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PubMed2025

The role of iPSC research for insight into inherited arrhythmia conditions.

Human induced pluripotent stem cells (iPSCs) have emerged as a transformative platform for modeling inherited cardiac arrhythmia syndromes and uncovering human-specific disease mechanisms. However, the promise of iPSC-derived cardiomyocytes lies beyond the recapitulation of arrhythmogenic phenotypes and channelopathies. In this review, we explore recent works which have enabled mechanistic interrogation and therapeutic insight for inherited arrhythmia syndromes, beyond the capabilities of traditional animal models. Such studies have leveraged iPSCs to elucidate the role of splice variants, transcriptional regulation, and mitochondrial stress in arrhythmogenesis. Further, iPSC systems have proven important for reclassifying variants of uncertain significance and in modeling idiopathic arrhythmias where genotype-phenotype links are elusive. Advances in directed differentiation now permit chamber-specific cardiac cell generation, allowing for atrial and ventricular disease modeling and revealing critical cell-cell interactions. iPSCs also serve as high-fidelity precursor platforms for drug testing, offering predictive insight into mutation-specific responses to pharmacologic and genetic therapies. Though limitations in maturation and scalability persist, ongoing efforts for integration with tissue engineering, multi-cellular models, and computational frameworks are evolving to improve model reliability. iPSC-based systems now occupy a critical role in arrhythmia research, bridging basic discovery with translational applications, thereby contributing to personalizing care and advancing therapeutics in inherited and idiopathic arrhythmic syndromes.

Humans↗
PubMed1990

Models of a dual inheritance system.

In higher plants, animals and fungi, there are two inheritance systems: the familiar system, depending on DNA sequence, used in transmitting information between sexual generations, and an epigenetic inheritance system, depending on gene activation, responsible for the transmission of states of differentiation during development. Occasionally, epigenetic changes are transmitted in sexual reproduction. A formal model of such a dual inheritance system is presented, and it is shown how the separation between the two systems can sometimes break down. The evolutionary significance of such breakdowns is discussed.

Animals↗
PubMed1996

Nuptiality and family reproduction in male-inheritance systems: reflections on the example of the Franche-Comte (seventeenth-eighteenth centuries).

"The family system practiced in the rural Franche-Comte [France] until the nineteenth century was based on egalitarian inheritance among sons and on the exclusion of daughters; as such, it was associated with distinct Malthusian nuptiality. This system cannot be understood without an examination of the formation and dynamics of a type of family that included frequent stages of undivided patrimony and coresidence in a context giving little encouragement to neolocal marriage and to the independence of sons. A comparative perspective suggests certain similarities with the stem family system, despite differences in inheritance norms.... Acceptance of the common idea of a contrast between impartible and partible inheritance should be highly qualified, insofar as partibility can hide various patterns of social reproduction. Different kinds of joint family household systems must be distinguished carefully, for they have neither the same significance nor imply the same demographic patterns."

Demography↗
PubMed2001

Evolutionary genetics. Clonal inheritance of avian mitochondrial DNA.

We have taken a new approach to test the commonly accepted, but recently questioned, principle of clonal inheritance of vertebrate mitochondrial DNA (mtDNA) by relating its inheritance to a female-specific marker of nuclear DNA. Whereas this is impossible in organisms with male heterogamy (such as mammals), we show here that genealogies of mtDNA and the female-specific W chromosome of a bird species are completely concordant. Our results indicate that inheritance of mtDNA is free of detectable recombination effects over an evolutionary timescale.

Animals↗
PubMed2002

Asymmetric inheritance of centrosomally localized mRNAs during embryonic cleavages.

During development, different cell fates are generated by cell-cell interactions or by the asymmetric distribution of patterning molecules. Asymmetric inheritance is known to occur either through directed transport along actin microfilaments into one daughter cell or through capture of determinants by a region of the cortex inherited by one daughter. Here we report a third mechanism of asymmetric inheritance in a mollusc embryo. Different messenger RNAs associate with centrosomes in different cells and are subsequently distributed asymmetrically during division. The segregated mRNAs are diffusely distributed in the cytoplasm and then localize, in a microtubule-dependent manner, to the pericentriolar matrix. During division, they dissociate from the core mitotic centrosome and move by means of actin filaments to the presumptive animal daughter cell cortex. In experimental cells with two interphase centrosomes, mRNAs accumulate on the correct centrosome, indicating that differences between centrosomes control mRNA targeting. Blocking the accumulation of mRNAs on the centrosome shows that this event is required for subsequent cortical localization. These events produce a complex pattern of mRNA localization, in which different messages distinguish groups of cells with the same birth order rank and similar developmental potentials.

