Week 9 (Low-Pass Sequencing & GWAS) Flashcards
we transmit ___________ to the next generation NOT alleles
chromosomes
what biological process occurs that allows us to impute genotypes on the chromosome?
in meiosis crossing over occurs, because chromosomes are transmitted from one generation to the next the probability is that is came from an ancestor
what is low-pass sequencing?
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.
GWAS
Genome-Wide Association Study
what is GWAS?
experimental design used to detect association between genetic variants and measured trait
monogenic
Mendelian = 1 “gene” (one allele causing a disease, a mendelian disease)
multigenic
more than 1 “gene” (but not many)
polygenic
many “genes”
what types of diseases are most common: monogenic, multigenic, or polygenic?
polygenic
T or F: association does not equal causation
- True!
- some correlation between variables (genotype and phenotype) does not mean that the genotype CAUSES the phenotypes
GWAS identifies association NOT what ______ them
causes
the ability to detect associations depend on:
- how many loci affecting the trait segregate in the population
- the effect size and allele frequency on those loci (genetic architecture)
- sample size
- the nature of the markers used (number and allele frequency)
- heterogeneity of the trait
the ability to detect associations depend on: (simplified)
- how many loci
- the effect size and allele frequency
- sample size
- the nature of the markers used
- heterogeneity of the trait
the ability to detect associations depend on - what two types of genetic architecture?
- how many loci
- the effect size and allele frequency
the ability to detect associations depend on - what is the most important?
sample size
what is a p-value?
the probability of obtaining test results at least as extreme as the results actually observed, under the assumption the hull hypothesis is correct
what is the null hypothesis?
mean phenotypes for individuals with genotype AA, AB, and BB are not different
what is the alternate hypothesis?
at least one of the means is different
what is the intended use of p-values in science?
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
what causes an association between a genetic marker and phenotypic trait?
linkage disequilibrium
what determines the proportion of AA, AB, BB individuals in the sample?
allele frequency
______________ __________ is the non-random association of alleles at different loci in a given population
linkage disequilibrium
linkage disequilibrium
the non-random association of alleles at different loci in a given population
___________ is the ultimate source of variation
mutation
as loci are located further apart is it more or less likely for recombination to occur?
the further apart the loci are, the more likely recombination is to occur
What kind of plot is this?
GWAS Manhattan Plot
what is a significance threshold?
a certain number or defined threshold that allows you to decide that everything above the threshold is significant data
in this Manhattan plot, what causes the patterns like the one that has been circled?
linkage disequilibrium, the haplotypes are passed down by generations and there is some impact occurring
how do we make our Manhattan plot show more obvious signs of variants?
increasing the number of individuals sequenced (statistical power)
!!! power is influenced by:
- sample size
- distribution of effect sizes
- frequency
- LD (linkage disequilibrium)
success (of GWAS) is determined:
- how many loci
- genetic architecture
- sample size
- number of variants
- heterogeneity of trait
_______ traits almost always are due to many genes, each with potentially many variants
complex
does one gene equal one protein?
NO, one gene can make many proteins due to splicing
__________ has made things now possible that were not possible, or were too expensive
technology
two types of heritability
- broad sense
- narrow sense
how can you increase linkage disequilibrium and the casual variants?
increase marker density
more markers = ________ linkage disequilibrium
higher
what would cause additive variance to be high? what would cause additive variance to be low?
- 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
does genomic selection double the rate of genetic gain?
yes!
