-genetic ones. The defensive burying (DB) test, although originally developed as a test of anxiety, can accurately measure differences in coping strategies by assaying an animal's behavioral response to an immediate threat with ethological validity. Using offspring derived from reciprocal crosses of two inbred rat strains differing in DB behaviors, we provide convergent phenotypic and genotypic evidence that coping styles are inherited in an X-linked fashion. We find that first-generation (F(1)) males, but not females, show maternally derived coping styles, and second-generation (F(2)) females, but not males, show significant differences in coping styles when separated by grandmaternal lineage. By using a linear modeling approach to account for covariate effects (sex and lineage) in QTL analysis, we map three quantitative trait loci (QTL) on the X Chromosome (Chr) ( Coping-1, Approach-1, and Approach-2) associated with coping behaviors in the DB paradigm. Distinct loci were associated with different aspects of coping, and their effects were modulated by both the sex and lineage of the animals, demonstrating the power of the general linear modeling approach and the important interplay of allelic and non-allelic factors in the inheritance of coping behaviors.

Adaptation, Psychological↗
PubMed1998

Sex-restricted non-Mendelian inheritance of mouse chromosome 11 in the offspring of crosses between C57BL/6J and (C57BL/6J x DBA/2J)F1 mice.

We report on the observation of sex-restricted, non-Mendelian inheritance over a region of mouse Chromosome (Chr) 11, occurring in the offspring of crosses between two commonly used Mus musculus-derived inbred strains, C57BL/6J and DBA/2J. In the surviving backcross progeny of reciprocal matings between (C57BL/6J x DBA/2J)F1 hybrids and the C57BL/6J parental strain, we observed the preferential appearance of C57BL/6J alleles along a region of Chr 11. The deviation from Mendelian predictions was observed only in female offspring from both reciprocal backcrosses, and not in males from either cross. The sex-specificity of the observed non-Mendelian inheritance points to an explanation based on embryonic or neonatal lethality. Our data add to previously obtained evidence for a Chr 11 locus or loci with sex-specific and allele-specific effects on viability.

Alleles↗
PubMed2002

Characteristics of hydrocephalus expression in the LEW/Jms rat strain with inherited disease.

MATERIALS AND METHODS: The expression and severity of hydrocephalus was characterized in LEW/Jms rats with inherited hydrocephalus. RESULTS: The frequency of overt disease (lethal) was 27.7%, but varied depending on breeding line. It increased to 31.5% when rats with mild disease were included. Most breeding pairs (48/51) produced hydrocephalic offspring with significantly more males than females affected. Some adult rats were also found to have mild (nonlethal) ventricular dilatation. When bred to Fisher F344 rats, 3% of the F(1) progeny had overt hydrocephalus, indicating that the trait is not recessive. Overt hydrocephalus was 9-20% in N(2) rats (F(1) rats x LEW/Jms). The frequency of hydrocephalus and the presence of an excess of hydrocephalic males, varied depending on the direction of the cross. Mild hydrocephalus in N(2) rats was 3.1%. CONCLUSION: It is concluded that the inheritance of hydrocephalus in LEW/Jms strain is probably not mendelian recessive but may be semidominant or involve more than one gene and has a male bias indicating possible linkage to sex chromosomes.

Animals↗
PubMed2005

Familial Dandy-Walker syndrome: a case report supporting an autosomal inheritance.

INTRODUCTION: We report an isolated pedigree in which a consanguineous couple had twin sons with Dandy-Walker malformation (DWM). The mother is similarly affected with the disorder. DISCUSSION: DWM is an abnormality of the central nervous system, which leads to hydrocephalus and is associated with other abnormalities. CONCLUSION: Inheritance of the disorder remains controversial, with the majority perceived to be sporadic cases. This report suggests an autosomal inheritance.

Adult↗
PubMed2005

Renal cell carcinoma in a pediatric patient with an inherited mitochondrial mutation.

