Vet Genetics Exam II

Are identical twins considered clones?

True

Which epigenetic mechanisms contribute to phenotypic differences between identical twins?

DNA methylation, histone modifications, non-coding RNAs

What causes the coat color to change from yellow to brown?

Diet rich in methyl groups fed to pregnant mothers

Do DNA methylation patterns in identical twins remain identical throughout life?

False

How does epigenetic therapy work?

Changing instructions of the cancer cells using epigenetic drugs that add or remove epigenetic marks

How does DNA methylation contribute to AMR, particularly through the restriction modification (R-M) system?

DNA methylation protects bacterial DNA from restriction enzymes and regulates gene expression. R-M systems methylate specific sequences, allowing bacteria to distinguish self from foreign DNA. This influences AMR because methylation patterns determine whether plasmids carrying resistance genes are degraded or maintained. Some plasmids escape restriction by carrying their own methylases, enabling the spread of AMR genes.

How do nucleoid-associated proteins (NAPs) act as histone-like regulators of AMR?

Bacterial genomes are packed into nucleoids through nucleoid-associated proteins (NAPs) in distinct cytoplasmic regions, rather than having a membrane-bound nucleus like eukaryotic cells. NAPs compact bacterial DNA and regulate transcription similarly to eukaryotic histones. They influence AMR by controlling virulence genes, efflux pumps, stress responses and biofilm formation.

How do non-coding RNAs (ncRNAs) regulate AMR?

ncRNAs bind mRNAs to suppress or activate translation — could reduce antibiotic entry or activate translation of another gene by preventing inhibitory mRNA structures, promoting certain biofilm formation and virulence - these regulatory RNAs modulate membrane permeability, efflux, and stress response (which influence AMR)

Epigenetics

heritable changes in gene expression without changing DNA sequence (same genome, different phenotypes due to regulation) - translates environmental signals to phenotypes

Genetic plasticity: sex determination in alligators and sea turtles

An example of epigenetics in which the sex of alligators is determined by egg incubation temperature (warmer = 100% female)

DNA methylation

The addition of -CH3 to cytosine (DNA) at CPG sites), for gene silencing and activation. Blocks transcription factor binding or recruits repressors

Histone modification

DNA is packaged by histones into chromosomes. Modification of these histones allows an increase or decrease in the transcription of genes within these sequences of DNA.

Acetylation in histone modification (HATs)

the addition of an acetyl group (negatively charged) to a histone chromatin (negatively charged DNA) to open the chromatin and increase transcription

Deacetylation in histone modification (HDACs)

the removal of acetyl groups from chromatin, closing the chromatin and decreasing transcription of the DNA sequence involved

Non-coding RNAs (ncRNAs)

including miRNA, siRNA - post transcriptional regulation that degrades mRNA or blocks translation

X-chromosome inactivation

(IN FEMALES) one X is randomly inactivated, forming a barr body - controlled by RNA

X-chromosome inactivation: calico cat example

coat color controlled by several genes, one gene located on chromosome X. One codes for orange, the other codes for black. Orange is dom to black, but if a calico is heterozygous, random X inactivation will result in calico coat

Epigenetic example: agouti mice

in agouti mice, an unmethylated gene resulted in the production of a yellow, obese, disease-prone offspring. The methylated gene resulted in a brown, healthy mouse. Diet can influence this.

