Lecture 2 and 3: Human Variation

Question 1

What determines cell type?

Answer 1

Which genes are turned on and off and when

Question 2

How many protein coding genes are there?

Answer 2

~20K

Question 3

What is Genetic Variation?

Answer 3

Variation in the sequence or structure of the human genome

Question 4

What are the 2 categories of Variation?

Answer 4

Structural and Sequence Level

Question 5

What are the Structural Variations?

Answer 5

Copy Number (deletions and duplications)
Positional (insertions and deletions)
Orientational (inversions)

Question 6

What are the Sequence Level Variations?

Answer 6

Single Base substitutions
Small deletions/duplications
Repetitive sequences

Question 7

What is Cytogenetics?

Answer 7

Looks at the structure, properties and behaviour of chromosomes

Question 8

What is Molecular Genetics?

Answer 8

Looks at the structure and function of genes at molecular level

Question 9

Does size of variation indicate the severity of the disease?

Answer 9

No

Question 10

What are the causes of variation?

Answer 10

• Environmental Agents (UV and Ionising radiation)
• Replication Errors (Proof-reading and fork stalling)
• Meiotic Recombination
• Retrotransposition (like viruses)

Question 11

Define Continuous variation:

Answer 11

Is on a spectrum (i.e. height, weight), can be shown as a line graph

Question 12

Define Discontinuous variation:

Answer 12

Exists in distinct groups (i.e. tongue rolling, blood groups), can be shown as a bar graph

Question 13

Define Locus:

Answer 13

A location of a marker/gene on a chromosome

Question 14

Define Allele:

Answer 14

One variant of a marker at a particular locus

Question 15

Define Polymorphism:

Answer 15

Change in DNA sequence that is found in >1% of a population, has a weak or no effect

Question 16

Define Mutation:

Answer 16

Change in DNA sequence that is found in <1% of a population, can produce a gain or loss of function

Question 17

Define Monogenic:

Answer 17

Change/s in 1 gene cause a disease or multiple diseases or changes in multiple genes cause a single disorder

Question 18

Define Polygenic:

Answer 18

Multiple genes contribute to the phenotype, each exerts a small effect

Question 19

Define Multifactorial:

Answer 19

Interaction of the gene with the environment causes the disease

Question 20

Define Misssense:

Answer 20

Change in function due to a change in the protein structure due to a change in the amino acid

Question 21

Define Nonsense:

Answer 21

Change in the DNA sequence cause the termination of translation (STOP codon)

Question 22

Define Frameshift:

Answer 22

Deletion or addition of an nt/s causes the reading frame to change

Question 23

Define Silent:

Answer 23

Change in the DNA sequence doesn’t cause a change in protein structure and .’. doesn’t change function

Question 24

What are the 4 ways to find a disease gene (historically):

Answer 24

• Functional cloning
• Positional Cloning
• Positional Candidate Cloning
• Candidate Gene Cloning

Question 25

What is Functional Cloning?

Answer 25

ID of the genes through the knowledge of the primary biochemical defect in the disease

Question 26

What is Positional Cloning?

Answer 26

ID of the genes through the knowledge of the position of the disease gene