Renal cell carcinoma (RCC) is a rare pediatric renal cancer. Recent molecular genetic studies discovered a tumor-specific mutation involving translocation of a transcription factor TFE3 in a subset of pediatric RCC with distinct histopathology. We reported a case of a 2-year-old boy with RCC associated with TFE3 translocation resulting in a PRCC-TFE3 fusion gene. Interestingly, the case carried a maternally inherited mitochondrial DNA (mtDNA) alteration at the position which is usually found in MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) syndrome (A3243G). Although evidence of somatic alterations in mtDNA existed in various cancers, association between inherited mtDNA mutation and pediatric renal cancer has not been reported. Our case provided the first evidence of a co-occurrence between a germ line mutation in mtDNA and the somatic mutation of pediatric RCC. With this information, we speculated a role of mitochondria mutation in the pathogenesis of this cancer.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2005

Replication of heterochromatin: insights into mechanisms of epigenetic inheritance.

Heterochromatin is composed of tightly condensed chromatin in which the histones are deacetylated and methylated, and specific nonhistone proteins are bound. Additionally, in vertebrates and plants, the DNA within heterochromatin is methylated. As the heterochromatic state is stably inherited, replication of heterochromatin requires not only duplication of the DNA but also a reinstallment of the appropriate protein and DNA modifications. Thus replication of heterochromatin provides a framework for understanding mechanisms of epigenetic inheritance. In recent studies, roles have been identified for replication factors in reinstating heterochromatin, particularly functions for origin recognition complex, proliferating cell nuclear antigen, and chromatin-assembly factor 1 in recruiting the heterochromatin binding protein HP1, a histone methyltransferase, a DNA methyltransferase, and a chromatin remodeling complex. Potential mechanistic links between these factors are discussed. In some cells, replication of the heterochromatin is blocked, and in Drosophila this inhibition is mediated by a chromatin binding protein SuUR.

Animals↗
PubMed2025

Pedigree analysis and genetic inheritance of fatal familial insomnia (FFI) in a Portuguese multigenerational family.

Fatal familial insomnia (FFI) is a rare, autosomal dominant prion disease caused by a mutation in the PRNP gene, leading to the misfolding of the cellular prion protein (PrPC) into its pathogenic form (PrPSc). This results in neurodegeneration, particularly in the thalamus, a key region regulating sleep-wake cycles, which underlies the hallmark symptoms of FFI, including insomnia, autonomic dysfunctions, motor disturbances and cognitive decline. This study focuses on a Portuguese family with FFI, providing a detailed pedigree analysis spanning five generations and comprising 134 individuals, to elucidate inheritance patterns, disease onset, and clinical progression. The findings confirm the autosomal-dominant inheritance pattern and a strong familial clustering of the disease with age of onset in the late 50s (mean 57 years). Although 67% of affected individuals succumbing to the disease within months to 1.5 years, a notably 33% exhibited prolonged survival beyond the typical disease duration, exceeding proportions reported in the literature. Family members retrospectively reported prodromal symptoms, including generalized pain, headaches, tinnitus, pruritus, and behavioral changes, occurring up to five years before diagnosis. In several cases, reportedly, disease onset was associated with major phycological stressors (e.g., emotional stress or mourning). While the significance of these observations remains uncertain, they may provide insights into potential early features in this kindred. Further research integrating genomic sequencing, biomarkers, and longitudinal clinical assessments are needed to better understand the mechanisms underlying the heterogeneity of FFI and to explore potential therapeutic interventions.

Humans↗
PubMed2000

Recessively inherited amyotrophic lateral sclerosis: a Germany family with the D90A CuZn-SOD mutation.

