GENETICS - Applied Genetics Flashcards
What is a pedigree?
A pedigree is a record of genealogical data for an animal
What are the five main purposes of a pedigree?
Confirmation of identity
Breeding for specific traits/avoiding undesirable traits
Suggests mode of inheritance for specific traits
Estimation of inbreeding coefficients
Management of small or fragmented populations to minimise inbreeding
Interpret this pedigree notation
Male
Interpret this pedigree notation
Female
Interpret this pedigree notation
Mating
Interpret this pedigree notation
Dizygotic twins (non-identical)
Interpret this pedigree notation
Monozygotic twins (identical)
Interpret this pedigree notation
Affected individuals
Interpret this pedigree notation
Heterozygotes for autosomal recessive mutation
Interpret this pedigree notation
Carrier individual
Interpret this pedigree notation
Dead individual
Interpret this pedigree notation
Propositus
What does propositus mean?
Propositus is the first individual to present with a specific phenotype or condition
What are Mendelian genetics?
The study of certain patterns of how traits are passed from parent to offspring
What is autosomal recessive inheritance?
Autosomal recessive inheritance is when an individual inherits two mutant recessive alleles from carrier parents
Why are autosomal recessive diseases so common?
Both parents are carriers so often breeders don’t realise that these individuals are carrying mutant alleles before breeding them and producing offspring which may express the disease
List three examples of autosomal recessive diseases
Leukocyte adhesion deficiency
Von Willebrands disease
Severe combined immunodeficiency in horses (SCID)
What are some of the key features seen in autosomal recessive inheritance?
Males and females affected at an equal frequency
25% of offspring likely to be affected
Both parents of affected offspring are carriers
What is autosomal dominant inheritance?
Autosomal dominant inheritance is when an individual inherits one mutant dominant allele from one heterozygous parent carrying the mutation
Why are autosomal dominant diseases so rare?
The parent carrying the mutation is heterozygous so the disease is phenotypically expressed and most breeders won’t breed an individual with a genetic disease
Give an example of an autosomal dominant disease
Hyperkalaemic periodic paralysis (HYPP) in horses
Which complication can arise that makes autosomal dominance diseases slightly more common?
Incomplete penetrance
What is incomplete penetrance?
Incomplete penetrance is when an individual carries a disease but does not express the disease phenotype
Give an example of an autosomal dominant disease with incomplete penetrance
Polycystic kidney disease in cats
What are some of the key features of autosomal dominant inheritance?
Males and females affected at an equal frequency
50% of offspring likely to be affected
Affected offspring have an affected parent
Why is there no male to male offspring transmission in X-linked recessive inheritance?
There is no male to male offspring transmission as the male offspring inherits the Y gene from his father and the X gene from his mother
What are some of the key features of X-linked recessive inheritance?
No male to male offspring transmission
Affects alternate generations
What are quantitative traits?
Quantitative traits are phenotypes with continuous variation, meaning traits that can take a range of values rather than being limited to distinct categories
What is locus heterogeneity?
Locus heterogeneity is when a single phenotype can be derived from mutations on multiple different loci
Give an example of a disease caused by locus heterogeneity
Hypertrophic cardiomyopathy in cats
What is allele heterogeneity?
Allele heterogeneity is when different phenotypes can be derived from multiple mutations at a single locus
Give an example of a disease caused by allele heterogeneity
Double muscling in cattle
What is the general definition of inbreeding?
Inbreeding is the mating of relatives more closely related than the average for the population
Inbreeding increaes homozygosity. What is homozygosity?
Homozygosity is when an individual carries two identical copies of allele for a particular gene
What are the three consequences of inbreeding?
Prepotency
Inbreeding depression
What is prepotency?
Prepotency is the greater ability of one parent to consistently pass on its traits to its offspring
What is inbreeding depression?
Inbreeding depression is a decrease in fitness and health of the offspring due to the increased likelihood of inheriting harmful genetic traits
What percentage of pedigree inbreeding is acceptable within a population?
Less than 6.25%
What is population genetics?
Population genetics is a subfield of genetics that deals with the genetic varaition within and among populations
What is genetic diversity?
Genetic diversity is the variety of genetic information within a population or species
Why is it important to be able to quantify genetic diversity in veterinary medicine?
