L4 GWAS Flashcards
GWAS
Genome wide association studies
is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait.
Which genetic polymorphisms in a population correlate with a particular phenotype in a population?
Identify variants in LD with causal variants
- large population sample
- genotyped at many loci (millions +)
- phenotype
- statistical tests for correlation
- need to correct for multiple tests when considering “significance”
Heritability
Heritability is a statistic used in the fields of breeding and genetics that estimates the degree of variation in a phenotypic trait in a population that is due to genetic variation between individuals in that population
Parent offspring regression
In the parent–offspring regression method, the heritability (resp. half of the heritability) of a trait is given by the slope of the regression between the mid‐parent phenotype (resp. the phenotypes of one of the parents) and the mean offspring phenotype.
Narrow sense heritability
‘narrow sense heritability’ (h2) is defined as the proportion of trait variance that is due to additive genetic factors.
PO regression is narrow sense heritability; the linear component represents that variation which is additive
Broad sense heritability
‘broad sense heritability’ (H2) is defined as the proportion of trait variance that is due to all genetic factors including dominance and gene-gene interactions.
Quantitative trait
A quantitative trait is a measurable phenotype that depends on the cumulative actions of many genes and the environment. These traits can vary among individuals, over a range, to produce a continuous distribution of phenotypes. Examples include height, weight and blood pressure.
Qualitative trait
A qualitative trait is a feature, that is either present, or not present, depending on whether the gene responsible for that trait is present (or functional) or absent (or non-functional). An example for a qualitative trait is flower color, which could be red, brown, green, or yellow.
QTL Mapping
QTL mapping is a method utilized to define the general chromosomal position of genes or genetic variants that influence the magnitude of a measurable trait.
- Markers that you follow through a family’s pedigree
- Limited to the parental line, variation seen is only ones from the one bi-parental cross
- Limited recombination, can only map to a certain resolution
- Mapping to a broad region, can have two factors that contribute to a trait next to each other but would be unable to identify it, need a smaller region
- Dominance
- Causal factors that counteract each other
Things aren’t additive
Genotype
The genotype is the set of genes in our DNA which is responsible for a particular trait.
Phenotype
The phenotype is the physical expression, or characteristics, of that trait.
Hardy-Weinberg Equilibrium
states that allele and genotype frequencies in a population will remain constant from generation to generation in the absence of other evolutionary influences.
Additive genetic effects
Additive genetic effects occur when two or more genes source a single contribution to the final phenotype, or when alleles of a single gene (in heterozygotes) combine so that their combined effects equal the sum of their individual effects.
Additive genetic variance involves the inheritance of a particular allele from your parent and this allele’s independent effect on the specific phenotype, which will cause the phenotype deviation from the mean phenotype.
Dominant genetic effects
Dominance in genetics is a relationship between alleles of one gene, in which the effect on phenotype of one allele masks the contribution of a second allele at the same locus.
Dominance genetic variance refers to the phenotype deviation caused by the interactions between alternative alleles that control one trait at one specific locus
Epistasis
The term epistasis describes a certain relationship between genes, where an allele of one gene (e.g., ‘spread’) hides or masks the visible output, or phenotype, of another gene (e.g., pattern).
Epistatic variance involves an interaction between different alleles in different loci.
Genetic Variance
Genetic variance has three major components: the additive genetic variance, dominance variance, and epistatic variance.[3]
Phenotypic variance
Phenotypic variance, usually combines the genotype variance with the environmental variance.
Minor allele frequency
Minor allele frequency (MAF) refers to the frequency at which the second most common allele occurs in a given population.
Central limit theorem
In probability theory, the central limit theorem (CLT) establishes that, in some situations, when independent random variables are added, their properly normalized sum tends toward a normal distribution (informally a “bell curve”) even if the original variables themselves are not normally distributed.
T-test
The t test is one type of inferential statistics. It is used to determine whether there is a significant difference between the means of two groups.
p-value
The P value, or calculated probability, is the probability of finding the observed, or more extreme, results when the null hypothesis (H 0) of a study question is true – the definition of ‘extreme’ depends on how the hypothesis is being tested.
A small p-value (typically ≤ 0.05) indicates strong evidence against the null hypothesis, so you reject the null hypothesis. A large p-value (> 0.05) indicates weak evidence against the null hypothesis, so you fail to reject the null hypothesis.
Manhattan plots
Manhattan plots represent the P values of the entire GWAS on a genomic scale (Fig. 2a). The P values are represented in genomic order by chromosome and position on the chromosome (x-axis). The value on the y-axis represents the −log10 of the P value (equivalent to the number of zeros after the decimal point plus one).
Allelic effect
An allelic effect size is the magnitude of the effect of an allele on a phenotype.
Linkage disequilibrium
linkage disequilibrium is the non-random association of alleles at different loci in a given population.
Haplotype
A haplotype (haploid genotype) is a group of alleles in an organism that are inherited together
Chromosome
a thread-like structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes.
Drosophila Genetic Reference Panel
The Drosophila Genetic Reference Panel (DGRP) is a population consisting of more than 200 inbred lines derived from the Raleigh, USA population. The DGRP is a living library of common polymorphisms affecting complex traits, and a community resource for whole genome association mapping of quantitative trait loci.
Pleiotropy
Pleiotropy occurs when one gene influences two or more seemingly unrelated phenotypic traits.
Transcriptomics
The key aims of transcriptomics are: to catalogue all species of transcript, including mRNAs, non-coding RNAs and small RNAs; to determine the transcriptional structure of genes, in terms of their start sites, 5′ and 3′ ends, splicing patterns and other post-transcriptional modifications; and to quantify the changing expression levels of each transcript during development and under different conditions.
Metabolomics
Metabolomics is the large-scale study of small molecules , commonly known as metabolites, within cells, biofluids, tissues or organisms
Partial dominance
In genetics, incomplete or semi-dominance; the production of an intermediate phenotype in individuals heterozygous for the gene concerned. Partial dominance is generally considered to be a type of incomplete dominance, with the heterozygote resembling one homozygote more than the other.
Penetrance
the percentage of individuals with a given genotype who exhibit the phenotype associated with that genotype.
Variable expression
It describes the phenomenon of differing clinical features or phenotype among individuals carrying the same gene allele or genotype. Expressivity differs from penetrance, which describes the probability that a genetic variation (or allele) will yield the phenotype at all.
Dichotomous traits
Dichotomous is a trait that separates completely a set of living organisms that belong to the same species. To put it simply an organism either has or it hasn’t this trait. This is in contrast with continuous traits where there aren’t any discrete categorizations. For example, blood type (A, B or O) are dichotomous traits whereas height, weight, life span and skin color are continuous traits.
Heritability
Heritability is a statistic used in the fields of breeding and genetics that estimates the degree of variation in a phenotypic trait in a population that is due to genetic variation between individuals in that population.
