Linkage Analysis Flashcards
Define the term “Genetic Variation”
The differences in the DNA sequence’s between individuals in a population
What are the factors that cause variation?
Could either be inherited or due to environmental factors (drugs, exposure to radiation)
List the effects of Genetic Variation
- Alteration of amino acid sequence that is encoded by a gene
- Changes in gene regulation
- Physical appearance of an individual
- Silent or no apparent effect
Why is gene variation important?
- Genetic Variation underlies phenotypic differences among different individuals
- Genetic variations determine our predisposition to complex diseases and responses to drugs and environmental factors
- Genetic Variation reveals clues of ancestral human migration history
List some of the mechanisms of genetic variation
- Mutation/Polymorphism: Errors in DNA replication. This may affect single nucleotides or larger portions of DNA
- Homologous recombination: Shuffling of chromosomal segments between partner chromosomes of a pair
- Gene flow: Movement of genes from one population to another
What is the difference between a mutation and a polymorphism? (PART 1)
A mutation is a rare change in the DNA sequence that is different to the normal sequence. The ‘normal’ allele is prevalent in the population and the mutation changes this to a rare ‘abnormal’ variant
What is the difference between a mutation and a polymorphism? (PART 2)
- By contrast, a polymorphism is a DNA sequence variant that is common in the population.
- It has no single allele that is regarded as normal but instead has two or more equally acceptable alternatives
- The cut off point between a mutation and a polymorphism is a minor allele frequency
What does Meiosis and recombination produce?
- Haploid gametes
- These gametes contain a mixture of maternal and paternal material
What process occurs during homologous recombination?
- Crossing over: The reciprocal breaking and the rejoining of the homologous chromosomes during meiosis
- Results in exchange of chromosome segments and new allele combination
What is the difference between genotype and phenotype?
- Genotype is the genetic makeup of an individual
- Phenotype is the physical expression of the genetic makeup
What is the name given to genes found in alternative versions?
- Alleles
- For each characteristic, an organism inherits two alleles, one from each parent. The alleles can be the same or different
What is the difference between a homozygous and heterozygous genotype?
- A homozygous genotype has identical alleles
- A heterozygous genotype has different alleles
- A haplotype is a group of alleles that are inherited from a single parent
Describe how the chromosome looks
- The chromosome has 3 points of gene at locus.
- One at the top end and two at the lower end
- The left strand is the paternal strand
- The right strand is the Maternal strand
- The allele at the locus May be homozygous or heterozygous
Classification of genetic diseases
Define the term Mendelian and non Mendelian
Mendelian/Monogenic: A disease caused by a single gene with little or no impact from the environment
Non Mendelian/Polygenic: diseases or traits caused by the impact of many different genes each having a small impact on the final condition
Classification of genetic disease
Define the term “Multifactorial”
A disease or traits caused from an interaction between multiple genes or often multiple environmental factors
What is linkage analysis?
- A method used to map the location of a disease gene in the genome
- The term “Linkage” refers to the assumption of two things being physically linked to each other
What is the importance of maps?
Maps provide a context to orientate yourself and calculate distance between landmarks
Compare and contrast between genetic mapping and physical mapping
- Genetic maps look at information in blocks or regions
- Physical maps provide information on the physical distance between landmarks based on their exact location
What are the principles of genetic linkage?
- Genetic linkage is the tendency for alleles at neighbouring loci to segregate together at meiosis
- Cross overs occur more likely between loci separated by some distance than between loci close together on a chromosome
- Therefore to be linked, two loci must lie very close together
- A haplotype defines multiple alleles at linked loci. These chromosomal segments can be tracked through pedigrees and populations
Principles of genetic linkage. Give some scenarios where these principles are applied
Scenario 1:
- If a disease gene is a long distance away from a genetic marker then: independent assortment -> high likelihood of recombination
Principles of genetic linkage. Give some scenarios where these principles are applied
Scenario 2
- If a disease gene is close to a marker on the same chromosome then: Non independent assortment -> larger proportion of non recombinant expected
What are the methods used for genetic linkage?
- Genotype multiple markers across the genome
- Genotype multiple family members from families with genetic trait
- Identify which genetic markers co segregate with the disease
- These genetic markers are therefore linked to the disease gene
Summary: Recap
Genetic variation can have different phenotypic effects or can be ‘silent’
●Mutations causing Mendelian (monogenic) disease are typically rare, whilst polymorphisms are common in the population
●Homologous recombination during meiosis results in exchange of chromosome segments and new allele combinations
●Linkage analysis is a powerful method of localising a Mendelian disease gene to a specific region of the genome
●Polymorphic genetic markers can be used to identify regions of the genome that are co-segregating with the disease or phenotype