Quantifying genetic diversity allows us to gain insights into the genetic makeup of different animals populations, which is essential for breeding programmes, disease management, preventing the spread of genetic disorders and conservation efforts
What are the two commonly used markers used to quantify genetic diversity?
Microsatellites
Single nucleotide polymorphisms (SNPs)
What are microsatellites?
Microsatellites are repeated sequences of 2-5 DNA base pairs with variable number of repeat units located within the introns of genes
What are single nucleotide polymorphisms (SNPs)?
Single nucleotide polymorphisms (SNPs) are locations on the genome where a measurable proportion of the population has one nucleotide and the remainder of the population has another nucleotide
What are some of the possible functional consequences of single nucleotide polymorphisms (SNPs)?
Some single nucleotide polymorphisms (SNPs) have functional consequences that can lead to changes in the amino acid and thus protein sequence (non-synonymous substitution) or alter gene expression. These changes can directly affect how the protein functions or how much of the protein is produced
What increases the possibility of functional consequences due to single nucleotide polymorphisms (SNPs)?
SNPs located in an exon of a gene
Non-synonymous SNPs can directly change the amino acid sequence of a protein
Why are single nucleotide polymorphisms (SNPs) located in exons of a gene more likely to have functional consequences?
When a single nucleotide polymorphisms (SNP) is located in the exon of a gene, it has a higher chance of functional consequences as exons code for protein sequences
Why are non-synonymous single nucleotide polymorphisms (SNPs) more likely to have functional consequences?
Non-synonymous single nucleotide polymorphisms (SNPs) can directly lead to changes in the amino acid and thus protein sequence (non-synonymous substitution)
How are single nucleotide polymorphisms (SNPs) detected for quantifying genetic diversity?
SNPs are detected for quantifying genetic diversity through genetic sequencing or using species specific SNP chips labelled with DNA propes
What are indels?
Indels are a collective term for insertion and deletion mutations
What are haplotypes?
A haplotype is any combination of alleles at multiple loci on the same chromosome. These alleles can be a combination of SNPs, microsatellites and/or indels
*Remember, alleles are variations in DNA base pairs at specific loci of gene encoding for different traits, and SNPs, microsatellites and indels are all variations in DNA base pairs *
When are two homologous chromosomes considered to have the same haplotype?
Two homologous chromosomes are considered to have the same haplotype if both chromosomes share the same allele at each of the loci under consideration
When are two homologous chromosomes considered to have a different haplotype?
Two homologous chromosomes are considered to have a different haplotype if any of the alleles are different at each of the loci under consideration
Why is studying haplotypes important in population genetics?
Studying haplotypes allows us to understand how genetic variations are distributed among different populations as well as evolutionary history of that population
What is a gene pool?
A gene pool is the total number of all alleles within the breeding population
What is the Hardy-Weinberg equilibrium (HWE)?
The Hardy-Weinberg equilibrium (HWE) is the condition in which both gene (allele) and genotype frequencies in a population remain constant from generation to generation unless acted upon by evolutionary factors
What is the difference between gene (allele) and genotype frequencies?
Gene (allele) frequency refers to the proportion a specific allele at a specific locus within a population. Genotype frequency refers to the proportion of individuals within a population that have a particular genotype
What are the five assumptions of Hardy-Weinberg equilibrium (HWE)?
Random mating
Absence of selection
Absence of mutation
Absence of migration
Absence of genetic drift
What is the Hardy-Weinberg equilibrium (HWE) equation for gene/allele frequency?
p + q =1
p is the dominant allele frequency within a population
q is the recessive allele frequency within a population
What is the Hardy-Weinberg equilibrium (HWE) equation for genotype frequency?
p² + 2pq + q² = 1
p² is the homozygous dominant genotype
2pq is the heterozygous genotype
q² is the homozygous recessive genotype
What are the five indicies used to express genetic diversity?
Percentage of polymorphic loci (P)
Number of alleles (A)
Observed heterogeneity (Ho)
Expected heterogeneity (He)
Allelic richness or effective allele number (Ae)
What is the percentage of polymorphic loci (P)?
