Chapter 9: Identifying Genes Flashcards
What are three types of DNA mutations? (3)
- Substitution. 2. Insertion/Deletion (Indels). 3. Expanded Triplet Repeats.
What are indels?
When an base pair is added or deleted.
What is a frameshift?
When an indel is less than 3, which causes an entire shift in the reading frame that may lead to an entirely new translation.
What is an expanded triplet repeat?
When genes feature repeat sequences (of variable numbers).
What is an example disease caused by expanded triplet repeats? What gene is involved?
Fragile X syndrome. FMR1 is repeated.
Are polymorphisms considered mutations?
No.
What is a single nucleotide polymorphism (SNP)?
A single base pair that varies in at least 1% of the population.
Where are the two regions where SNPs can be found?
- Coding region of the gene. 2. Non-coding region of the gene.
Within the coding region, what kind of SNPs can there be? (2)
- Synonymous. 2. Non-synonymous.
What are synonymous SNPs?
When there is not a change in the amino acid created.
What are non-synonymous SNPs?
When there is a change in the amino acid created.
What kind of SNPs are we looking for?
Non-synonymous SNPs in the coding region.
What is a non-common DNA variant?
SNPs that occur rarely in the population (less than 5%).
What are copy number variants? Are they mutations?
Duplication or deletion of long stretches of DNA. Yes, because they are not inherited.
What is a linkage study?
Uses family members to examine whether specific DNA markers are linked to a trait.
What is a candidate gene association study?
Focuses on a single gene or SNP and how its alleles correlate with a trait or SNP in question.
What is a Genome-wide association study (GWAS)?
Identifies SNPs that occur more frequently in people with a particular trait/disease than in people without.
What is a SNP microarray?
A procedure that sequences only a part of the genome and amplifies it.
What is a haplotype block?
A series of SNPs that are very highly correlated (i.e. seldom separated by recombination).
What is a haploid genotype (haplotype)?
The DNA sequence on one chromosome.
What are some limitations of GWAS? (4)
- Measurement. 2. Development (changes over time). 3. Clinical utility. 4. Doesn’t account for GxE interactions.
What are polygenic scores?
A formula that aggregates the weighted small effects of many DNA variants associated with a quantitative trait using GWAS results.
What do polygenic scores reflect?
A person’s genetic standing on a quantitative trait.
How are polygenic scores generally obtained? (3)
- Obtaining a discovery sample. 2. Using that sample on a target sample. 3. Observing the unique polygenic score in each person in the population.
What is first method to derive polygenic scores using GWAS?
Weighing each tiny SNP above the significance line (less than .05) by its effect size (B) and sum them together.
What is the second method to derive polygenic scores using GWAS?
By weighing each SNP above a lower significance line (.05) by its effect sized and summing them together.
What are three promising results of polygenic scores?
- More powerful predictive testing. 2. Capturing the full range of variation in a quantitative trait. 3. Thinking positively.
Do polygenic scores map to self-report measures of neuroticism?
Yes.
Are polygenic scores clinically useful yet? Why?
No, effect sizes are small and mental disorders are not completely heritable.
How much of the phenotypic variance of ADHD can be explained using polygenic scores?
.7%.
What are the three perils of polygenic scores?
- They can be manipulated (no standard p-value). 2. Not clinically useful. 3. No accounting for GxE interplay.
How are polygenic scores calculated?
The sum of an individual’s number of risk alleles times their effect size.
What is premutation for Fragile X syndrome?
Between 40 and 200 repeats of FMR1.
What are quantitative trait loci (GTLs)?
Genes of various effect sizes in multiple-gene systems that contribute to quantitative (continuous) variation in a phenotype.
What can linkage analyses be useful for?
For single gene disorders.
What is a linkage analysis?
A technique that detects linkage between DNA markers and traits.
What is linkage analysis used for?
To map genes to chromosomes.
