MCG - Introduction to Genetic Variation Flashcards
What are polymorphisms?
DNA differs between humans by 0.1% or 1 in 1000bp.
These differences are called polymorphisms.
Polymorphisms are usually considered to be:
- neutral variations in the DNA sequence
- common in the general population (freq >1%)
Describe Single Nucleotide Polymorphisms (SNPs).
They are single base substitutions that occur across the genome. They are the most abundant type of polymorphism in the human genome.
They can occur in coding exons, often without any detrimental effects. They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome.
Some are associated with phenotypic differences while others are not.
They generally have 2 alleles (bi-allelic)
Define ‘haplotype’.
A series of SNP alleles along a single chromosome.
Define ‘genotypes’.
Two alleles present at a SNP in an individual.
Define ‘alleles’.
Different versions of the same variant.
What does it mean when two SNPs are in linkage disequilibrium?
SNPs in the same genetic region may be correlated.
Lets say that SNP1 and SNP 2 are in linkage disequilibrium. Knowing the allele at SNP 1 gives you information on the allele at SNP2.
Describe tandem repeat polymorphisms.
Much of non-coding DNA is repetitive i.e. consists of DNA sequences that occur over and over again, e.g. repeats of ATTCC.
Repeats may be polymorphic, with individuals carrying different numbers of repeats.
The numbers of basepairs in a repeat can be from two basepairs upwards
Microsatellite markers are CACACACACA.
They can be used in forensic investigations for identity matching.
Describe Huntington’s disease, linked to tandem repeat polymorphisms.
There is a trinucleotide CAG triplet repeat (cytosine-adenine-guanine) in the gene coding for the Huntingtin protein.
Carrying less than 36 repeats gives no increased risk, but carrying over 40 repeats leads to Huntington’s disease.
An abnormal protein gradually damages the cells in the brain.
Describe ALS/motor neurone disease, linked to tandem repeat polymorphisms.
There are hexanucleotide repeats on chromosome 9 in the gene C9orf72. it is a repeat expansion of GGGGCC (6 base pairs long).
Most people carry ~ 30 GGGGCC repeats. However, some people carry ~100 repeats, which increases their risk of ALS.
Describe structural genetic variation.
Segments of DNA can be absent in some chromosomes or present in multiple tandem copies. These are known as copy number variant (CNV) or polymorphism (CNP).
These segments can contain 100s of genes, and may have an impact on health, increasing risk of specific diseases.
Another example of a structural variation is a chromosome inversion.
What is the Hardy-Weinberg Equilibrium?
It is used to explain the stability of allele and genotype frequencies within a population.
HWE describes a balanced relationship between genotype frequencies
and allele frequencies. Knowledge of the former allows you to predict the latter (and vice versa).
The preface of the equilibrium is that the frequencies of alleles and genotypes will remain stable across generations.
For this to remain true, these requirements must be met:
- large population
- no migration (so population closed, so no change in frequencies)
- no new mutation
- so selection
- random mating
How do we get changes in allele frequency?
All genetic variants will change in their frequency over long time periods, due to genetic drift (= random change).
Selection acts on top of random drift. It usually leads to much faster changes in allele frequencies over time. It also leads to an increase in frequency of one allele in the population due to higher fitness of some genotypes.
Fitness measures the ability of genotypes to reproduce. It is measured on a scale between zero (no reproduction) and one (full reproductive ability).
How does migration impact genetic variation?
It leads to diversity of genetic variants across the globe, and different allele frequencies between ethnic groups.
This holds implications for genomic medicine.
Our genome is constantly changing.
Explain how most new mutations have no biological effect.
Some may be incompatible with life.
Some may be lost after one generation, not transmitted to next generation.
Others may remain in the gene pool.
Nevertheless, some mutations may increase the risk of a disease, or affect a trait.
Describe quantitative genetics.
Many human traits have a normal distribution (bell-shaped). Examples would be: height, IQ, blood pressure.
Quantitative characters are usually determined by genes and by the environment.
Quantitative genes have additive, approximately equal and small effect on the phenotype (polygenic).