The percentage of polymorphic loci (P) refers to the proportion of the population that has a different alleles at a specific genetic loci, indicating the level of genetic diversity within a population
What is observed heterozygosity (Ho)?
Observed heterozygosity (Ho) refers to the actual proportion of individuals in a population that have two different alleles at a specific gene locus
What is expected heterozygosity (Ho)?
Expected heterozygosity (Ho) is the average probability of having two alleles at a specific gene locus
What is allelic richness or effective allele number (Ae)?
Allelic richness refers to the number different alleles present at a specific gene locus within a population. The higher allelic richness, the greater the genetic variation within the population
What is the concept of random fixation of alleles?
Random fixation of animals refers to the process by which an allele becomes either fixed or lost at a locus in all individuals within a population, with the probability of allele fixation equal to the initial frequency of that allele
What is the concept of effective population size (Ne)?
Effective population size (Ne) in genetics refers to the proportion of the population that has a chance of breeding.
How does a larger population influence the random fixation of alleles?
A larger population, the loss or fixation of heterozygosity (presence of two different alleles at a particular gene locus) is slower than in a smaller population
What are the three main purposes of parentage testing?
Confirmation of pedigree
To assign sires in multiple sire matings
Management of population genetics in wildlife
What is parentage testing?
Parentage testing refers to determining the biological parents of an animal using genetic markers which remain the same throughout the animals life and excluding impossible parents from consideration
What is parentage assignment?
Parentage assignment refers to assigning parentage to offspring based on documents and records when genetic testing is not feasible or available
What are the two catergories of genetic markers that can be used for parentage testing?
Blood typing markers
DNA markers
Which three blood typing markers are used for parentage testing?
Red blood cell antigens
Plasma proteins
Haemoglobin
Which two DNA markers are used for parentage testing?
Microsatellites
SNPs
What are the five advantages of using microsatellites as genetic markers for parentage testing?
- Well understood and validated
- High level of polymorphism at each locus so only require a small number of markers (less than 20 markers)
- Microsatellites are considered to be selectively neutral
- Microsatellite minor allele frequency are generally relatively high frequency in most breeds
- Possible to revert to the traditional system of running gels and visual analysis instead of automation or technology
How does a high level of polymorphism at each locus reduce the number of markers required when using microsatellites as genetic markers for parentage testing?
High level of polymorphism at each locus means there are many diferent versions, or alleles, of the marker at each locus. This high variability allows for more accurate discrimination between individuals and reduces the number of markers required for parentage testing
Microsatellites are considered to be selectively neutral, what does this mean and is this advantageous when using microsatellites for parentage testing?
Microsatellites are considered to be selectively neutral, meaning they are not often infleunced by natural selection meaning their proportion within a population should not change greatly over time
What is the main advantage of using SNPs as genetic markers for parentage testing?
SNPs have a high potential for automation as SNPs are a single DNA nucleotide and thus can be easily detected and analysed by automated methods. This allows for faster and more efficient processing of large numbers of SNPs, allowing for increased accuracy and speed of parentage testing. This high potential for automation makes SNPs a convenient choice for large-scale genetic analysis
What are the four disadvantages of using SNPs as genetic markers for parentage testing?
- Low level of polymorphism at each locus so require a larger number of markers (more than 100 markers)
- SNP minor allele frequency is generally too low frequency in most breeds
- Technologically dependent
- Mutations have a more significant effect as SNPs are individual nucleotides
How is the accuracy of parentage testing typically expressed?
The accuracy of parentage testing is typically expressed in terms of the exclusion probability
What is exclusion probability in parentage testing?
Exclusion probability is the probability of excluding an impossible parent from consideration
What is the desired exclusion probability for parentage testing?
Exclusion probability of more than 0.9999
Which two factors infleunce the exclusion probability in parentage testing?
Number of markers examined
Degree of variation of the markers examined
What is identity in parentage testing?
Identity is the probability that unrelated parents have an identical genotype
How can the risk of identity be reduced in parentage testing?
The higher number and variablility of markers used within parentage testing can reduce the risk of identity in parentage testing
What is the relationship between exclusion probability and identity in parentage testing?
The higher the exclusion probability, the lower the identity
What is the difference between traits and phenotype?
Traits are specific characteristics that can be inherited whereas phenotypes are the observable physical or biochemical expression of those traits
What is breeding value?
