Unit 3: Heritability

MOOC Summaries - Introduction to Human Behavioral Genetics - heritability

Unit 3: Heritability

“Mendelian Inheritance (and Terminology)… Galtonian Inheritance (aka Quantitative Genetics)… How is Heritability Estimated?… What Heritability Is and What It Is Not… Gene-Environment Interaction… Supplemental – Multivariate Biometric Approaches…” 


  • Module A: Mendelian Inheritance (and Terminology)
  • Module B: Galtonian Inheritance (aka Quantitative Genetics)
  • Module C: How is Heritability Estimated?
  • Module D: What Heritability Is and What It Is Not
  • Module E: Gene-Environment Interaction
  • Module F: Supplemental - Multivariate Biometric Approaches

Module A: Mendelian Inheritance (and Terminology)

  • Goal of the module: build up a vocabulary.
  • Mendel developed a mathematical model that gave precise predictions of inheritance.
  • In this model, each characteristic of a pea pod (e.g. color, size etc) is governed by
    • two elements (which we now call genes);
    • with one inherited from each parent;
    • one could dominate over another.
  • Terminology:
    • Gene: the Mendelian element (see above), a functional unit of inheritance;
    • Allele: alternative forms of a gene governing a particular characteristic (e.g. yellow or green for color) – can be more than two (see example of ABO blood type);
    • Genotype: the two alleles one inherits:
      • Homozygotes: green and green, or yellow and yellow
      • Heterozygotes: green and yellow, or yellow and green
  • Genes are located on chromosomes and chromosomes are strings of DNA thread-like structures that is packaged into protein. These proteins are found in the nucleus of human cells.
  • Three ways to visualize a human chromosome:
    • Pair of chromosomes (one from the father, one from the mother) – homologous chromosomes;
    • Two identical copies of one of the chromosomes (e.g from the mother) – chromatids;
    • Ideograms – a schematic of a chromosome.
  • For each chromosome:
    • There are two arms, a short (p) and a long (q) arm
    • The two arms are joined by a constricted point called the centromere of the chromosome; both ends of the chromosomes are called telomeres;
    • Genes have a particular location and that location is its locus (plural: loci)
  • Human genome consists of:
    • 23 pairs of homologous chromosomes (one from the father, one from the mother);
    • A picture of all 23 pairs is called a karyotype;
    • First 22 pairs are the autosome i.e. the non-sex chromosomes (mostly ordered by size where chromosome 1 has more genes than 22);
    • The 23rd pair is the sex chromosome – they are either X or Y, two Xs is a female, and one X and one Y is a male.
  • Humans have a diploid genome i.e. each chromosome has two copies i.e. a pair.
  • The gametes i.e. egg cells and sperm cells are in haploid state – each have only one copy of the 23 chromosomes, and when these join together, we get the full set of 23 pairs of homologous chromosomes i.e. total of 46 chromosomes.
  • Two cell divisional processes:
    • Mitosis – genetic material is duplicated to produce two identical daughter cells i.e. diploid to diploid e.g. skin cells, blood cells continuing to divide through life;
    • Meiosis – process for producing a gamete i.e. diploid to haploid.
Chop Chop MOOCs’ summary of https://class.coursera.org/behavioralgenetics-002/lecture/view?lecture_id=49

Module B: Galtonian Inheritance (aka Quantitative Genetics)

  • Quantitative genetics is very complex so the purpose here is to provide a sufficient introduction.
  • Mendel’s studied characteristics that were very particular i.e. yellow or green; what others were studying were characteristics that were continuously distributed (quantitative) e.g. how tall or heavy someone was.
  • Many thought these were two forms of inheritance until R.A. Fisher postulated that Mendelian elements (i.e. genes) could have an effect on quantitative characteristics (i.e. phenotype).
  • Explanation of the R.A. Fisher’s mathematical calculations – gist is:
    • Each gene has two or more alleles:
      • each of these alleles has a slightly different effect on a phenotype/characteristic e.g. +0.5 cm or -0.5 cm on height;
      • different combinations of these two or more alleles are possible, and hence a range of different combined effects (e.g. +0.5 & -0.5; -0.5 & -0.5; +0.5 & +0.5).
    • At the same time, that characteristic/phenotype (e.g. height) is likely to have many contributing genes i.e. many alleles and combinations of alleles.
    • Because each gene has its own locus, there would be many contributing loci.
    • Taken together, these different alleles, in different contributing genes, across the different loci, will give a large range of different combined effects that forms a continuous distribution.
  • The combined effects is what Fisher called the Polygenic Model (Greek: poly = many, genic = genes). How many loci/genes contribute? In some cases such as schizophrenia and intelligence, it can be in the hundred or thousands.
  • Two other key assumptions:
    • Each one of these loci has a small and equal effect on the phenotype;
    • Environmental effects are likely to be more important (as there are many more opportunities for influences).
  • In short: the contribution of multiple loci can give rise to quantitative i.e. continuous (such as in height) instead of just categorical (e.g. brown or black eye color) distributions in phenotypes.
  • There is a summary index of the degree to which individuals differ on quantitative traits – the index is called the variance of a distribution.
  • Biometrics is a field that seeks to understand the origin of such differences and it tries to understand the contributions to Phenotypic Variance.
  • Phenotypic Variance = Genetic Variance + Environmental Variance
    • Heritability is the proportion of the Phenotypic Variance that is due to genetic factors;
    • Environmentality = 1 – Heritability.
  • Genetic Variance can be further broken down: Genetic Variance = Additive Genetic Effects + Non-Additive Genetic Effects.
    • Additive: Each allele’s effect does not depend on what other allele(s) it is paired with; they simply add up.
    • Non-Additive: Each allele’s effect depends on what other allele(s) it is paired with i.e. there are genetic interactions between alleles.
  • Environmental Variance can also be further broken down: Environmental Variance = Shared Environmental Effects + Non-shared Environmental Effects.
    • Shared: environmental factors siblings/twins share because they are raised together (e.g. family income, parents’ approach and/or psychopathy, neighbourhood, schools etc).
    • Non-shared: environmental factors siblings/twins do not share when they are raised together (e.g. peers, accidents, differing treatment from parents etc).
  • In the initial stages of analysing phenotypes, behavioral geneticists usually focus on ACE :
    • Additive Genetic Effects (A) ;
    • Shared Environmental Effects (C);
    • Non-shared Environmental Effects (E).
    • (incidentally, ACE was also mentioned in Unit 2’s module on MISTRA)
Chop Chop MOOCs’ summary of https://class.coursera.org/behavioralgenetics-002/lecture/view?lecture_id=3

