Chapter 9: Identifying Genes

Question 1

What are three types of DNA mutations? (3)

Answer 1

1. Substitution. 2. Insertion/Deletion (Indels). 3. Expanded Triplet Repeats.

Question 2

What are indels?

Answer 2

When an base pair is added or deleted.

Question 3

What is a frameshift?

Answer 3

When an indel is less than 3, which causes an entire shift in the reading frame that may lead to an entirely new translation.

Question 4

What is an expanded triplet repeat?

Answer 4

When genes feature repeat sequences (of variable numbers).

Question 5

What is an example disease caused by expanded triplet repeats? What gene is involved?

Answer 5

Fragile X syndrome. FMR1 is repeated.

Question 6

Are polymorphisms considered mutations?

Answer 6

No.

Question 7

What is a single nucleotide polymorphism (SNP)?

Answer 7

A single base pair that varies in at least 1% of the population.

Question 8

Where are the two regions where SNPs can be found?

Answer 8

1. Coding region of the gene. 2. Non-coding region of the gene.

Question 9

Within the coding region, what kind of SNPs can there be? (2)

Answer 9

1. Synonymous. 2. Non-synonymous.

Question 10

What are synonymous SNPs?

Answer 10

When there is not a change in the amino acid created.

Question 11

What are non-synonymous SNPs?

Answer 11

When there is a change in the amino acid created.

Question 12

What kind of SNPs are we looking for?

Answer 12

Non-synonymous SNPs in the coding region.

Question 13

What is a non-common DNA variant?

Answer 13

SNPs that occur rarely in the population (less than 5%).

Question 14

What are copy number variants? Are they mutations?

Answer 14

Duplication or deletion of long stretches of DNA. Yes, because they are not inherited.

Question 15

What is a linkage study?

Answer 15

Uses family members to examine whether specific DNA markers are linked to a trait.

Question 16

What is a candidate gene association study?

Answer 16

Focuses on a single gene or SNP and how its alleles correlate with a trait or SNP in question.

Question 17

What is a Genome-wide association study (GWAS)?

Answer 17

Identifies SNPs that occur more frequently in people with a particular trait/disease than in people without.

Question 18

What is a SNP microarray?

Answer 18

A procedure that sequences only a part of the genome and amplifies it.

Question 19

What is a haplotype block?

Answer 19

A series of SNPs that are very highly correlated (i.e. seldom separated by recombination).

Question 20

What is a haploid genotype (haplotype)?

Answer 20

The DNA sequence on one chromosome.

Question 21

What are some limitations of GWAS? (4)

Answer 21

1. Measurement. 2. Development (changes over time). 3. Clinical utility. 4. Doesn’t account for GxE interactions.

Question 22

What are polygenic scores?

Answer 22

A formula that aggregates the weighted small effects of many DNA variants associated with a quantitative trait using GWAS results.

Question 23

What do polygenic scores reflect?

Answer 23

A person’s genetic standing on a quantitative trait.

Question 24

How are polygenic scores generally obtained? (3)

Answer 24

1. Obtaining a discovery sample. 2. Using that sample on a target sample. 3. Observing the unique polygenic score in each person in the population.

Question 25

What is first method to derive polygenic scores using GWAS?

Answer 25

Weighing each tiny SNP above the significance line (less than .05) by its effect size (B) and sum them together.

Question 26

What is the second method to derive polygenic scores using GWAS?

Answer 26

By weighing each SNP above a lower significance line (.05) by its effect sized and summing them together.

Question 27

What are three promising results of polygenic scores?

Answer 27

1. More powerful predictive testing. 2. Capturing the full range of variation in a quantitative trait. 3. Thinking positively.

Question 28

Do polygenic scores map to self-report measures of neuroticism?

Answer 28

Yes.

Question 29

Are polygenic scores clinically useful yet? Why?

Answer 29

No, effect sizes are small and mental disorders are not completely heritable.

Question 30

How much of the phenotypic variance of ADHD can be explained using polygenic scores?

Answer 30

.7%.

Question 31

What are the three perils of polygenic scores?

Answer 31

1. They can be manipulated (no standard p-value). 2. Not clinically useful. 3. No accounting for GxE interplay.

Question 32

How are polygenic scores calculated?

Answer 32

The sum of an individual's number of risk alleles times their effect size.

Question 33

What is premutation for Fragile X syndrome?

Answer 33

Between 40 and 200 repeats of FMR1.

Question 34

What are quantitative trait loci (GTLs)?

Answer 34

Genes of various effect sizes in multiple-gene systems that contribute to quantitative (continuous) variation in a phenotype.

Question 35

What can linkage analyses be useful for?

Answer 35

For single gene disorders.

Question 36

What is a linkage analysis?

Answer 36

A technique that detects linkage between DNA markers and traits.

Question 37

What is linkage analysis used for?

Answer 37

To map genes to chromosomes.