Genome Organization and Variation

Question 1

When you compare an individual’s genome to a reference genome…

Answer 1

Individuals have 3-4 million single nucleotide changes

Question 2

Single Nucleotide Variants (SNVs)

Answer 2

refer to any single nucleotide change in the genome

Question 3

Functional SNV

Answer 3

leads to amino acid change (affect protein function)

Question 4

Missense variants

Answer 4

change of an amino acid

Question 5

non-sense variants

Answer 5

change an amino acid to a stop codon

Question 6

Stop loss variants

Answer 6

lead to loss of the stop codon

Question 7

T or F: There are functional variants that disrupt a splice site

Answer 7

TRUE

Question 8

Non-functional SNV

Answer 8

no amino acid change (no effect on protein functions)

Question 9

Silent variants (non-functional)

Answer 9

change a nucleotide but not the amino acid

Question 10

Intronic variants (non-functional)

Answer 10

Introns

Question 11

Intergenic variants (non-functional)

Answer 11

between genes

Question 12

SNPs (single nucleotide polymorphism) definition

Answer 12

polymorphisms that occur in at least 1% of the population (more common than SNV)

Question 13

Mutation

Answer 13

change in genome more rare than SNP;

usually refer to a change which results in a phenotype

Question 14

Small insertions or deletions of up to 20-30 bases are called:

Answer 14

Indels (insertion/deletion);

vary in size, multiples of three are most common since they do not disrupt the reading frame

Question 15

Short Tandem Repeats (microsatellites)

Answer 15

2-12 nucleotides that can be present in 10-100 copies; more common than SNPs

Question 16

There are a lot of variations in the number of repeats of microsatellites due to:

Answer 16

errors during replication when polymerase slips

Question 17

T or F: Microsatellites can be used in forensics and linkage studies?

Answer 17

TRUE

Question 18

Transposons and retrotransposons are…

Answer 18

mobile DNA sequences

Question 19

Retrotransposons definition

Answer 19

copied into an RNA intermediate before they are reverse transcribed and inserted into the genome

Question 20

LINE (long interspersed repetitive elements)

Answer 20

encode the elements necessary for retrotransposons to make copies and insert into the genome;
17% of genome

Question 21

SINEs (short interspersed repetitive elements)

Answer 21

10% of genome;
300 bp long;
from retrotransposons

Question 22

LTRs (long terminal repeats)

Answer 22

several kilo bases in size and represent around 8% of genome;
from retrotransposon

Question 23

Retrotransposons/transposons pose a risk because…

Answer 23

can replicate and insert into the genome in places that cause harm

Question 24

Copy number variants (CNVs)

Answer 24

deletions or duplications of part of the genome that can range from 100 bp to an entire arm of a chromosome;
can be found at higher resolution than karyotyping

Question 25

Although inversions and translocations are large structural variations, they…

Answer 25

DO NOT AFFECT COPY NUMBER OF GENES

Question 26

Inversions definition

Answer 26

pieces of DNA that invert in the genome often due to recombination between repeats

Question 27

Translocations

Answer 27

exchanges of DNA between chromosomes

Question 28

______ can be used to map and find mutations that cause disease

Answer 28

Variants

Question 29

2 types of genetic mapping

Answer 29

• map based strategy which uses a set of markers spread throughout the genome
• direct approach of looking at the causal variants through genome or exam sequencing

Question 30

Linkage Studies

Answer 30

Use micro satellites;
DNA from family and sequences of 300-400 micro satellites are compared between affected and unaffected family members;
microsats that are more prevalent in the affected than unaffected are close enough to the disease allele that recombination has not occurred between them;
evaluation of microsats in the area can narrow down the portion of the genome containing the disease allele further

Question 31

Linkage Studies are successful at …

Answer 31

Identifying rare, inherited variants which are associated with severe disease in families

Question 32

GWAS (genome-wide association studies)

Answer 32

Genetic mapping using SNPs;
Advantage to GWAS is that studies can include populations and not just families;
must be large sample size and well defined phenotype

Question 33

Genome sequencing

Answer 33

Identify causal variants directly;
does not limit the type of variation that an be detected or inheritance pattern that can be studied;
Challenging to interpret large amounts of data