Animals↗
PubMed1983

Mitochondrial inheritance in a mitochondrially mediated disease.

Mendelian inheritance involves the transmission to successive generations of DNA contained in genes in the nucleus, but DNA is also contained in mitochondria, where it is believed to be responsible for the encoding of certain mitochondrial enzymes. Since nearly all mitochondrial DNA is maternally transmitted, one might expect a nonmendelian pattern of inheritance in mitochondrial cytopathy, a syndrome in which there are abnormalities in mitochondrial structure and deficiencies in a variety of mitochondrial enzymes. We studied the pedigrees of 6 affected families whose members we had examined personally and of 24 families described in the literature. In 27 families, exclusively maternal transmission occurred; in 3 there was also paternal transmission in one generation. Altogether, 51 mothers but only 3 fathers had transmitted the condition. These results are consistent with mitochondrial transmission of mitochondrial cytopathy; the inheritance and enzyme defects of mitochondrial cytopathy can be considered in the light of recent evidence that subunits of respiratory-enzyme complexes are encoded solely by mitochondrial DNA. The occasional paternal transmission may be explained if certain enzyme subunits that are encoded by nuclear DNA are affected.

DNA, Mitochondrial↗
PubMed1982

Inheritance of DNA methylation in microinjected eggs of Xenopus laevis.

Plasmid DNA methylated at Hpa II sites was injected into eggs of Xenopus laevis. The methylated DNA replicates extrachromosomally, and the methylated state of the H pa II sites is inherited through replication. Unmethylated sites remain unmethylated in progeny molecules. To test whether replication is necessary for new methylation to occur, DNA methylated on one strand only was injected and unreplicated DNA was selected for analysis. Methylation was copied onto a previously unmethylated strand in the absence of replication but less efficiently than in its presence. These experiments show that the individual methylated site contains enough information for inheritance of the methylated state and that inheritance of methylation does not require integration of the DNA into the chromosome.

Animals↗
PubMed1985

Extrachromosomal inheritance of susceptibility to trypanosome infection in tsetse flies. I. Selection of susceptible and refractory lines of Glossina morsitans morsitans.

Differences in susceptibility to infection with Trypanosoma congolense between F1 families of Glossina morsitans morsitans indicated that susceptibility is maternally inherited in this species of tsetse fly. Twelve F1 families, six selected for susceptibility and six selected for refractoriness to infection, have been bred for up to 13 generations. The reciprocal differences demonstrated in the F1 generation persisted in these selected families over many generations, indicating that susceptibility/refractoriness to T. congolense infection is extrachromosomally inherited in G. m. morsitans. Repeated 'backcrossing' to males of the opposite strain showed that infection rates within families were independent of the contribution of the male parent. Susceptible families had a mean midgut infection rate of 76.9% and a mature (hypopharyngeal) infection rate of 47.9%. In the refractory families 88.9% of the flies failed to develop an infection, 11.1% had midgut infections and only 6.3% developed mature infections. Levels of midgut infection remained remarkably constant within families over generations, whether refractory or susceptible, while maturation rates varied between generations and between sexes. Males matured a significantly greater proportion of midgut infections than females in the susceptible families. It is suggested that the inheritance of susceptibility/refractoriness relates primarily to the establishment of midgut infections in G. m. morsitans, and that maturation of midgut infections is dependent upon environmental factors such as diet, and differences between sexes probably reflecting differences in rates of bloodmeal digestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Aux1p/Swa2p is required for cortical endoplasmic reticulum inheritance in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, the endoplasmic reticulum (ER) is found at the periphery of the cell and around the nucleus. The segregation of ER through the mother-bud neck may occur by more than one mechanism because perinuclear, but not peripheral ER, requires microtubules for this event. To identify genes whose products are required for cortical ER inheritance, we have used a Tn3-based transposon library to mutagenize cells expressing a green fluorescent protein-tagged ER marker protein (Hmg1p). This approach has revealed that AUX1/SWA2 plays a role in ER inheritance. The COOH terminus of Aux1p/Swa2p contains a J-domain that is highly related to the J-domain of auxilin, which stimulates the uncoating of clathrin-coated vesicles. Deletion of the J-domain of Aux1p/Swa2p leads to vacuole fragmentation and membrane accumulation but does not affect the migration of peripheral ER into daughter cells. These findings suggest that Aux1p/Swa2p may be a bifunctional protein with roles in membrane traffic and cortical ER inheritance. In support of this hypothesis, we find that Aux1p/Swa2p localizes to ER membranes.