Mutations of the SOD1 gene encoding the free radical scavenging enzyme copper-zinc superoxide dismutase (CuZn-SOD) occur in patients with familial amyotrophic lateral sclerosis (ALS). Recent reports have shown homozygosity for a CuZn-SOD mutation in exon 4, the D90A (Asp90A1a) mutation. Other mutations described to date show an autosomal dominant pattern of inheritance. This is the first description of autosomal recessively inherited ALS in an out-bred population in central Europe. This study confirms the earlier described characteristic phenotype reported in D90A homozygous ALS patients in Scandinavia and supports the theory of the existence of a strong modifying factor in some cases of ALS associated with mutations in the CuZn-SOD gene.

Adult↗
PubMed2005

Inherited disorders of the IL-12-IFN-gamma axis in patients with disseminated BCG infection.

Disseminated BCG infection is a rare complication of vaccination that occurs in patients with impaired immunity. In recent years, a series of inherited disorders of the IL-12-IFN-gamma axis have been described that predispose affected individuals to disseminated disease caused by BCG, environmental Mycobacteria, and non-typhoidal Salmonella. The routine immunological work-up of these patients is normal and the diagnosis requires specific investigation of the IL-12-IFN-gamma circuit. We report here the first two such patients originating from and living in Iran. The first child is two years old and suffers from complete IFN-gamma receptor 2 deficiency and disseminated BCG infection. He is currently in clinical remission thanks to prolonged multiple antibiotic therapy. The other, a 28-year-old adult, suffers from IL-12p40 deficiency and presented with disseminated BCG infection followed by recurrent episodes of systemic salmonellosis. He is now doing well. A third patient of Iranian descent, living in North America, was reported elsewhere to suffer from IL-12Rbeta1 deficiency. These three patients thus indicate that various inherited defects of the IL-12-IFN-gamma circuit can be found in Iranian people. In conclusion we recommend to consider the disorders of the IL-12-IFN-gamma circuit in all patients with severe BCG infection, disseminated environmental mycobacterial disease, or systemic non-typhoidal salmonellosis, regardless of their ethnic origin and country of residence.

Adult↗
PubMed2005

Impact of a microphallid trematode on the behaviour and survival of its isopod intermediate host: phylogenetic inheritance?

The extent to which the ability of parasites to alter host behaviour is phylogenetically inherited as opposed to independently evolved has received little attention. We investigated the impact of an undescribed species of Microphallus on the behaviour and survival of its host, the freshwater isopod Austridotea annectens, to determine if it produced effects comparable to those induced by other trematodes of this genus. There was no difference between the vertical distribution and responses to light of infected isopods and those of uninfected isopods. In contrast, we found that infected isopods were more active swimmers than uninfected isopods, and that they failed to show the evasive responses shown by uninfected isopods when exposed to a simulated predator. There was no detectable effect of Microphallus infection on isopod survival, however. Overall, our results provide no strong evidence that the behavioural manipulation shown by our Microphallus species and that displayed by the well-studied Microphallus papillorobustus are inherited from a common ancestor rather than independently derived.

Animals↗
PubMed2001

Isolation, characterization, inheritance and linkage of microsatellite DNA markers in white spruce (Picea glauca) and their usefulness in other spruce species.