Breeding value is the value of an individual as a genetic parent
What is phenotypic selection?
Phenotypic selection is the selection of animals for breeding based on an individual’s phenotype
What is heritability?
Heritability refers to the measure of the strength of the relationship between the breeding value and phenotypic selection for a trait within a population
What is performance testing?
Performance testing is the systematic measure of phenotypic performance within a population
What is progeny data?
Progeny data is information on the genotype or performance of descendants of an individual
What are collateral relatives?
Collateral relatives are relatives that are neither direct anscestors or descendants of an individual
What is a polygenetic trait?
A polygenetic trait is a trait influenced by many genes, with no single gene having an overriding influence
What is a simply inherited trait?
A simply inherited trait is a trait influenced by only a few (1-3) genes
What is selective breeding?
Selective breeding is the process by which humans intentionally choose certain animals with desirable traits to reproduce to produce offspring with those same traits
What are selective objectives?
Selective objectives refer to the specific characteristics that breeders aim to enhance or eliminate within a population
What are selective criteria?
Selective criteria are the actual traits that breeders measure and use to select the individuals which will be the parents of the next generation
Which three methods can be used to select for multiple selective objectives?
Selection index
Tandem selection
Independent culling levels
How can a selection index be used to select for multiple selective objectives?
A selection index is a tool that combines multiple selective objectives into a single value, it assigns weights to each objective based on their importance and calculates a score for each individual. This allows breeders to make a more informed decision through considering mulitple traits simultaneously
What is tandem selection?
Tandem selection in the selection of one objective for a period of several generations followed by a switch to other objectives for several generations
How can a independent cullings levels be used to select for multiple selective objectives?
Independent culling levels allow for a threshold to be applied to each objective, and only individuals who meet or exceed these thresholds for all objectives are selected for breeding
What is the main disadvantage of independent cullings levels to select for multiple selective objectives?
Independent culling levels severly reduces the gene pool of available contributors to the next generation
What are the three main selection strategies used for selective breeding?
Selection of the most appropriate breed
Cross-breeding
Selection within a breed
What are the four benefits of cross-breeding?
Enable grading up
Complementary selection
Heterosis (hybrid vigor)
Creating a synthetic breed
How does cross-breeding allow for grading up?
By mating animals of different breeds, breeders can combine desirable traits from each breed and create offspirng with improved characteristics, known as grading up
How does cross-breeding allow for complementary selection?
Complementarity is where a new or other breed is throught to have attributes that are missing from a base breed that are otherwise desirable. Combining breeds allows for this attribute to be passed on the the next generation in combination with the desirable traits of the base breed
What is heterosis (hybrid vigor)?
Heterosis (hybrid vigor) is the phenomenon where the hybrid offspring of two different breeds exhibit superior traits and performance compared to their parents. This is due to cross-breeding and non-additive gene action
What is dominance?
Dominance is the term used when additive gene action has a positive effect, increasing heterosis (hybrid vigor) as the performance and traits of the hybrid offspring are superior to it’s parents
What is epistasis?
Epistasis is the term used when additive gene action has a negative effect, reducing heterosis (hybrid vigor) as the performance and traits of the hybrid offspring is inferior to it’s parents
What is individual heterosis (I)?
Individual heterosis (I) is the superior performance exhibited by an individual hybrid offspring comparents to it’s parents
What is maternal heterosis (M)?
Maternal heterosis (M) is the superior performance exhibited by an individual hybrid offspring due to the genetic makeup of the mother
What is the difference between two-way and three-way cross-breeding?
Two-way cross-breeding is when two different breeds are crossed, whereas three-way cross-breeding is when an additional breed is incorporated
How does two-way cross breeding influence individual (I) and maternal (M) heterosis?
Two-way cross-breeding allows for moderate to high individual (I) heterosis but no maternal (M) heterosis
How does three-way cross breeding influence individual (I) and maternal (M) heterosis?
Two-way cross-breeding allows for maximal individual (I) heterosis and maternal (M) heterosis
Which five factors infleunce the rate of selection in selective breeding?
Generation interval
Variation in breeding values
Selection intensity
Effective population size (Ne)
Accuracy of selection
What is generation interval?
