6.5 Inheritance Patterns

4 min read•august 22, 2024

Inheritance patterns are complex, involving multiple genes and environmental factors. Polygenic traits, like height and skin color, are influenced by many genes working together. This topic explores how these traits are inherited and measured.

Epigenetic modifications add another layer of complexity to inheritance. These reversible changes to DNA or histones can affect gene expression without altering the DNA sequence. Some epigenetic marks can even be passed down to future generations.

Inheritance of Polygenic Traits

Polygenic Traits and Their Inheritance Patterns

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  • Polygenic traits are determined by the combined effects of multiple genes, each with a small effect on the phenotype (height, skin color, intelligence)
  • The inheritance of polygenic traits follows a continuous distribution pattern resulting in a range of phenotypes that can be represented by a bell-shaped curve

Heritability and Its Measures

  • Heritability is a measure of the proportion of phenotypic variation in a population that is attributable to genetic variation
    • It ranges from 0 to 1, with higher values indicating a greater influence of genes on the trait
  • Narrow-sense heritability (h²) specifically measures the proportion of phenotypic variation due to additive genetic effects, which can be passed from parents to offspring
  • Broad-sense heritability (H²) measures the proportion of phenotypic variation due to all genetic effects, including additive, dominant, and epistatic interactions
  • Environmental factors (nutrition, education, social influences) can also contribute to the variation in polygenic traits, reducing the heritability estimate
  • The heritability of a trait can change over time or differ between populations due to changes in genetic and environmental factors

Epigenetic Modifications and Inheritance

Epigenetic Modifications and Gene Regulation

  • Epigenetic modifications are reversible chemical changes to DNA or histones that alter gene expression without changing the underlying DNA sequence
    • These modifications include DNA methylation and histone modifications (acetylation, methylation, phosphorylation)
  • DNA methylation typically occurs at cytosine residues in CpG dinucleotides and is associated with gene silencing
    • Methylation patterns are established and maintained by DNA methyltransferases (DNMTs)
  • Histone modifications alter chromatin structure and accessibility, influencing gene expression
    • Histone acetylation generally promotes gene expression, while histone deacetylation represses gene expression
  • Epigenetic modifications play a crucial role in cell differentiation and development by regulating the expression of specific genes in different cell types and at different developmental stages

Transgenerational Epigenetic Inheritance

  • Environmental factors (diet, stress, exposure to toxins) can influence epigenetic patterns, leading to changes in gene expression that may persist throughout an individual's lifetime
  • Epigenetic modifications can be inherited across generations through transgenerational epigenetic inheritance, although the mechanisms and stability of this inheritance are still being investigated
    • In some cases, epigenetic marks can escape reprogramming during gametogenesis and early embryonic development, allowing them to be passed from parents to offspring
    • Examples of transgenerational epigenetic inheritance include the Dutch Hunger Winter and the Överkalix study, which demonstrate the effects of ancestral environmental conditions on the health of subsequent generations

Quantitative Genetics for Complex Traits

Quantitative Genetics and the Infinitesimal Model

  • Quantitative genetics is the study of the inheritance of complex traits that are influenced by multiple genes and environmental factors
    • It uses statistical methods to analyze the genetic basis of phenotypic variation in populations
  • The infinitesimal model assumes that a large number of genes with small, additive effects contribute to the variation in a quantitative trait
    • This model is the basis for many quantitative genetics analyses
  • Variance components analysis partitions the total phenotypic variance (VP) into genetic variance (VG) and environmental variance (VE)
    • Genetic variance can be further divided into additive (VA), dominance (VD), and epistatic (VI) components

Methods for Estimating Heritability and Identifying Genetic Variants

  • Heritability estimates can be calculated using various methods (parent-offspring regression, twin studies, genome-wide association studies)
    • Parent-offspring regression estimates heritability by comparing the phenotypic similarity between parents and their offspring
      • The slope of the regression line represents the narrow-sense heritability (h²)
    • Twin studies compare the phenotypic similarity between monozygotic (identical) and dizygotic (fraternal) twins to estimate the relative contributions of genetic and environmental factors to trait variation
  • Genome-wide association studies (GWAS) identify genetic variants (single nucleotide polymorphisms, or SNPs) associated with complex traits by comparing the genotypes of individuals with different phenotypes across the genome
    • GWAS can identify loci that contribute to the heritability of a trait, but they often explain only a small portion of the total heritability due to the complex nature of the traits and the limited power of the studies
  • Polygenic risk scores (PRS) are calculated based on the cumulative effects of multiple SNPs associated with a trait, as identified by GWAS
    • PRS can be used to predict an individual's genetic predisposition to a complex trait or disease
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