Microsatellite DNA/simple-sequence-repeat (SSR) loci were identified, isolated and characterized in white spruce (Picea glauca) by screening both a non-enriched partial genomic library and a partial genomic library enriched for (AG/TC)n-containing clones. Inheritance and linkage of polymorphic SSR loci were determined in F1 progeny of four controlled crosses. We also assessed the compatibility and usefulness of the P. glauca microsatellite DNA markers in five other Picea species. Twenty-four microsatellites were identified by sequencing 32 clones selected from screens of 5,400 clones from the two libraries. The (AG/TC)n microsatellites were the most abundant in the non-enriched library. Eight microsatellite DNA loci were of the single-copy type, and six of these were polymorphic. A total of 87 alleles were detected at the six polymorphic SSR loci in 32 P. glauca individuals drawn from several populations. The number of alleles found at these six SSR loci ranged from 2 to 22, with an average of 14.5 alleles per locus, and the observed heterozygosity ranged from 0.48 to 0.91, with a mean of 0.66 per locus. Parents of the controlled crosses were polymorphic for five of the six polymorphic SSR loci. Microsatellite DNA variants at each of these five SSR loci followed a single-locus, codominant, Mendelian inheritance pattern. Joint two-locus segregation tests indicated complete linkage between PGL13 and PGL14, and no linkage between any of the remaining SSR loci. Each of the 32 P. glauca individuals examined had unique single or two-locus genotypes. With the exception of non-amplification of PGL12 in P. sitchensis, P. mariana, and P. abies and the monomorphic nature of PGL7 in P. mariana, primer pairs for all six polymorphic SSR loci successfully amplified specific fragments from genomic DNA and resolved polymorphic microsatellites of comparable sizes in P. engelmanni, P. sitchensis, P. mariana, P. rubens, and P. abies. The closely related species P. mariana and P. rubens, and P. glauca and P. sitchensiss could be distinguished by the PGL12 SSR marker. The microsatellite DNA markers developed and reported here could be used for assisting various genetics, breeding, biotechnology, tree forensics, genome mapping, conservation, restoration, and sustainable forest management programs in spruce species.

Base Sequence↗
PubMed2001

Stability and inheritance of methylation states at PstI sites in Pisum.

The nuclear genome of pea is heavily methylated and the stability of this methylation pattern is unknown. In this study we investigated the stability of DNA methylation and its contribution to restriction fragment polymorphism as judged by AFLP fragment differences. To do this the results of a conventional AFLP analysis were compared with those obtained by a related procedure performed on pre-amplified DNA which provided a 5-methylcytosine-free DNA template (SDAFLP). Genetic mapping in a recombinant inbred (RI) population showed that polymorphisms attributable to different methylation states of PstI sites were abundant, and generally appeared to be stably inherited, although occasional failures of the inheritance of methylation states have been found. Assessments of genetic diversity by AFLP and SDAFLP were in general agreement with each other and with the currently accepted phylogeny of Pisum, but within cultivated groups the number of differences appeared to be exaggerated by AFLP. The data suggest that epigenetic differences may have played a role in the domestication of pea.

5-Methylcytosine↗
PubMed2003

Lung cancer risk in germline p53 mutation carriers: association between an inherited cancer predisposition, cigarette smoking, and cancer risk.

We recently observed a significantly increased risk for lung cancer in carriers of p53 germline mutations. Because cigarette smoking is known to play an important role in increasing the risk for lung cancer in the general population, we wanted to determine the role of cigarette smoking in lung cancer risk in people with a genetic susceptibility based on a p53 germline mutation. We studied 1263 people from 97 families enrolled in a cohort study of families systematically ascertained through childhood soft-tissue sarcoma patients treated at the M.D. Anderson Cancer Center, University of Texas, between 1944 and 1975. We assessed the incidence of lung and smoking-related cancers in 33 carriers of germline p53 mutations and in 1,230 noncarriers to determine whether there was an association between an inherited cancer predisposition, cigarette smoking, and cancer risk. We analyzed the association between cigarette smoking, mutation status, and lung and other smoking-related cancers by the Kaplan-Meier method and the Cox proportional hazards model with adjustments for birth year, race, and sex. In the hazards model, we incorporated a robust variance estimation to adjust for familial correlation. We observed an increased risk of a variety of histological types of lung cancer in the carriers of the p53 germline mutation. Mutation carriers who smoked had a 3.16-fold (95% confidence interval =1.48-6.78) higher risk for lung cancer than the mutation carriers who did not smoke. Our results demonstrate that cigarette smoking significantly increases lung cancer risk in carriers of a germline p53 mutation. This finding could be useful in designing strategies for early detection and treatment of lung and smoking-related cancers in individuals with this inherited cancer predisposition.