Generation interval refers to the average age difference between parents and their offspring within a population
How does a shorter generation interval influence the rate of selection?
A shorter generation interval allows for a more rapid rate of selection and more rapid genetic progress within a population
How does a longer generation interval influence the rate of selection?
A longer generation interval allows for a slower rate of selection and slower genetic progress within a population
How does a greater range of breeding values within a population influence the rate of selection?
A greater range of breeding values within a population provides breeders with increased variation and thus allows for more targeted selection and thus a more rapid rate of selection and genetic progress within the population
How does a lower range of breeding values within a population influence the rate of selection?
A lower range of breeding values within a population provides breeders with decreased variation and thus less targeted selection and a slower rate of selection and genetic progress within the population
What is selection intensity?
Selection intensity refers to how strict or rigorous the selection process is
How does high selection intensity influence the rate of selection?
When selection intensity is high, only a small percentage of individuals with the desired traits will be chosen as parents for the next generation. This can lead to a faster rate of selection, as the favourable traits become more prevelant in the population over time
How does low selection intensity influence the rate of selection?
When selection intensity is low, a larger percentage of individuals with varying traits will be allowed to breed, resulting in a slower rate of selection
What are quantitative traits?
Quantitative traits are phenotypes with continuous variation, meaning traits that can take a range of values rather than being limited to distinct categories
Which two factors influence quantitative traits?
Polygenetics
Environmental factors
Why do most quantitative traits exhibit normal distribution?
Most quantitative traits exhibit a normal distribution because they are influenced by multiple genetic and environmental factors. This leads to a bell-shaped curve, where the majority of individuals fall near the average value, with fewer individuals at the extremes
Give two examples of quantitative traits that exhibit negative exponential distribution?
Adaptive traits
Immune traits
Why do some quantitative traits exhibit negative exponential distribution?
When it comes to adaptive and immune traits, a negative exponential distribution can emerge within the population because these traits often follow a pattern where the majority of individuals have a low level of adaptation or immunity (because natural selection favors individuals with traits well suited to their environment) , while fewer individuals possess higher levels of these traits
What is the additive gene effect?
The additive gene effect refers to the individual contribution of a gene to the overall variation of a phenotype, without considering gene interactions with one another
What is the gene combination effect?
The gene combination effect refers to the combines effect of gene, including dominance and epistasis, on the overall variation of a phenotyoe
What is estimated breeding value (EBV)?
Estimated breeding value (EBV) is the estimated value of a parent for breeding for a specific selection objective
What is progeny difference (PD)/predicted transmitting value (PTA)?
Progeny difference (PD)/predicted transmitting value (PTA) refers to the estimated genetic value that an animal will pass on to its offspring for a specific trait
What is the basic genetic model (equation) for any quantitative trait?
P = µ + BV + GCV + E
P = phenotypic value or performance of an individual
µ = population mean or average phenotype value within the population
BV = additive breeding value
GCV = gene combination value
E = environmental influence on an individual’s phenotypic value or performance
Which equation would you use to estimate the phenotypic value or performance of a progeny within a given or controlled environment?
Poffspring = average phenotypic value or performance of the offspring
µ = population mean or average phenotype value within the population
BVoffspring = average additive breeding value of offspring
1/2 BV sire = half of the additive breeding value of the sire
1/2 BV dam = half of the additive breeding value of the dam
Explain how this equation can be used to estimate the phenotypic value or performance of a progeny within a given or controlled environment?
The additive breeding value (BV) refers to the individual contributions of genes to a specific trait. So, when trying to predict the phenotypic value or performance of an offspring in that specific trait, we consider the additive breeding value of both the sire and the dam which will represent the individual contibution of their genes to the phenotype
Which equation can be used to apply the genetic model of a quantitative trait to an entire whole population?
BV = average additive breeding value for that trait in the population
GCV = average gene combination value for that trait in the population
G = average genotypic value
E = average environmental effect on phenotypic value or performance within the population
When the value of this equation is equal to zero, what does that indicate about the genetic and environmental factors contributing to a quantitative trait within the population?
