Genomics and inheritance

genotype

genetic material inherited from parent

How many copies of each gene does an individual have?

2 (one from each parent) - EXCEPT on x or y chromosome

What is the expressed phenotype of cells/organisms influenced by?

genotype

inherited epigenetic factors

non-inherited environmental factors

What do alterations to the genetic code have a potential to do to a specific protein?

• increase

• modify

• stop production

Are consequences of alterations to coding or non-coding sequence easier to predict?

coding sequence

Does dominance indicate whether an allele is beneficial, detrimental or neutral?

NO

What does the dominant alleles usually produce?

functional protein

Dominant allele

• only one copy required to affect phenotype

• complete or partial (incomplete)

Recessive allele

2 recessive copies required to affect phenotype

What does it mean for alleles to be ‘co-dominant’?

both alleles manifest at the same time as eachother

What can cause DNA alterations?

• physical or chemical damage

• replication going wrong during mitosis & meiosis

• somatic cell errors not being repaired leading to dysplasia or neoplasia

• errors within gametes or embryonic cells lead to novel characteristic

What does chromosomal separation during mitosis and meiosis result in?

• altered structures of chromosomes

• movement of long sections of DNA or their inversion

What is munchkin deformity caused by?

dominant, lethal gene with variable penetration

What does bully whippet appearance occur due to?

• 2-bp deletion in myostatic gene located on canine chromosome 37

• monozygous affected dogs look like this - too much muscle, end up with lots of muscle damage due to inability to get oxygen

What does this image show?

belgian blue cattle - excessive muscles

What causes hypertrophic cardiomyopathy in Maine Coon cats?

missense mutation in cardiac myosin binding protein C

What are the steps in genome mapping in animals?

• identify gene(s) responsible for genetic trait of economic or clinical importance

• marker-assisted selection

What can we use identifying gene(s) responsible for genetic trait of economic or clinical importance for?

• model for human disease

• map genes in animal pedigrees

• eliminate affected individuals and carriers from gene pool

What is marker-assisted selection used in?

• conventional breeding programmes to increase frequency of desirable traits

• introgression of genetic material from one population to another

What technique is used for DNA sequencing?

Sanger technique

What are reactions containing individual ddNTPs run on in the sanger technique?

• gel

• labelled with different fluorophores

What are the methods used for DNA sequencing?

• sanger sequencing

• pyrosequencing

What are single nucleotide polymorphisms (SNPs)?

any single position within the genome sequence where nucleotide differences may occur

What can the presence of single nucleotide polymorphisms (SNPs) be used as?

linkage markers for the presence of nearby genes controlling traits of interest (because these differences are passed down generations)

How are SNPs analysed?

hybridisation of SNP alleles and detection using fluorescence

What are the applications of SNP-array analysis?

• genome-wide association studies (GWAS) enabled selection

• identification of quantitative trait loci

• evaluation of genetic merit of individuals

• comparative genetic studies

What is an example of an applications of SNP-array analysis?

sensory neuropathy in border collie

What are the types of point mutations?

• insertion

• deletion

• substitution of base pairs

What can alteration of the exonic sequence result in?

• silent

• missense

• nonsense

• frame shift

silent mutation

no change in aa sequence

missense mutations

a different aa is encoded

nonsense mutations

a premature stop codon is introduced

frame shift mutation

change in aa sequence from that point on

What can alteration of the intronic sequence result in?

• no changes

• altered splicing sites → change in aa sequence

• altered gene expression (increased or decreased)

exonic sequence

coding

intronic sequence

non-coding

What are the characteristics of autosomal dominant defects

• dominant

• defect seen in every generation

• every affected patient has at least one affected parent

• normal offspring from affected parents will produce normal offspring

• equal numbers of male and females will be affected

What are 2 examples of autosomal dominant defects?

• feline polycystic kidney disease

• Scottish fold osteodystrophy

What are the characteristics of autosomal recessive variance?

• defect may skip a generation

• all offspring of affected parents will be affected

• ‘normal’ parents of an affected individual must be a carrier

• equal numbers of male and female affected

Name examples of autosomal recessive traits

• hyperuricosuria in dalmatian dogs

• Avermectin sensitivity in collie dogs

What are the characteristics of X-linked dominance variance?

• every affected offspring has at least one affected parent

• affected males mated to normal females will transmit the defect to all their daughters and none of their suns

• unless defect common (affected female will be heterozygous and when mated to normal male the defect will be transmitted to half the offspring

Name an example of an x-linked dominant trait

X-linked dominant hereditary nephritis in Samoyed

What are the characteristics of x-linked recessive variance?

• may ‘skip a generation’

• incidence in male > female

• when defect rare: affected individuals will be males and will have in inherited the gene from the dam

Name an example of X-linked recessive traits

• Haemophilia A (factor VIII deficiency) in Havanese dogs

• more likely to see this in cocker spaniels but cause unknown

genotype

organism’s full hereditary information

phenotype

actual observed properties

Heritability of the characteristic =

proportion of the phenotypic variation that is due to genotypic variation

What can heritability be predicted by?

analysis of population statistics

What are some examples of heritability?

• reproduction (dairy cattle,pigs) LOW

• 305-day lactation yield (dairy cattle) MODERATE

• milk composition % (dairy cattle) HIGH

• carcass fat depth (pigs) MODERATE

Why is heritability important?

how easy able to select for characteristics

List methods of selection

• performance test

• pedigree analysis and ancestor evaluation

• progeny testing

• performance of siblings

• marker assisted selection

• calculations (e.g. estimated breeding value, true breeding value, selection intensity)

performance test

selection of basis of phenotype

Name an example of where performance testing occurs

black vs red aberdeen angus

What are the limitations of performance testing?

• phenotype may not reflect genotype

• only effective for high heritability characteristics

• if autosomal recessive trait select against - recessive allele cannot be eliminated due to presence of carriers

Pedigree analysis/ancestor evaluation

based off records of ancestors

What is using pedigree analysis/ancestor evaluation useful for?

late manifesting traits, where parental records are the only indication of a young animal’s potential performance

Progeny testing

look at performance of offspring to determine valuability of that individual

How can you look at the performance of the offspring in progeny testing?

• assessing non-additive gene effects

• assessing low heritability characteristics

• assessing sex-limited characteristics

• assessing carriers of a recessive gene

What is progeny useful for?

where semen is banked, e.g. Holstein cattle

What characteristics is assessing the performance of siblings useful for?

characteristics that cannot be seen and assessed on the live individual

What is marker assisted selection (in cattle) used for?

bulls used in artificial insemination across several different herds

What is marker assisted selection/ best linear unbiased prediction (BLUP) in cattle?

a number of marker sites have been mapped in the bovine genome with loci (QTLs) linked to certain production rates

What was marker assisted selection/ best linear unbiased prediction (BLUP) in cattle originally developed for?

selection using phenotypic data

genetic gain is greater the _______ the selection intensity

greater

What impacts selection intensity?

• males > female

• larger population = greater possible selection intensity

What factors affect the rate of improvement?

• heritability of trait

• intensity of selection

• generation interval

• number of traits required for improvement

What methods are available for selection of more than one trait?

• tandem selection

• independent culling

• selection index-marker assisted selection

What method for selection for more than one trait does this graph show?

tandem culling

What method for selection for more than one trait does this graph show?

independent culling