Linkage Analysis

Question 1

Define the term “Genetic Variation”

Answer 1

The differences in the DNA sequence’s between individuals in a population

Question 2

What are the factors that cause variation?

Answer 2

Could either be inherited or due to environmental factors (drugs, exposure to radiation)

Question 3

List the effects of Genetic Variation

Answer 3

• 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

Question 4

Why is gene variation important?

Answer 4

1. Genetic Variation underlies phenotypic differences among different individuals
2. Genetic variations determine our predisposition to complex diseases and responses to drugs and environmental factors
3. Genetic Variation reveals clues of ancestral human migration history

Question 5

List some of the mechanisms of genetic variation

Answer 5

• 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

Question 6

What is the difference between a mutation and a polymorphism? (PART 1)

Answer 6

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

Question 7

What is the difference between a mutation and a polymorphism? (PART 2)

Answer 7

• 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

Question 8

What does Meiosis and recombination produce?

Answer 8

• Haploid gametes
• These gametes contain a mixture of maternal and paternal material

Question 9

What process occurs during homologous recombination?

Answer 9

• Crossing over: The reciprocal breaking and the rejoining of the homologous chromosomes during meiosis
• Results in exchange of chromosome segments and new allele combination

Question 10

What is the difference between genotype and phenotype?

Answer 10

• Genotype is the genetic makeup of an individual
• Phenotype is the physical expression of the genetic makeup

Question 11

What is the name given to genes found in alternative versions?

Answer 11

• Alleles
• For each characteristic, an organism inherits two alleles, one from each parent. The alleles can be the same or different

Question 12

What is the difference between a homozygous and heterozygous genotype?

Answer 12

• 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

Question 13

Describe how the chromosome looks

Answer 13

• 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

Question 14

Classification of genetic diseases
Define the term Mendelian and non Mendelian

Answer 14

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

Question 15

Classification of genetic disease
Define the term “Multifactorial”

Answer 15

A disease or traits caused from an interaction between multiple genes or often multiple environmental factors

Question 16

What is linkage analysis?

Answer 16

• 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

Question 17

What is the importance of maps?

Answer 17

Maps provide a context to orientate yourself and calculate distance between landmarks

Question 18

Compare and contrast between genetic mapping and physical mapping

Answer 18

• Genetic maps look at information in blocks or regions
• Physical maps provide information on the physical distance between landmarks based on their exact location

Question 19

What are the principles of genetic linkage?

Answer 19

• 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

Question 20

Principles of genetic linkage. Give some scenarios where these principles are applied

Answer 20

Scenario 1:
- If a disease gene is a long distance away from a genetic marker then: independent assortment -> high likelihood of recombination

Question 21

Principles of genetic linkage. Give some scenarios where these principles are applied

Answer 21

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

Question 22

What are the methods used for genetic linkage?

Answer 22

• 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

Question 23

Summary: Recap

Answer 23

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