Genomic Analysis/GWAS

Question 1

___% of the genome is genic (exons and introns)

Answer 1

40%

Question 2

___% of the genome encodes for proteins

Answer 2

1%

Question 3

___% of an individuals genome consists of genetic diversity

Answer 3

1%
99% shared

Question 4

______ is one of two or more alternative forms of a DNA sequence

Answer 4

allele

Question 5

_______ is a rare change to the DNA sequence that severely disrupts function and typically leads to disease
Occurs in «1% of the population

Answer 5

mutation

Question 6

_______ – a common change to the DNA sequence in which there are two or more different alleles. The minor allele occurs in >1% of the population

Answer 6

polymorphism

Question 7

Polymorphisms occur roughly every ____ to _________bp (~10-15 million polymorphisms in the genome)

Answer 7

300 to 1000

Question 8

________ is a single nucleotide variant (SNV) which occurs >1% in the population

Answer 8

SNP

Question 9

_____ and ________ are the two major types of common genetic polymorphisms

Answer 9

SNPs
indels (< 50 bp)

Question 10

___________ are repeats of short sequences of DNA and are a type of InDel

Answer 10

Short tandem repeats (STR)

Question 11

________ _____________ Includes deletions, duplications, insertions, inversions, and translocations

Answer 11

structural variation

Question 12

Copy number variations (CNVs) are a subset of structural variations that lead to a change in copy number (loss or gain) of a DNA fragment >______ bps (typically >___kb)

Answer 12

> 50 bps
typically > 1000 kb

Question 13

_______________ affect entire chromosomes (e.g., Trisomy 21)

Answer 13

aneuploidies

Question 14

SNPs occur every _____ to _________ bp

Answer 14

100 to 300

Question 15

There are ______ SNPs in the human genome

Answer 15

10 million

Question 16

____________ = a unique and stable identifier for every SNP. It links the alleles/genotypes to a chromosomal location (which is updated with each genome build)

Answer 16

rsID

Question 17

_____% of the genome is noncoding

Answer 17

80%

Question 18

___________ disease = Mendelian disease

Answer 18

Monogenic

Question 19

___________ - the range of disease presentation (e.g., mild vs. severe)

Answer 19

Expressivity

Question 20

Heritability varies by ________ and _____________

Answer 20

population
environment

Question 21

________: a physical location in the genome. Typically used to refer to a region of the genome associated with your trait of interest.

Answer 21

Locus/loci

Question 22

___________ Use family pedigrees of multiple affected individuals as genetic variants close together are linked

Answer 22

linkage analysis

Question 23

________ studies test for the statistical relationship between genotype and phenotype

Answer 23

association

Question 24

______________ analysis is best for variants with modest to high effect size

Answer 24

linkage

Question 25

Two genetic loci are ______ if they are transmitted together from parent to offspring more often than expected under independent assortment (50%)

Answer 25

linked

Question 26

Two genetic loci are in linkage _________ if this holds true (transmitted more than 50% together) at the population-level

Answer 26

disequilibrium

Question 27

______________ analysis – identifies the chromosomal location of a disease gene by looking for genetic markers that co-segregate with the disease phenotype
Simply put: Do affected individuals have a common haplotype seen more often than unaffected individuals?
We use genome-wide genetic markers (e.g., SNPs, microsatellites [STRs]) to tag loci

Answer 27

linkage

Question 28

Linkage studies report likelihood of linkage in terms of ______ _______ __________ scores

Answer 28

logarithm of the odds (LOD)

Question 29

Linkage analysis does not work well for variants with ______effect sizes typically seen in polygenic diseases

Answer 29

small effect sizes

Question 30

Complex traits are known as ____________ traits

Answer 30

polygenic

Question 31

With _____________ traits environment plays a role in etiology

Answer 31

polygenic

Question 32

______________ studies test for the statistical association between genotype and phenotype. Typically, under an additive genetic model, where each additional minor allele changes the phenotype by the same amount

Answer 32

association

Question 33

___________ gene studies test a limited number of variants/genes based on a priori information (e.g., biological hypotheses or focus on a linkage peak)
Very high false positive rate

Answer 33

candidate

Question 34

_____________ test millions of common genetic variants across the genome for a statistical relationship with your phenotype of interest

Answer 34

GWAS

Question 35

___________ regression is used to analyze GWAS

Answer 35

linear ( or logistic)

Question 36

GWAS ___________ plot is a tool to visualize our loci significantly associated with BMI

Answer 36

Manhattan
X - chromosomal location of gene
Y = statistical strength of association

Question 37

Approximately only ~_____million independent common genetic variants in the genome (in individuals of European ancestry)

Answer 37

1 million

Question 38

GWAS identify __________ of correlated SNPs in loci associated with your trait of interest. These loci may overlap genes, suggesting their importance. However, GWAS do not directly identify the causal genes in the locus.

Answer 38

clusters

Question 39

GWAS tend to name loci by their nearest ________, but this does not mean we are confident it is the causal gene

Answer 39

gene

Question 40

Binary traits/case-control outcomes (e.g., Obese vs. non-obese) are fit using a ________ regression and the beta is transformed into an ______ _______

Answer 40

logistic regression
Odds ratio (OR)

Question 41

Do GWAS studies translate well to other more diverse populations

Answer 41

No, not necessarily

Question 42

_________ ___________is a measure of an individual’s overall genetic risk or propensity for a given disease or trait

Answer 42

Polygenic Scores (PGS)

Question 43

How do you calculate a simple PRS?

Answer 43

The simplest model:
For each individual, and for each SNP, multiply the number of effect alleles (0, 1, or 2) by the effect (beta) on the trait of interest
PRS = Sum of these values (the aggregate risk for each individual)

Question 44

The higher your PRS the higher your ____________ genetic risk for the disease of interest

Answer 44

aggregated

Question 45

PRS = effect __________ x the effect (or _______) + A2E2 + A3E3

Answer 45

effect allele (0, 1, 2)
effect (beta)
Individual 1 PRS = 02.2 + 21.4 + 0*1.6 = 2.8

Question 46

More complex PRS models take into account _________-______ genetic effects and correlation between SNPs

Answer 46

genome-wide