ADP-Ribosylation Factor 1↗
PubMed2003

Fractional populations in multiple gene inheritance.

MOTIVATION: With complete knowledge of the human genome sequence, one of the most interesting tasks remaining is to understand the functions of individual genes and how they communicate. Using the information about genes (locus, allele, mutation rate, fitness, etc.), we attempt to explain population demographic data. This population evolution study could complement and enhance biologists' understanding about genes. RESULTS: We present a general approach to study population genetics in complex situations. In the present approach, multiple allele inheritance, multiple loci inheritance, natural selection and mutations are allowed simultaneously in order to consider a more realistic situation. A simulation program is presented so that readers can readily carry out studies with their own parameters. It is shown that the multiplicity of the loci greatly affects the demographic results of fractional population ratios. Furthermore, the study indicates that some high infant mortality rates due to congenital anomalies can be attributed to multiple loci inheritance. AVAILABILITY: The simulation program can be downloaded from http://won.hongik.ac.kr/~mhchung/index_files/yapop.htm. In order to run this program, one needs Visual Studio.NET platform, which can be downloaded from http://msdn.microsoft.com/netframework/downloads/default.asp.

Alleles↗
PubMed1977

Maternal inheritance of enzymes in the mealybug Pseudococcus obscurus (Homoptera).

In the mealybug Pseudococcus obscurus Essig (Pseudococcidae) two esterases, a tyrosinase and a mannosephosphate isomerase, exhibited an unusual type of maternal inheritance. Electromorphs (alleles) were transmitted by both parent but segregation was delayed by one generation and full sisters always had the same phenotype. Moreover, for esterase-1, in which three alleles were present, some of the females exhibited all three alleles. Several other polymorphic loci exhibited normal transmission and segregation. This mode of inheritance can be readily explained by assuming that most or all of the enzymes coded for by these loci are produced by the mycetocytes. The mycetocytes house intracellular bacteria-like symbionts and are usually formed by the fusion ofthe polar bodies and one or more cleavage nuclei. For a locus with two alleles exhibiting this type of inheritance, the expected frequencies of the three phenotypes are p3, 3pq an equation is presented for estimating the frequency of alleles from the frequencies of the phenotypes and it is shown that for three samples from wild populations there is a good agreement between the expected and observed frequencies of the phenotypes.

Alleles↗
PubMed2000

Evolutionary origin and consequences of uniparental mitochondrial inheritance.

In the great majority of sexual organisms, cytoplasmic genomes such as the mitochondrial genome are inherited (almost) exclusively through only one, usually the maternal, parent. This rule probably evolved to minimize the potential spread of selfish cytoplasmic genomic mutations through a species. Maternal inheritance creates an asymmetry between the sexes from which several evolutionary consequences follow. Because natural selection on mitochondria operates only in females, mitochondrial mutations may have more deleterious effects in males than in females. Strictly uniparental inheritance creates asexual mitochondrial lineages that are vulnerable to mutation accumulation (Muller's ratchet). There is evidence that over evolutionary time mitochondrial genomes have indeed accumulated slightly deleterious mutations. Mutation accumulation in animal mitochondrial genomes is probably slowed down mainly by two processes: a severe reduction in germline mitochondrial genome copy number at some point in the life cycle, enabling more effective elimination of mutations by natural selection, and occasional recombination between maternal and paternal mitochondrial genomes following paternal leakage.

DNA Repair↗
PubMedDate not supplied

Inheritance of seed color in Capsicum.

The mode of seed color inheritance in Capsicum was studied via an interspecific hybridization between C. pubescens Ruiz and Pav. (black seed color) and C. eximium Hunz. (yellow seed color). Black seed color was dominant over yellow seed color. The F(2) segregation pattern showed continuous variation. The generation means analysis indicated the presence of a significant effect of additive [d], dominance [h], and additive x additive [i] interaction for seed color inheritance. The estimate for a minimum number of effective factors (genes) involved in seed color inheritance was approximately 3.