Module C: How is Heritability Estimated?

  • There are two heritability co-efficients: Total Heritability (broad sense – h) and Additive Heritability  (narrow sense – a).
  • Why two co-efficients? There are conceptual, practical and empirical/theoretical reasons.
  • These reasons suggest it is appropriate to focus on the additive effects for many traits; at the same time, total heritability is the “single most useful measure of familiar aggregation of disease”.
  • Step-by-step example of how heritability is calculated and the Falconer Model.
  • General trends from various studies:
    • Correlations:
      • Monozygotic twins (MZ) are more similar than dizygotic twins.
      • MZ twins are not perfectly similar.
      • Correlations for physical traits are not that different from psychological traits.
    • ACE estimates:
      • Most traits show moderate to large a2  estimate (i.e. proportion of additive genetic variance);
      • Most traits show moderate eestimate (i.e. proportion of non-shared environmental variance);
      • Most traits show little cestimate (i.e. proportion of shared environmental variance);
      • ACE estimates for physical traits not that different from psychological traits.
  • Need to remember that it is very challenging to get precise estimates of heritability.
Chop Chop MOOCs’ summary of https://class.coursera.org/behavioralgenetics-002/lecture/view?lecture_id=5

Module D: What Heritability Is and What It Is Not

  • Heritability is a useful index of approximately how important genetic and environmental factors are to individual differences in phenotype.
  • It is not:
    • how fixed a biological trait is (which unfortunately is how it is sometimes interpreted);
    • an index of whether a phenotype can be changed.
  • A good example of the latter is height. Height is highly heritable but it has been increasing steadily over the last 100 years.
    • Highly heritable does not the trait is fixed or that it cannot change. That height has been increasing – the change must be from environmental factors such as better public health, control of infection, diet etc (because genomes do not change that quickly).
  • A good example of the former is reading. Here the heritability index can itself can change. The Additve Genetic variance and Shared Environmental variance changed between kindergarten and first grade in a comparative study across Australia, USA, and Sweden, reflecting the different curricula they had in the different countries.
    • The changes in the heritability of reading reflect the different environments.
  • Recap: Heritability is useful for:
    • Providing an estimate of the contributions of A, C, and E, in a particular time in a particular environment;
    • Helping us decide whether at the genome level, we are likely to identify specific genetic effects (to be covered in a late unit);
    • Comparative analysis that yields important insights (like the reading example above).
Chop Chop MOOCs’ summary of https://class.coursera.org/behavioralgenetics-002/lecture/view?lecture_id=7

Module E: Gene-Environment Interaction

  • Explanation of a study by Remy Cadoret on whether genetic factors influence the level of aggression. The findings are:
    • It depends on whether the child is raised in a nurturing protective home (then the genetic factors do not influence), or in a chaotic and dysfunctional home (then they do influence).
    • There is evidence of a Gene-Environment Interaction (GxE) i.e. the magnitude of the genetic effect depends on the environment.
  • The Cadoret study assessed family histories and not the child’s genotype i.e. the evidence was indirect.
  • With the Human Genome Project, we can now measure genotypes directly.
  • Detailed explanation of a breakthrough paper that did just this i.e. measure the specific genotype, to answer the same question as the Cadoret study. The findings are:
    • If you had the high risk genotype but did not experience a lot of stress in the environment, the genetic effect was irrelevant.
    • If you had the high risk genotype, the genetic effects mattered.
    • These findings are similar to the Cadoret study.
  • In other words, when an individual inherits a vulnerability (diathesis), whether the vulnerability manifests as pathology depends on the environmental triggers (stress).
  • This is called the Diathesis-Stress Model of psychopathology and is a form of Gene-Environment Interaction. It is fundamental to the way psychologists and psychiatrists think about psychopathology (such as depression, schizophrenia, autism etc).
  • PKU (see earlier unit) is also an example of Diathesis-Stress Model – people with PKU genotype are vulnerable to suffer intellectual disability, but it depends on how much phenylalanine is in their diet (stress); if the amounts are controlled, people will not suffer intellectual disability even if the inherited the vulnerability (diathesis).
  • Gene Environment Interaction is important  because for some genotypes, we can interevene with success; research in GxE has increased exponentially.
Chop Chop MOOCs’ summary of  https://class.coursera.org/behavioralgenetics-002/lecture/view?lecture_id=9

Module F: Supplemental – Multivariate Biometric Approaches

  • With all these twin studies and their fairly extensive findings, why bother continuing to do twin studies?
  • Some reasons:
    • Longitudinal studies;
    • Characterize the nature of environmental factors;
    • Epigentic research;
    • Understand associations among multiple phenotypes, or multiple traits:
      • Detailed example using generalized anxiety disorder and major depressive disorder.
Chop Chop MOOCs’ summary of  https://class.coursera.org/behavioralgenetics-002/lecture/view?lecture_id=145

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