Linkage analysis

Question 1

What does genetic variation refer to?

Answer 1

Refers to differences in the DNA sequence between individuals in a population

Question 2

What are the different effects caused by genetic variation?

Answer 2

• Alteration of amino acid sequence
• Changes in gene regulation
• Physical appearance
• Silent or no apparent effect

Question 3

Why is genetic variation important?

Answer 3

Important because:

• Underlies phenotypic differences among different individuals
• Determine over predisposition to complex diseases and responses to drugs and environmental factors
• Reveals clues of ancestral human migration history

Question 4

What are the 3 mechanisms by which genetic variation arises?

Answer 4

• Mutations/Polymorphism
• Genetic Recombination
• Gene flow

Question 5

Mutations/Polymorphism

Answer 5

-Errors in DNA replication
Germline mutation-Passed onto descendants
Somatic mutation-Not transmitted to descendants
De novo mutation-New mutations

Question 6

Genetic recombination

Answer 6

Shuffling chromosomal segments between partner chromosomes of a pair

Question 7

Gene flow

Answer 7

Movement of genes from one population to another

Question 8

What type of change is a mutation?

Answer 8

A mutation is a rare change in the DNA sequence

Question 9

What type of change is polymorphism?

Answer 9

Polymorphism is a DNA sequence variant that is common in the population

Question 10

What is the arbitrary cut off point between a mutation and polymorphism?

Answer 10

Arbitrary cut off point between a mutation and polymorphism is a minor allele frequency of 1%

Question 11

What is created by meiosis?

Answer 11

Creation of haploid gametes

Question 12

What do gametes contain?

Answer 12

Gametes contain a mixture of maternal and paternal material

Question 13

What occurs in homologous recombination and when?

Answer 13

During meiosis, Crossing over occurs where there is reciprocal breaking and re-joining of the homologous chromosomes

Question 14

What does crossing over result in?

Answer 14

Results in exchange of chromosome segments and new allele combinations

Question 15

What does the term haplotype mean?

Answer 15

A group of alleles that are inherited together from a single parent

Question 16

What are the 3 terms used in the classification of genetic diseases?

Answer 16

• Mendelian/Monogenic
• Non-mendelian/polygenic
• Multifactorial

Question 17

What is mendelian/monogenic?

Answer 17

Disease that is caused by a single gene with little or no impact from the environment

Question 18

What is non-mendelian/polygenic?

Answer 18

Diseases caused by the impact of many different genes

Question 19

What is multifactorial?

Answer 19

Diseases or traits resulting from an interaction between multiple genes and often multiple environmental factors

Question 20

What method is linkage analysis?

Answer 20

Method used to map location of a disease gene in the genome

Question 21

What is the importance of maps?

Answer 21

Maps provide a context to orientate yourself and calculate distance

Question 22

Genetic maps

Answer 22

Look at information in blocks or regions

Question 23

Physical maps

Answer 23

Provide information on physical distance between landmarks based on their exact location

Question 24

What are the principals of genetic linkage?

Answer 24

• Genetic linkage is the tendency for alleles at neighbouring loci to segregate together at meiosis
• Therefore to be linked, two loci must be very close together
• A haplotype is defines multiple alleles at linked loci
• Cross overs are more likely to occur between loci separated by some distance than those close together

Question 25

Linkage mapping using genetic markers

Answer 25

- If a marker is linked to a disease locus, the same marker alleles will be inherited by two affected relatives more often than expected by chance - If the marker and disease locus are unlinked, the affected relatives in a family are less likely to inherit the same marker alleles

Question 26

What 2 markers are used as genetic markers?

Answer 26

- Micro-satellite markers | - Single nucleotide polymorphisms

Question 27

What are micro-satellite markers?

Answer 27

Highly polymorphic short tandem repeats

Question 28

What is the difference of micro-satellites between chromosomes?

Answer 28

May differ in length between chromosomes

Question 29

Comment on the arrangement of micro-satellites

Answer 29

Relatively spaced apart

Question 30

SNP's as genetic markers

Answer 30

``` -Bi-allelic A SNP will be one of two possible bases -Less heterozygous than micro-satellites -Spaced much closer -More information ```

Question 31

How can the probability of linkage be assessed?

Answer 31

Probability of linkage can be assessed using a LOD score

Question 32

What does the LOD score assess?

Answer 32

Assesses the probability of obtaining test data if the 2 loci are linked, to the likelihood of observing the same data purely by chance

Question 33

When is there no linkage in reference to the theta score and why?

Answer 33

When theta=0.5 there's no linkage because its just independent assortment

Question 34

Relationship between LOD score and linkage

Answer 34

The higher the LOD score, the higher the likelihood of linkage LOD score greater than or equal to 3 is considered evidence for linkage LOD score less than or equal to -2 is considered evidence against linkage