Browsing by Subject "Inheritance Patterns"

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    A longitudinal study of epigenetic variation in twins.
    (Epigenetics, 2010-08-16) Wong, Chloe Chung Yi; Caspi, Avshalom; Williams, Benjamin; Craig, Ian W; Houts, Renate; Ambler, Antony; Moffitt, Terrie E; Mill, Jonathan
    DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. Alterations in DNA methylation are established contributors to inter-individual phenotypic variation and have been associated with disease susceptibility. The degree to which changes in loci-specific DNA methylation are under the influence of heritable and environmental factors is largely unknown. In this study, we quantitatively measured DNA methylation across the promoter regions of the dopamine receptor 4 gene (DRD4), the serotonin transporter gene (SLC6A4/SERT) and the X-linked monoamine oxidase A gene (MAOA) using DNA sampled at both ages 5 and 10 years in 46 MZ twin-pairs and 45 DZ twin-pairs (total n=182). Our data suggest that DNA methylation differences are apparent already in early childhood, even between genetically identical individuals, and that individual differences in methylation are not stable over time. Our longitudinal-developmental study suggests that environmental influences are important factors accounting for interindividual DNA methylation differences, and that these influences differ across the genome. The observation of dynamic changes in DNA methylation over time highlights the importance of longitudinal research designs for epigenetic research.
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    Inter-chromosomal level of genome organization and longevity-related phenotypes in humans.
    (Age (Dordr), 2013-04) Kulminski, Alexander M; Culminskaya, Irina; Yashin, Anatoli I
    Studies focusing on unraveling the genetic origin of health span in humans assume that polygenic, aging-related phenotypes are inherited through Mendelian mechanisms of inheritance of individual genes. We use the Framingham Heart Study (FHS) data to examine whether non-Mendelian mechanisms of inheritance can drive linkage of loci on non-homologous chromosomes and whether such mechanisms can be relevant to longevity-related phenotypes. We report on genome-wide inter-chromosomal linkage disequilibrium (LD) and on chromosome-wide intra-chromosomal LD and show that these are real phenomena in the FHS data. Genetic analysis of inheritance in families based on Mendelian segregation reveals that the alleles of single nucleotide polymorphisms (SNPs) in LD at loci on non-homologous chromosomes are inherited as a complex resembling haplotypes of a genetic unit. This result implies that the inter-chromosomal LD is likely caused by non-random assortment of non-homologous chromosomes during meiosis. The risk allele haplotypes can be subject to dominant-negative selection primary through the mechanisms of non-Mendelian inheritance. They can go to extinction within two human generations. The set of SNPs in inter-chromosomal LD (N=68) is nearly threefold enriched, with high significance (p=1.6 × 10(-9)), on non-synonymous coding variants (N=28) compared to the entire qualified set of the studied SNPs. Genes for the tightly linked SNPs are involved in fundamental biological processes in an organism. Survival analyses show that the revealed non-genetic linkage is associated with heritable complex phenotype of premature death. Our results suggest the presence of inter-chromosomal level of functional organization in the human genome and highlight a challenging problem of genomics of human health and aging.
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    Sex-specific incompatibility generates locus-specific rates of introgression between species.
    (Genetics, 2011-09) Fusco, Diana; Uyenoyama, Marcy K
    Disruption of interactions among ensembles of epistatic loci has been shown to contribute to reproductive isolation among various animal and plant species. Under the Bateson-Dobzhansky-Muller model, such interspecific incompatibility arises as a by-product of genetic divergence in each species, and the Orr-Turelli model indicates that the number of loci involved in incompatible interactions may "snowball" over time. We address the combined effect of multiple incompatibility loci on the rate of introgression at neutral marker loci across the genome. Our analysis extends previous work by accommodating sex specificity: differences between the sexes in the expression of incompatibility, in rates of crossing over between neutral markers and incompatibility loci, and in transmission of markers or incompatibility factors. We show that the evolutionary process at neutral markers in a genome subject to incompatibility selection is well approximated by a purely neutral process with migration rates appropriately scaled to reflect the influence of selection targeted to incompatibility factors. We confirm that in the absence of sex specificity and functional epistasis among incompatibility factors, the barrier to introgression induced by multiple incompatibility factors corresponds to the product of the barriers induced by the factors individually. A new finding is that barriers to introgression due to sex-specific incompatibility depart in general from multiplicativity. Our partitioning of variation in relative reproductive rate suggests that such departures derive from associations between sex and incompatibility and between sex and neutral markers. Concordant sex-specific incompatibility (for example, greater impairment of male hybrids or longer map lengths in females) induces lower barriers (higher rates of introgression) than expected under multiplicativity, and discordant sex-specific incompatibility induces higher barriers.