When the value of this equation is equal to zero, it suggests the genetic and environmental factors contributing to this quantitative trait are equal, i.e. neither factor has a greater infleunce on the trait than the other
When the value of this equation is greater than zero, what does that indicate about the genetic and environmental factors contributing to a quantitative trait within the population?
When the value of this equation is greater than zero, it suggests that one of these factors, either genetic or environmental, has a greater contribution to the trait than the other
When the value of this equation is less than zero, what does that indicate about the genetic and environmental factors contributing to a quantitative trait within the population?
When the value of this equation is less than zero, it suggests that one of these factors, either genetic or environmental, has a negative influence on the trait resulting in trait that is opposite to what is expected or desired
What is heritability?
Heritability is the proportion of the phenotypic variance of a trait contributed to by breeding value
Remeber breeding value is value of an individal as a genetic parent
What is the equation used to calculate the heritability of a trait?
h^2 = heritability
𝜎^2 BV = additive gene variance
𝜎^2 P = phenotypic variance
𝜎^2 GCV = gene combination variance
𝜎^2 E = envrionmental effect on phenotypic variance
Explain how this equation calculates the heritability of a trait
Heritability is the proportion of the phenotypic variance of a trait contributed to by breeding value. Breeding value is the genetic value of a parent for a specific trait, so by dividing the additive gene variance (BV) (which is the infleunce of individual genes on the phenotypic variance of a trait) by the phenotypic variance (P) (which can be infleunced by multiple factors including BV, GCV and E), we can estimate the genetic contribution i.e. the breeding value to the phenotypic variance of a trait and this heritability
What are the three main approaches that can be used to predict an individuals breeding value?
Individuals own performance records
Performance records of ancestors and/or collateral relatives (i.e. pedigree data)
Performance records of desendents of the individual (i.e. progeny data)
How can an individuals performance records be used to estimate the individuals breeding value?
Heritability x individuals observation - population mean
Breeding values represent the genetic value of an animal as a parent, and we can use an individuals performance records to calculate this. By multiplying heritability (which represents the genetic contribution to a specific trait) by the difference between the individual’s observation and the population mean, we can estimate the breeding value
If a bull has a 400 day daily liveweight gain that is 50kg better than the average bull within that population, and the heritability is 0.3, calculate the breeding value for this bull
Heritability x individuals observation - population mean
= 0.3 x 50
= 15kg
We would expect then, that the progeny of this bull would gain 7.5kg more than the average for that population. We divide the 15kg by two as the offspring will only inherit rougly 50% of their genes from the sire, and the other 50% from the dam
What is the difference between linkage equilibrium and linkage disequilibrium?
Linkage equilibrium and linkage disequilibrium are terms used to describe the relationship between alleles at different loci on a chromosome. Linkage equilibrium describes alleles at different loci that are inherited independently of each other. Linkage disequilibrium describes certain combinations of alleles at different loci that are inherited together more than expected, but by chance
When are alleles more likely to exhibit linkage disequilibrium?
When the genes carrying these alleles are physically close to one another on the chromosome as there will be less opportunities for the formation of a chiastama between the alleles and thus independent segregation of these alleles
What is the equation used to calculate the probability of linkage equilibrium between two alleles (A and B)?
PAB = PA·PB
PAB = probability of linkage equilibrium between A and B
What is the equation used to calculate the probability of linkage disequilibrium between two alleles (A and B)?
DAB = PAB - PA·PB
DAB = linkage disequilibrium between two alleles
What are genome wide association studies (GWAS)?
Genome wide association studies (GWAS) are research studies used to investigate the relationship between genetic variation and specific traits within a population
Describe how genome wide assciation studies (GWAS) are carried out?
In a genome wide association study (GWAS), animals within a population are genotyped for multiple genetic markers and their phenotypic values are measured. Analysing the releationship between the genotypes and phenotypes allows for the use of statistical tests, such as t-statistics and p-values, to determine if there is a significant association between genetic variations and observed phenotypes
When are genetic variations considered to have a significant association with an observed phenotype in a genome wide association study (GWAS)?
If p < 10^(-7)
What is genomic selection?
Genomic selection is a breeding technique where additively combining the phenotypic predictions from individual genotypes is used to provide an overall prediction for phenotype for each of several traits
In which industry is genomic selection most commonly used?
Dairy cattle industry