Genomic imprinting

Gene expression depends on the parent of origin. Only one allele (maternal or paternal) is expressed, while the other is silenced epigenetically

Parental conflict theory

paternal genes promote growth at the expense of the mother, while maternal genes restrict growth for resource allocation and success for future litters

Establishment of genomic imprinting

established via DNA methylation and imprinting control regions

Mechanisms of genomic imprinting

Promoters/enhancers are epigenetically marked (induction of imprinting to some genes - regulate by binding to transcription factors) / Methylation (prevents transcription factor binding, shutting down expression)

DNA methyltransferase (DNMTs)

maintains DNA methylation after each DNA replication by using parental DNA strand as a template to methylate daughter strand

callipyge sheep (genomic imprinting example)

muscle hypertrophy, overly muscled rear, decreased muscle proteolysis (breakdown of protein into amino acids), due to polar overdominance and only expressed when mutation is inherited from the father

large offspring disorder (genomic imprinting example)

triggered by in-vitro fertilization, caused by epigenetic disregulation - embryos have a higher sensitivity to external stimuli in in vitro production, imprints established prior to implantation, many implanted genes control growth

Barker Hypothesis

fetal programming - early -life environment determines long-term health outcomes during adult life

Dutch famine (nutritional epigenomics example)

prenatal malnutrition → adult disease risk, epigenetic changes persisted into adulthood

Agouti mouse (nutritional epigenomics example)

Maternal diet affects offspring phenotype via methylation (supplementation of methyl donors to maternal diet during pregnancy = normal coat color and birth weight, less health issues)

Honeybee example (nutritional epigenomics)

Queen and worker bee have same genome, queen is fed royal jelly (with royalectin) which increases body size and ovary development, decreases development time)

mechanisms of nutritional genomics

DNA methylation (methyl donors like folate), histone modifications, gene expression patterns

Mechanisms of epigenetics in drug resistance

Genetic: mutations in drug targets, drug metabolism differences - epigenetic: changes in gene expression (drug transporters), tumor cells silencing drug-sensitive pathways / limiting cellular uptake, modification of drug target, inactivation of drug

MDR1 gene mutation

a gene mutation that prevents the removal of drugs from a cat or dog’s brain

Linkage disequilibrium

non-random association of alleles

Factors for a successful GWAS

Large sample size (less stratification), accurate phenotyping (distinct classes), high marker density, population structure control

Lessons from GWAS (why GWAS succeeds or fails to determine genetic susceptibility to certain diseases)

Large sample size is critical, accurate assessment of phenotype must be narrowly defined

Ovine Progressive Pneumonia

caused by ovine lentvirus infection, slow progression (2 years of age or greater), loss of body condition despite normal appetite, increased resp effort, firm udder, no cure. GWAS detected genetics of host susceptibility

sensitivity

proportion of patients with disease that test positive

specificity

proportion of patients without disease that test negative

Porcine Reproductive and Respiratory Syndrome (PRRS)

Reproductive problems in breeding animals, resp problems in growing animals, single strand RNA virus. Most economically important swine disease in the US. Results of GWAS: wild type allele less common (greater opportunity to improve populations by selection), wild type dominant, no need for homozygosity.

Bovine Respiratory Disease (BRD)

Common respiratory disease in cattle, most economically significant, variety of pathogens cause fever, loss of appetite, shallow breathing - GWAS scored calves for BRD, nonconclusive (too many factors)

SINE element

short interspersed nuclear element - repeated DNA sequence (retrotransposon)

micropthalmia

abnormal eye development

epistasis

expression of one gene is modified (marked, inhibited, suppressed) by expression of one or more genes

hypostatic

gene whose expression is masked/suppressed by the expression of another gene (the epistatic gene)

pleiotropy

one gene may affect multiple phenotypes

Tyrosine variants

heat sensitive genes that create color variation in cats

MC1R (E locus)

this locus frequently masks other loci, deals with eumelanin and pheomelanin, and controls red/yellow coloring (ee = red/yellow, E_ allows A locus to show instead)

ASIP (A locus)

locus that controls the coat pattern, dominance hierarchy: DY, SY, AG, BS, BB, a

K locus

locus that creates black, brindle or allows agouti coat pattern (dominance in that order)

D locus

dilution locus (recessive = coat color dilution)

B locus

locus that determines black or brown coat (BB = black, bb = brown)

white coat locus

dominance: solid color, irish spotting, piebald, all white