Capsicum↗
PubMed1996

Keratouveitis--two families with a dominantly inherited disorder.

Herein we describe a relapsing acute keratouveitis without known aetiology. The disorder has been found in two families and shows an autosomal dominant inheritance. Acute anterior uveitis can be traced for five generations in one of these families. In the same family there is also an association to an autosomal dominantly inherited vascular disorder (Osler-Rendu-Weber disease). The anterior uveitis has an acute onset, a recurrent pattern and a mild activity. The associated keratitis is seen as a midstromal thin flat disc in the central cornea, sometimes with folds in Descemet's membrane as a sign of oedema. This causes a change in refraction and a mild reduction of the corrected visual acuity. There is a prompt response to topical steroid treatment, but the corneal changes have in one case become permanent. Clinical documentation and the mode of inheritance is presented.

Acute Disease↗
PubMed2003

Further evidence for the role of genes on chromosome 2 and chromosome 5 in the inheritance of pulmonary function.

The spirometric measurements FEV1, FVC, and the ratio FEV1/FVC are used in the diagnosis of lung function disorders. Therefore, understanding the genetics underlying these spirometric measurements will increase our knowledge of the genetics of pulmonary function. FEV1 and FVC were measured on 264 members of 26 Utah Genetic Reference pedigrees, originally collected for the Centre d'Etude du Polymorphisme Humain genetic mapping project. Using segregation analysis, we inferred major locus inheritance of the FEV1/FVC ratio, although we could not distinguish between a dominant or recessive mode of inheritance. No evidence of major locus inheritance was found for either FEV1 or FVC. Suggestive evidence of linkage for the ratio FEV1/FVC was found on chromosome 2 (heterogeneity lod = 2.36, dominant model) and chromosome 5 (heterogeneity lod = 2.23, recessive model), replicating linkages from other studies. In addition, nonparametric variance component linkage analysis showed linkage of FEV1/FVC in both of these regions, providing further support to the results. No nonparametric lod scores over 1.5 were obtained for either FEV1 or FVC.

Adolescent↗
PubMed2001

Maternal inheritance of the chloroplast genome in Eucalyptus globulus and interspecific hybrids.

The utility of chloroplast DNA (cpDNA) in Eucalyptus, either as a molecular marker for genetic studies or as a potential vehicle for genetic manipulation, is based on knowledge of its mode of inheritance. Chloroplast inheritance in angiosperms can vary among and within species, and anomalous inheritance has been reported in some interspecific-hybrid combinations. In Eucalyptus, abnormalities of pollen-tube growth occur in a number of interspecific-hybrid combinations, and this might increase the likelihood of anomalous chloroplast transmission. We used a rapid PCR technique to determine chloroplast heritability in 425 progeny of Eucalyptus, comprising 194 progeny of the premier pulpwood species E. globulus and 231 interspecific hybrids between E. globulus and E. nitens (F1, F2, and backcrosses). At this sampling intensity, no pollen-mediated transmission of cpDNA was found in any of the 40 families tested. The results are discussed with reference to chloroplast engineering and the use of cpDNA as a seed-specific marker in phylogeographic studies of Eucalyptus.

Chloroplasts↗
PubMedDate not supplied

[The origin of extrachromosomal inheritance factors (plasmids) in bacteria].

Present status of the problem of origin of extra-chromosomal inheritance elements is reviewed in the light of literary data and some results obtained by the author. The role of plasmids in the ecology of bacteria, in their adaptive variability and evolution is discussed. Extra-chromosomal inheritance is regarded as a particular case of biological inheritance.

Bacteria↗
PubMed1978

Investigations on the inheritance of nemaline myopathy.

Extensive investigations on 11 patients with nemaline myopathy (six index patients, five relatives), their parents, and some healthy relatives were carried out. In one family, nemaline myopathy was inherited as an autosomal dominant trait. No linkage between the locus of nemaline myopathy and the locus of seven informative genetic markers (out of 25 investigated markers) was found. In two families an autosomal recessive inheritance could be demonstrated with certainty. In these families, both parents of each index patient had rods and an increased number of fibers with internal nuclei. In two other families, one or both parents of each index patient had an increased number of fibers with internal nuclei, also indicating the possibility of autosomal recessive inheritance in these cases. It can be concluded that there are two types of nemaline myopathy. However, these two diseases could not be separated on a clinical or histopathological basis.

Adolescent↗