18.04.01 Genetic definitions Flashcards
(34 cards)
Define allele frequency.
The proportion of a particular allele (or variant) among all allele copies at a given locus (ie: the number of copies of a particular allele divided by the number of copies of all alleles at the given locus in a population). Usually expressed as a percentage.
It is also the relative proportion of all alleles of a gene that are of a designated type.
What is the allele frequency used for?
Allele frequency is used to estimate the amount of genetic diversity at the individual, population, and species level.
What is an association study?
A statistical method for estimating the co-occurrence of genetic alleles with a phenotype. If an association is present, an allele will occur most commonly with the phenotype in the population than would be expected by chance. The association is independent to linkage.
What are the main differences between linkage and association studies?
Linkage
- Requires families with multiple affected individuals
- Uses microsatellites
- Marker needs to be linked to risk factor - can be Mb apart
- Identifies variants of large effect typically requiring variants in the same gene in many families to detect.
Association
- Typically employs a series of unrelated cases and controls
- Typically tests 1.5-2 million SNPs
- Marker needs to be in linkage disequiblibrium which means they should be within a few kb of each other
- Requires a common risk factor that has occurred on only a few haplotypes.
Define epistasis.
a phenomenon that consists of the effect of one gene being dependent on the presence of one or more ‘modifier genes’ (genetic background).
Define genetic fitness.
population genetics defines fitness as a propensity or probability of survival and reproduction in a particular environment usually represented by w, where w is equal to 1- the selection coefficient.
Define gene flow
The flow of genetic material between previously separate populations (of the same species), caused by migration and mating.
Define gene pool
The collection of all the alleles of all of the genes found within a freely interbreeding population.
Define genetic drift
A change in allele frequency in a given population over time due to chance (ie: offsprings alleles are random samples of those in parent). Not driven by adaptive pressures and more prevalent in small populations. Genetic drift can result in the loss of some alleles (including beneficial ones) from a population, and can have a significant impact when a population sharply reduces in size (following for example a natural disaster - bottleneck effect, or by populations splitting and forming a new colony - founder effect).
Define genetic hitch-hiking.
When an allele changes frequency because another allele which it is in linkage disequilibrium is under selection pressures.
Define genetic linkage
The tendency of genes, that are located proximal to each other on a chromosome, to be inherited together during meiosis. It has been proposed that the greater the distance between 2 linked genes, the greater the chance the non sister chromatids recombine (cross over) in the region between the genes.
Define genetic load.
The difference in fitness between the optimal individual and the average of the population.
What is a genetic screening programme?
Genetic screening programs: Any kind of test performed for:
- Systematic early detection or exclusion of a genetic disease.
- Detection of genetic predisposition or resistance to a disease.
- Determination whether a person carries a gene variant, which may produce disease in offspring.
Define genotype frequency
The number of individuals in a population with a given genotype divided by the total number of individuals in the population. Genotype frequency may be used for “genomic profiling” - to predict someone’s having a disease or a birth defect. It can also be used to determine ethnic diversity.
What is a genome wide association study?
Studies looking at associations between alleles throughout the genome and phenotypes. They are effective in detecting common alleles that contribute to the inherited component of common multifactorial diseases. Typically, the alleles identified by this approach have modest effect sizes that cannot fully account for disease susceptibility. This discrepancy may exist because it is hard to identify rare alleles with a low to modest penetrance using GWAS.
What is genomic profiling?
When genotype frequency is used for to predict someone’s having a disease or a birth defect. It can also be used to determine ethnic diversity.
Define the term haplotype.
It is the symbolic representation of a combination of linked alleles in a cluster of related genes. The term is a contraction of Haploid Genotype.
What is Hardy-Weinberg’s law?
This is an important principle in population genetics that provides a solution as to how variation is maintained in a population with Mendelian inheritance. According to this principle the frequency of alleles (gene variants) remain constant through generations in the absence of the four evolutionary forces - i.e. no natural selection, no sexual selection, no mutations, no genetic drift and no gene flow (Hardy –Weinberg equilibrium). It is used to assess risk for individuals of families with genetic disease.
Define linkage disequilibrium.
It is the non-random distribution of adjacent gene alleles into gametes (by recombination). Linkage disequilibrium is the occurrence of some combinations of alleles or genetic markers in a population more often or less often than would be expected from a random distribution.
An association can only be found between alleles and disease if the disease is in LD with a marker allele.
LD is often expressed as D. If D=0 there is no association between alleles and, in this case, the distribution of alleles in the population is as expected (randomly distributed) and dependent on the allelic frequency.
What is the LOD score?
Lod is the abbreviation for “logarithm of the odds” favouring linkage. The lod score method is employed in the statistical analyses of linkage. A LOD score of 3 or more is generally taken to indicate that two loci are linked and are close to one another. In practice, score calculations are done by computer software, e.g. LIPED program.
What is a map unit (uu)
It is a measure of genetic distance between linked genes corresponding to the recombination frequency of 1% or 1 centiMorgan (cM).
Morgan’s observation that the amount of crossing over between linked genes differs led to the idea that crossover frequency might indicate the distance separating genes on the chromosome.
Define minor allele frequency (MAF).
It is the frequency of occurrence of the least common allele at a given locus in a defined population. SNPs with MAF of 5% or more have been targeted by Hapmap project.
What is a Morgan unit?
A unit used to express the distance between genes on chromosomes. One Morgan (M) indicates a recombination possibility of 100%. A crossover value (recombination) of 10% represented by a distance of deciMorgan (dM) and a crossover value of 1% is equal to centiMorgan (cM).
Define the term mutation rate.
Frequency with which a gene changes from the wild-type to a specific mutant; generally expressed as the number of mutations per biological unit (i.e., mutations per cell division, per gamete, or per round of replication).