Adult↗
PubMed2005

Dominantly inherited cutaneous small-vessel lymphocytic vasculitis maps to chromosome 6q26-q27.

Outside the context of hereditary deficiencies of complement and IgA, Mendelian inherited predisposition to small vessel lymphocytic vasculitis (SVLV) has rarely been documented. Here we report a large, multigenerational family segregating symmetrical cutaneous SVLV affecting the cheeks, thighs and hands. In all affected family members the disease presented in early infancy and there was no evidence for an association with systemic disease. Skin biopsy of lesions showed a lymphocytic vasculitis with red blood cell extravasation. Complementary studies, with extensive investigation focused on dysfunction of the immunological system were negative. The pattern of inheritance of SVLV in the family was compatible with an autosomal dominantly acting disease gene with incomplete penetrance. To localize the disease causing gene in the family a genome-wide linkage search was conducted using a high-density SNP array. Haplotype construction and analysis of recombination events permitted the minimal interval defining the disease locus to be refined to a 4.7 Mb region on chromosome 6q26-q27. The genes CCR6 and GPR31, which map to the linked region represent plausible candidates for the disease on the basis of their biological function. Extensive screening of both genes by mutational analysis failed to identify a deleterious mutation in the family.

Chromosome Mapping↗
PubMed1997

Inheritance of cleft palate in Italy. Evidence for a major autosomal recessive locus.

Although several studies have demonstrated familial aggregation of nonsyndromic cleft palate (CP), the mode of inheritance still remains uncertain. We report the results of complex segregation analysis performed in families of 357 consecutive newborns affected with nonsyndromic CP (i.e., CP not a component feature of malformation syndrome, sequence or association), and registered in the North East Italy and Emilia Romagna congenital malformation registries in the period 1981-1993. This sample, based on a large number of consecutive births, in a well-defined geographical area, with quality control to detect associated anomalies and malformation syndromes, is independent of the number of affected subjects in the family and of CP severity, fitness, and survival. We have analyzed, using the mixed model, the whole sample of nonsyndromic CP, including isolated (i.e., without other anomalies) CP (CPI) and CP associated with at least one other anomaly (CPA), for which a diagnosis of malformation syndrome was not possible. When nonsyndromic CP (including CPA) are considered in the analysis, there is no heterogeneity between CPA and CPI nor between CP including hard palate (CPH) and CP of the soft palate only (CPS). POINTER and COMDS programs cannot discriminate between alternative genetic models; only the hypothesis of non-genetic transmission is rejected. The COMDS analysis two-locus model, which indicates that a modifier locus (or loci) operates in addition to a single major locus (SML), does not show evidence of better fit than SML, polygenic, and multifactorial models. When the severity parameter (defined as CPH and CPS) is added, CPI and CPA show heterogeneity. Eventually, when the analysis is limited to CPI and includes information on severity, a recessive SML, with low penetrance and determining CPH, provides a significant best fit. To have defined a genetic model for CPI and provided evidence for SML inheritance suggests that genetic linkage studies could be implemented. This conclusion is in agreement with previous studies which showed a significant association between alleles of transforming growth factor alpha and CP only in humans, and that single recessive genes may play a crucial role during palatogenesis in mice as well as in Brittany spaniels. Application of the candidate genes to human CPH families could reveal whether these genes are involved.

Alleles↗
PubMed1998

Inheritance of chronic tension-type headache investigated by complex segregation analysis.

We investigated the mode of inheritance of chronic tension-type headache in 122 families. The probands were from the Copenhagen Headache Clinic, Denmark. The criteria of the International Headache Society were used. The patterns of segregation of chronic tension-type headache were assessed by complex segregation analysis performed with the computer program POINTER. Of the 122 probands with chronic tension-type headache, 56 had 71 first-degree relatives with chronic tension-type headache. The complex segregation analysis indicates that chronic tension-type headache has multifactorial inheritance.

Age Factors↗