Genetic Variation

Question 1

Phylogenetic Tree

Answer 1

show evolutionary distance between species and even within species

Question 2

Reasons the Mouse is a Good Model for Human Studies

Answer 2

~40% of genome is perfectly aligned, ~80% of mouse genes have a single human counterpart, mutation rat is twice as high in mouse genome

Question 3

ortholog

Answer 3

gene differs in sequence but its main function is conserved across species

Question 4

homolog

Answer 4

protein sequence identical

Question 5

Outgroup

Answer 5

the least related to the other species in a phylogenetic tree (think wolves in a dog breeds tree)

Question 6

How much of the genetic sequence is shared between humans and chimpanzees?

Answer 6

99.8%

Question 7

What three factors resulted in humans and chimps being different?

Answer 7

1. Protein evolution (small (0.2%), critical changes)
2. Gene regulation
3. Less is more

Question 8

Does a species become more or less genetically diverse over time?

Answer 8

MORE genetically diverse (assuming random mating and stable population)

Question 9

Bottleneck

Answer 9

a way to reduce genetic diversity (for example, creating breeds) (eliminates some alleles in some breeds)

Question 10

Is there more genetic diversity within a breed or between breeds?

Answer 10

BETWEEN breeds

Question 11

How can you reintroduce genetic diversity to a population?

Answer 11

cross-breeding

Question 12

Comparing Humans?

Answer 12

can be done at individual or population level; 1 million variants are unique to each population, but still shared within the population

Question 13

How many base pairs in the human genome?

Answer 13

~3 billion

Question 14

Recombination vs Mutation

Answer 14

Recombination is a result of variability that is ALREADY PRESENT in the population.

Mutations introduce NEW VARIABILITY to the population.

Question 15

Types of Variants/Mutations (3)

Answer 15

1. Sequence Variants
2. Structural Variants
3. Chromosomal Abnomalities

Question 16

Trisomy 21

Answer 16

extra chromosome 21, results in Down’s Syndrome

Question 17

Chromosomal Fusion

Answer 17

part of one chromosome ran away from home to join another chromosome

Question 18

Reciprocal Translocation

Answer 18

“The Holiday” - two chromatids swapped homes

Question 19

Single Nuclotide Polymorphism (SNPs), aka point mutation

Answer 19

single base pair change

Question 20

Minor Allele Frequency

Answer 20

how often does the less common allele [of a SNP] occur within a population
>5-10% MAF = common variant
<1% MAF = rare variant

Question 21

Are the majority of SNPs non-functional?

Answer 21

yes

Question 22

Synonymous SNP

Answer 22

has no effect (non-functional, silent)

Question 23

Non-Synonymous SNP

Answer 23

results in direct change to normal gene product, possibly via change of AA, loss/gain of start or stop codon, or changing a splicing site

Question 24

Can SNPs have indirect effects?

Answer 24

potentially, through change in regulatory sequences (like in a promoter region)

Question 25

Nonsense mutation

Answer 25

SNP results in a STOP codon

Question 26

Missense

Answer 26

results in a different nucleotide, can be conservative (same type of AA) or nonconservative

Question 27

INDEL

Answer 27

structural variant; insertions/deletions of 1-10k bases within a sequence (INDEL because they commonly happen together one respective chromosomes but don't have to)

Question 28

In-Frame Mutation

Answer 28

an effect of INDEL that occurs in multiples of three, therefore just shifting the codons and all other AA remain unchanged

Question 29

Frame Shift

Answer 29

INDEL in anything other than a multiple of 3, resulting in changed AAs and typically a premature stop codon

Question 30

Effect of INDEL on product?

Answer 30

altered protein product or no product at all

Question 31

Copy Number Variant

Answer 31

structural variant; deletion or duplication of segments of DNA much larger than an INDEL (1-3kb), can affect the entire gene, problem due to mispairing in areas of repeat sequence

Question 32

CNV in Mice?

Answer 32

olfactory genes! so they can smell hella good

Question 33

Effect of CNV

Answer 33

can be postive, neutral, or negative

Question 34

What % of mutations are sequence variants/SNPs?

Answer 34

~80%

Question 35

What % of genetic mutations are structural variants?

Answer 35

~20%

Question 36

Types of Structural Variants

Answer 36

INDEL Copy Number Variants Inversions

Question 37

Inversion

Answer 37

entire segment of chromosome gets flipped around; recombination can no longer occur in this region; gene expression and phenotype can be normal as long as the inversion isn't part ofthe gene or regulatory elements

Question 38

What structural variation can be used to trac speciation?

Answer 38

inversions (ex: rats and mice)

Question 39

Effects of Inversions

Answer 39

if located within a gene or regulatory region: frequently lethal or sterility but also tobianos color in horses (and other phenotypic changes)

Question 40

trait

Answer 40

measurable/observable characteristic very generalized

Question 41

phenotype

Answer 41

observed category of a trait ex: if the trait is coat color, the phenotype is red

Question 42

Qualitative trait

Answer 42

few measured categories ex: all or nothing disease, coat color

Question 43

Quantitative trait

Answer 43

trait with continuous scale ex: speed, weight

Question 44

Sequencing

Answer 44

determine exact order of base pairs in a segment of DNA

Question 45

Markers/SNP Chips

Answer 45

common variants within a genome that can be specifically assayed instead of sequencing the entire genome

Question 46

Haplotypes

Answer 46

ordered genotyped bases; can look at variation over a larger scale

Question 47

Linkage Analysis

Answer 47

look at haplotypes that are shared by affected individuals that are not shared by unaffected individuals to idenify region(s) that contain variants associated with a trait/disease

Question 48

Genome Wide Association Analysis (GWAS)

Answer 48

calculating the statistical association of marker frequency with the phenotype of innterest by using markers/SNP chips that have already been identified