lecture 6 - genomic and genetic variation Flashcards
What are complex traits?
The traits that Mendel studied were single-gene traits
Each one was determined by variation at a single gene and the traits are for the most part not influenced by the environment
However, complex traits are influenced by multiple genes as well as by the environment
Complex traits are much more prevalent than single gene traits
Most single-gene traits often appear in one of two or a few different phenotypes, such as round vs. wrinkled seeds. These traits are often identified by mutagenesis.
In many complex traits, the phenotype is determined by a measurement: number, size, shape, yield etc.
Complex traits like these are called quantitative traits because they are measured along a continuum with only small intervals between similar individuals.
Complex traits can also be influenced by the environment
Describe how expression of complex traits is susceptible to lifestyle choices and other environmental factors
For example:
Inadequate nutrition may slow growth and development.
Increased salt intake is associated with an increased likelihood of high blood pressure.
A poor diet high in fat and carbohydrates is a risk factor for obesity and diabetes.
Soil moisture and nutrients are needed for maximum yields in crops
These environmental effects are seen in true-breeding (homozygous) strains, also called inbred lines.
Most crops are from the genetically identical seeds, but the variation observed throughout a field is due to the environment (i.e., sunlight, water, wind, nutrients, etc.).
Explain how Mendel’s laws also apply to complex traits
Because many genes contribute to complex traits, different genotypes can have very similar phenotypes
It is difficult to see the effects of individual genes (and Mendelian ratios are not easily observed)
Where the effects of the environment are low and the number of genes is small, the basis of the trait can be analysed
It is possible to demonstrate that complex traits are subject to the same laws for single-gene traits
But that the inheritance patterns are more difficult to see because of the number of genes involved.
Explain how both genotype and environment affect complex traits
During meiotic cell division, segregation and recombination break up combinations of genes that contribute to complex traits. This means that the extreme phenotypes, such as very tall or very short, that are present in the parents are less likely to be present in the progeny even if both parents show the same extreme phenotype. The combinations of genes in the progress is likely to be different
The phenotype of the parents results not only from genes, but also from the environment. Environmental effects are not inherited and the same phenotypes will not necessarily appear in the offspring
Describe twin studies on heritability
Galton also pioneered studies of twins as a way to separate the effects of genotype and environment in phenotype differences among individuals.
Identical twins arise from a single fertilised egg, which, after several rounds of cell division, separate into two distinct but genetically identical embryos.
(Non-identical, or fraternal twins, result when two separate eggs, produced by double ovulation, are fertilised by two different sperm, making them only as closely related as any other pair of siblings)
Identical twins share the same genotype, it is likely that differences between them are due to their environment. Twin studies are difficult to carry out because the environment between identical twins is quite often identical itself.
Ongoing studies from the University of Minnesota begun about 30 years ago uniting twins separated at birth found astonishing coincidences.
Concordance is defined as the percentage of cases in which both members of a pair of twins show the trait when it is known that at least one member shows it
High concordance rates suggest that the disorders have an important genetic component. Since none of them have a 100% concordance rate, this indicates that both genes and the environment play a role in the differences observed
Describe how multiple genetic and environmental factors affecting complex traits imply that different people can have the same disease for different reasons
Examples of diseases with different causes:
Breast cancer (resulting from BRCA1 or BRCA2 mutation, or other genetic or environmental factors)
Emphysema (resulting from alpha-1 antitrypsin mutation, or cigarette smoking)
High cholesterol, high blood pressure, and depression are also examples of diseases that can be the result of different underlying genetic or environmental factors.
The traditional strategy for treating diseases is to use the same medicine for everyone with the same disease, even though the same disease may have different causes.
What if we were to identify a patient’s genotype for each of the relevant genes and then match the treatment to the genetic risk factors in each patient?
Personalised medicine not only aims to identify ahead of time medicine that will work effectively, but also to avoid medicines that may lead to harmful side effects.
Examples where personalised medicine is making headway:
Asthma - differences in response to albuterol inhalation have been traced to genetic variation in the gene ADRB2
Alzheimer’s disease - some treatment drugs are less effective in women with a particular genotype for the APOE gene
High cholesterol - drug treatment can cause muscle weakness; more than half of the cases of muscle weakness can be traced to genetic variation in the SLCO1B1 gene, a liver transport protein
Explain how genetic variation can help deliver personalised medicine and better crops for different environments
Genome sequencing is now much cheaper and much faster - it is now possible to capture the genetic variation the exists in a population
The aim of the 1000 Genomes Project is to find most genetic variants that have frequencies of at least 1% in populations
When a genome is sequenced it is broken up into small fragments, which are then sequenced more-or-less randomly
To sequence a single genome accurately you would on average need to sequence a genome 28X to ensure it was all sequenced.
However, sequencing is still expensive and there are a small number of haplotypes (different sequences in a genome).
Most genome projects now aim to sequence an individual genomes 4X in attempt to sequence the whole genome.
This should identify a significance proportion of genotypes and variants.
