Lecture 7 - Inheritance of complex traits Flashcards
(22 cards)
What occurs with Mendel and his peas?
Discovered inheritance patterns (dominant & recessive:
Heterozygote x homozygote = 3:1 inheritance patterns
Homozygote x Homozygote = 1
What are the 2 types of traits of inheritance?
- continuous trait
- categorical trait
What are continuous traits?
- Human height. Humans can be 140-230cm tall, but they could be 168cm, 168.1cm or 168.3287327cm tall
- Typically have complex inheritance with multiple genes plus environmental factors
What are categorical traits?
- single gene disorders like cystic fibrosis
- in humans, could have diabetes or does not have diabetes
- multiple genetic and environmental factors
- risk factors will exceed a threshold and exhibit the disease
- ‘Threshold trait’
- Complex inheritance
What are complex traits?
Quantitative genetics studies the inheritance of traits that show complex inheritance patterns resulting from a mix of genetic and environmental factors
- may cover continuous of categorical traits
- any biological phenomenon for which variation exists may show complex inheritance and can be studied as a complex trait.
What is the variance in complex traits?
- the amount of variation in a population can be measured by a statistical measure ‘variance’.
- the variance from the population mean could be due to genetics or environmental factors
- combination of these factors lead to ‘normal curves’ of traits in population
Equation for quantifying gene-environment interactions?
x = x(line under) + g + e
x = value for trait
x(line under) = population mean
g = deviation from mean due to genetic variation
e = deviation from mean due to environmental variation
Equation for quantifying the variances caused by the environment & genetics?
Vx = Vg + Ve
Vx = total variance
Vg = total variance caused by genetics
Ve = total variance caused by environment
By making one variation 0, the other variation can be calculated.
What is a simple model for quantitative traits?
- an individual’s phenotype can be expressed in terms of its deviation from the population mean
- for example - height - Mean + 5.6cm
- The deviation is due to the genetic variation (g) and environmental variation (e)
- experiments with clones or inbred lines can be used to separate the genetic and environmental components
- Commonly done in model organisms that permit selfing (Drosophila, mice, C. elegans, yeast, Arabidopsis)
What is Nature vs Nuture?
- broad sense heritability (H^2) - squared as variances are squared
- how much of the variation in a population is due to genetics factors, and how much is due to environmental factors
- high blood pressure (continuous variation and changes over time depending on what you are doing - also, a threshold trait)
- if it’s mostly due to environmental, suggest lifestyle changed
- if it’s mostly due to genetics, then a drug that targets the gene(s) involved might be a better approach
What are the statistics of Nature vs Nurture?
H^2 = Vg/Hx
(H^2 = broad sense heritability
Hx = heritability)
- if H^2 = 0, then all the variation is due to environmental factors (e.g. inbred lines)
- if H^2 = 1, then all the variation is due to genetic factors & Vg = Hx
In lab conditions, control experiments make genetic conditions or environmental factors as close to 0 as possible.
How do we solve complex diseases?
The trick is solving the puzzle, which factor - genetics of the environment - plays a greater role in determining risk factor.
How do we evaluate gene-environmental interactions and calculate risk?
It is very difficult to define risk patterns underlying complex diseases
- Xeroderma pigmentosum (XP) exposed to UV light
- Phenylketonuria (PKU) with phenylalanine in the diet
- emphysema & smoking
What are statistical challenges of modelling complex disease risk?
- statistical power for modelling complex diseases require large numbers of people (sample sizes) from which to estimate the prevalence of a disease in the population.
- However, many complex diseases are rare
- CASE-CONTROLLED STUDIES are used to provide gene-environment interaction analyses. Case-controlled studies compare a group of patients with a non-affected patient group to identify factors that may contribute to the disease.
- case controlled studies are less powerful than large-scale trials, but they are also less expensive.
- POOLING SAMPLE (combining patient data from multiple studies) can boost statistical power
- several consortia have formed to examine gene-environment interactions in prevalent forms of complex disease. You have to watch out for the false positives with these.
What are types of twins?
- identical twins share all their genes and their home environment
- fraternal twins also share their home environment, but only half of their genes.
- so, a greater similarity between identical twins for a particular trait compared to fraternal twins, provides evidence that genetic factors play a role.
- occasionally, there are twins who share their genes, but no environment (Separated at birth)/
e.g. more twins that are identical both have Rheumatoid Arthritis compared to fraternal twins.
What is the link between complex traits, behaviours and disease?
- monozygotic twins share the same genes, but their environments become more different as they age.
- this unique aspect of twins makes then an excellent model for understanding how genes and the environment contribute to certain traits.
- when just one twin gets a disease, researchers can look for elements in the twins’ environment that are different.
- when both twins get a disease, researchers can look for genetic elements shared among similar twin pairs.
How do identical twins become more different over their life-time?
- a higher % of disease incidence in both identical twins is the first indication of a genetic component
- a % lower than 100% in identical twins indicate that genotype alone doesn’t determine susceptibility to disease
- for twins with schizophrenia, 50% identical twins share the disease, while only about 10-15% of fraternal twins do.
- the difference is evidence for a strong genetic component in susceptibility to schizophrenia.
- However, the fact that both identical twins in a pair don’t develop the disease 100% of the time indicates that other factors are involved.
What are the environmental differences that influence the differences in twins over a lifetime?
- because identical twins develop from a single fertilized egg, they have the same genome
- so, any differences between twins are due to their environments, not genetics
- recent studies have shown that many environmentally induced differences are reflected in the epigenome
- twins get more different from one another as they age
What are DNA methylation patterns across the genome?
- Chromosome 3 pairs in each set of twins are digitally superimposed
- One twins epigenetic tags are dyed red and the other twin’s tags are dyed green
- when red and green overlap, that region shows up as yellow
- the 50-year-old twins have more epigenetic tags in different places than do 3-year-old twins.
Explain how DNA methylation is used in research
- Twins with different global epigenetic patterns also showed a distinct profile in DNA methylation signal in their metaphase chromosomes.
- these differences were located in almost all telomeres and a few selected gene-rich regions (3p21).
- DNA methylation-competitive genome hybridization results again showed that monozygotic twins who were younger, has similar lifestyles, and has spent more of their lifetimes together displayed minimal DNA methylation changes in all chromosomes.
- those who were older, had different lifestyles, and had spent less of their lives together had uneven DNA methylation events.
What technique is used to research genetics using DNA methylation in twins?
Competitive genomic hybridization
Describe Nature vs Nurture (a tangled mess of the 2)
- Not everyone loves twin studies
- Prof Wendy Johnson (psychologist)
- She investigates the relationship between genes, the environment and how they influence who we become
- the criticism - cannot separate genetics from the environment
- example - family income & intelligence
- twin studies were useful to prove that there was a genetic component to behaviour
