Week 9 (Low-Pass Sequencing & GWAS)

Question 1

we transmit ___________ to the next generation NOT alleles

Answer 1

chromosomes

Question 2

what biological process occurs that allows us to impute genotypes on the chromosome?

Answer 2

in meiosis crossing over occurs, because chromosomes are transmitted from one generation to the next the probability is that is came from an ancestor

Question 3

what is low-pass sequencing?

Answer 3

a cost-effective, high-throughput method that sequences an entire genome at a lower depth (typically 0.1x to 5x coverage) than traditional whole genome sequencing, relying on imputation to fill in missing information and accurately detect genetic variations.

Question 4

GWAS

Answer 4

Genome-Wide Association Study

Question 5

what is GWAS?

Answer 5

experimental design used to detect association between genetic variants and measured trait

Question 6

monogenic

Answer 6

Mendelian = 1 “gene” (one allele causing a disease, a mendelian disease)

Question 7

multigenic

Answer 7

more than 1 “gene” (but not many)

Question 8

polygenic

Answer 8

many “genes”

Question 9

what types of diseases are most common: monogenic, multigenic, or polygenic?

Answer 9

polygenic

Question 10

T or F: association does not equal causation

Answer 10

• True!
• some correlation between variables (genotype and phenotype) does not mean that the genotype CAUSES the phenotypes

Question 11

GWAS identifies association. Does it identify what causes them?

Answer 11

NO

Question 12

the ability to detect associations depend on:

Answer 12

1. how many loci affecting the trait segregate in the population
2. the effect size and allele frequency on those loci (genetic architecture)
3. sample size
4. the nature of the markers used (number and allele frequency)
5. heterogeneity of the trait

Question 13

the ability to detect associations depend on: (simplified)

Answer 13

1. how many loci
2. the effect size and allele frequency
3. sample size
4. the nature of the markers used
5. heterogeneity of the trait

Question 14

the ability to detect associations depend on - what two types of genetic architecture?

Answer 14

1. how many loci
2. the effect size and allele frequency

Question 15

the ability to detect associations depend on - what is the most important?

Answer 15

sample size

Question 16

what is a p-value?

Answer 16

the probability of obtaining test results at least as extreme as the results actually observed, under the assumption the hull hypothesis is correct

Question 17

what is the null hypothesis?

Answer 17

mean phenotypes for individuals with genotype AA, AB, and BB are not different

Question 18

what is the alternate hypothesis?

Answer 18

at least one of the means is different

Question 19

what is the intended use of p-values in science?

Answer 19

they are not to be used to substitute for scientific reasoning, they are used for illumination of data and then you must decide if you believe the statistical results

Question 20

what causes an association between a genetic marker and phenotypic trait?

Answer 20

linkage disequilibrium

Question 21

what determines the proportion of AA, AB, BB individuals in the sample?

Answer 21

allele frequency

Question 22

______________ __________ is the non-random association of alleles at different loci in a given population

Answer 22

linkage disequilibrium

Question 23

linkage disequilibrium

Answer 23

the non-random association of alleles at different loci in a given population

Question 24

___________ is the ultimate source of variation

Answer 24

mutation

Question 25

as loci are located further apart is it more or less likely for recombination to occur?

Answer 25

the further apart the loci are, the more likely recombination is to occur

Question 26

What kind of plot is this?

Answer 26

GWAS Manhattan Plot

Question 27

what is a significance threshold?

Answer 27

a certain number or defined threshold that allows you to decide that everything above the threshold is significant data

Question 28

in this Manhattan plot, what causes the patterns like the one that has been circled?

Answer 28

linkage disequilibrium, the haplotypes are passed down by generations and there is some impact occurring

Question 29

how do we make our Manhattan plot show more obvious signs of variants?

Answer 29

increasing the number of individuals sequenced (statistical power)

Question 30

!!! power is influenced by:

Answer 30

- sample size - distribution of effect sizes - frequency - LD (linkage disequilibrium)

Question 31

success (of GWAS) is determined:

Answer 31

- how many loci - genetic architecture - sample size - number of variants - heterogeneity of trait

Question 32

_______ traits almost always are due to many genes, each with potentially many variants

Answer 32

complex

Question 33

does one gene equal one protein?

Answer 33

NO, one gene can make many proteins due to splicing

Question 34

__________ has made things now possible that were not possible, or were too expensive

Answer 34

technology

Question 35

two types of heritability

Answer 35

- broad sense - narrow sense

Question 36

how can you increase linkage disequilibrium and the casual variants?

Answer 36

increase marker density

Question 37

more markers = ________ linkage disequilibrium

Answer 37

higher

Question 38

what would cause additive variance to be high? what would cause additive variance to be low?

Answer 38

- high means that most of the differences between individuals is due to DNA - low means that you would struggle to predict it because it is less about DNA and caused by the environment

Question 39

does genomic selection double the rate of genetic gain?

Answer 39

yes!