Principles of Behavioral Genetics 3: Forward and reverse genetic approach

Question 1

____ genetics identify genes associated with a particular phenotype (can be natural or mutagen created), while ____ genetics analyze the phenotype of an organism after disrupting some genes

Answer 1

forward; reverse

Question 2

Forward genetics = ____ -> ____
(I have a (1st column) that I’m interested in, I look for the (2nd column) that underlies it)
Reverse genetics = ____-> ____
(I have a known (1st column) and I look for changes in (2nd column))

Answer 2

behavior –> genes
genes –> behavior

Question 3

What are knockouts and what do we study with them?

Answer 3

Genetically modified organisms that have a missing or disrupted gene or part of a gene. They are used in reverse genetics to study the changes in behavior associated with the gene

Question 4

What are knockdowns?

Answer 4

Without knocking a gene out but manipulate the expression of a gene (RNA interference) – can manipulate the expression of a target gene in an animal of any age at any time

Question 5

What are some forward genetic approaches commonly used today?

Answer 5

• Quantitative trait locus analysis
• Twin studies
• Genome Wide Association Studies (GWAS)
• Transcriptome analysis

Question 6

____ linkage studies use family pedigrees to look for associations between a phenotype and family history, whereas ____ linkage studies use families or populations to look for associations between a trait and genetic markers

Answer 6

phenotypic; genotypic

Question 7

____ is an example of genetic marker that has repetitive ____ of DNA that vary greatly between individuals. ____ is another example of genetic markers that varies in the sequence of a ____ ____ position in the genome (eg. A instead of C)

Answer 7

microsatellites; sequence; SNPs; single nucleotide

Question 8

GWAS states for ____ ____ ____ ____, with the goal of studying a large number of genetic polymorphisms (usually _ _ _) in a population to see which are associated with a trait

Answer 8

genome wide association study; SNPs

Question 9

SNP detection methods:
- ____ throughput: sequencing of individual stretches of DNA that potentially contain SNPs (ex. PCR)
- ____ throughput: ____ (SNP chips available for model organisms – need prior knowledge of possible SNPs), or sequencing of entire genomes or parts of genomes without knowing possible SNPs

Answer 9

low; high; microarray

Question 10

In ____, each known SNP represented by short sequence “probe” – if you have a known SNP, labeled DNA will stick, you get a ____ spot!

Answer 10

microarray; glowing

Question 11

Flint summary

Question 12

what is a p-value

Answer 12

the probability of obtaining test results at least as extreme as the results actually observed

Question 13

What p value is used as a cutoff and why?

Answer 13

0.05

Question 14

What is an R^2 value?

Answer 14

Coefficient of Determination
“proportion of the variation in the dependent variable that is predictable from the independent variable”
*higher = more points on regression = independent variable explains more variation in dependent variable

Question 15

A low ___-____ = can ____ the null hypothesis = ____ is equal to zero (no effect)

Answer 15

P-value; reject; coefficient

Question 16

What is effect size?

Answer 16

The magnitude of the different between groups

Question 17

Hypothesis of Rietveld paper

Answer 17

There are genetic variants (SNPs) with measurable effects on cognitive traits such as educational attainment

Question 18

Methods of Rietveld paper

Answer 18

Microarray SNP screens – gave questionnaires to all individuals on level of educational attainment. Started with initial 100,000 individuals (discovery sample) and then replicated it with a new sample of 25,000 individuals

Question 19

Main results from Rietveld paper

Answer 19

2 SNP significant for EduYears, 1 SNP significant for college attendance. All three were resplicated in the smaller pool

Question 20

In Rietveld paper: Why are SNP effects so small?

Answer 20

While the authors suggest the behavior is not hard to measure, genetic architecture is complex and many genes can contribute some small effect that can alter the phenotype. Other types of genetic variants besides SNPs should also be considered

Question 21

The ____ SNPs were included in the Rietveld paper, the ____ R^2 value, suggesting that…

Answer 21

more; higher; as more SNPs are involved it produced higher coefficient of correlation of the variation. (although only 1-2%)

Question 22

The Rietveld paper did find ____ and ____ associations between a few _ _ _ and educational attainment, so overall the paper ____ the hypothesis (SNPs can affect cognitive traits like educational attainment)

Answer 22

significant; replicable; SNPs; support

Question 23

What was good about the Rietveld paper

Answer 23

large sample size and replicable

Question 24

What could be improved about the Rietveld paper

Answer 24

control of SES factors, and could measure additional cognitive and behavioral variables and look for associations with same SNPs

Question 25

What would be a food follow up study for Rietveld paper

Answer 25

More in-depth investigation of the roles of identified genes -- what do they actually do? What types of cognitive functions/personality traits do they affect?