Genes L11 Notes Flashcards
Give an example of interactions between genes
Coat colour -> mammals
List the Genes controlling coat colour in mammals & what they control
A gene: >> Distribution of pigment -> hair strands B gene: >>Colour of pigment C gene: >>Colour expression W gene: >> Distribution of pigment -> overall coat
Describe what the A gene involved in controlling coat colour is in charge of & describe it’s different alleles.
A gene: >> Distribution of pigment -> hair strands Allele (A): Agouti -> Lighter hair in middle Allele (a): Solid black
Describe what the B gene involved in controlling coat colour is in charge of & describe it’s different alleles.
B gene: >>Colour of pigment Allele (B): Black Allele (b): Cinnamon
Describe what the C gene involved in controlling coat colour is in charge of & describe it’s different alleles.
C gene: >>Colour expression Allele (C): Colour expressed Allele (c): Albino -> colour not expressed.
Describe what the W gene involved in controlling coat colour is in charge of & describe it’s different alleles.
W gene: >> Distribution of pigment -> overall coat Allele (W): Dominant white / white spotting Allele (w): Even distribution
What is epistasis?
• Epistasis:
Interaction between 2 or more genes controlling a single genotype.
Allele of one gene masks phenotypic effect of allele of another gene
Used to dissect biochemical & developmental pathways.
Name the two types of epistasis & their associated phenotypic ratios.
Recessive -> 9:4:3
Dominant -> 12:3:1
Describe how recessive epistasis occurs using an example
• Recessive epistasis:
9:4:3 phenotypic ratio
Eg. Parental Phenotypes: Cinnamon x Albino
Genotypes: bb CC x BB cc
100% Agouti offspring (WT)
Offspring F1 Phenotypes: Agouti x Agouti Genotypes: Bb Cc x Bb Cc 9 Agouti -> B_C_ 3 Albino -> B_cc 3 Cinnamon -> bbC_ 1 Albino -> bbcc Phenotypes: 9:4:3 9 Agouti : 4 Albino : 3 Cinnamon Instead of normal 9:3:3:1 ratio.
Describe how dominant epistasis occurs using an example
• Dominant Epistasis:
12:3:1 Phenotypic Ratio
Eg. Parental Phenotypes: White x Cinnamon
Genotypes: WW BB x ww bb
100% White offspring (Ww Bb)
Offspring F1 Phenotypes: White x White Genotypes: Ww Bb x Ww Bb 9 White -> W_B_ 3 White -> W_bb 3 Agouti -> wwB_ 1 Cinnamon -> wwbb Phenotypes: 12:3:1 12 White : 3 Agouti : 1 Cinnamon Instead of normal 9:3:3:1 ratio.
Describe the characteristics of the albino allele of coat colour
• Albino allele: Epistatic -> all coat colour genes Mutation Recessive Loss of function Enzyme tyrosinase -> melanin synthesis -> melanocytes > Tyrosine -> Tyrosinase >>Eumelanin (Black) >>Pheomelanin (Yellow)
Name the two types of melanin / melanocytes of coat colour produced by tyrosinase
>
Tyrosine -> Tyrosinase >Eumelanin (Black) >Pheomelanin (Yellow)
Describe dominant white / white spotting
• Dominant White / White Spotting
Epistatic -> all coat colour genes (except albino)
Mutation
Dominant
Loss of function
Transmembrane growth factor receptor (c-kit) -> proliferation (division) &
migration -> melanocytes
»_space; ww melanocytes -> Active growth factor receptor (dimer)
-> Proliferation & migration
»_space; Ww melanocytes -> Inactive growth factor receptor (dimer)
-> No proliferation & migration.
Name the two types of melanocytes involved in transmembrane growth factor receptors & describe their characteristics
Transmembrane growth factor receptor (c-kit) -> proliferation (division) &
migration -> melanocytes
»_space; ww melanocytes -> Active growth factor receptor (dimer)
-> Proliferation & migration
»_space; Ww melanocytes -> Inactive growth factor receptor (dimer)
-> No proliferation & migration.
Describe the characteristics of ww melanoctytes
> > ww melanocytes -> Active growth factor receptor (dimer)
-> Proliferation & migration
Describe the characteristics of Ww melanoctytes
> > Ww melanocytes -> Inactive growth factor receptor (dimer)
-> No proliferation & migration.
What is phenotypic variation?
Phenotypic variation -> Individuals w/ same phenotype but different alleles/genetic seq.
What is penetrance? Give an example
• Penetrance:
Measures % of individuals with a given phenotype -> express expected phenotype
Incomplete penetrance
Eg. Breast cancer susceptibility (BRCA genes)
What is expressivity? Give an example.
• Expressivity:
Measures extent of expression -> given genotype at phenotypic level.
Variable expressivity
Eg. Agouti viable yellow
–> Insertion -> transposable element -> promoter region of agouti gene
Name & describe the measures of phenotypic variation, including examples.
• Penetrance:
Measures % of individuals with a given phenotype -> express expected phenotype
• Expressivity:
Measures extent of expression -> given genotype at phenotypic level.
Incomplete penetrance Eg. Breast cancer susceptibility (BRCA genes) Variable expressivity Eg. Agouti viable yellow --> Insertion -> transposable element -> promoter region of agouti gene Incomplete penetrance & variable expressivity
Describe modifier genes & their consequences using examples
• Modifier genes:
Genetic interactions
Eg. Retinitis pigmentosa
Double heterozygosity -> mutations in PRPH2 & ROM1 genes
»_space; +/PRPH2- -> No phenotype
»_space; +/ROM1- -> No phenotype
Digenic inheritance
»_space; +/PRPH2- & +/ROM1- -> Retinitis pigmentosa
2nd Hit required:
»_space; 2 hit hypothesis -> familial cancer syndromes -> tumour suppressor genes
>Both alleles of tumour suppressor gene
-> must be inactivated for tumour formation (loss -> heterozygosity)
Eg.
»_space; Neurofibromatosis Type 1 (peripheral nervous system)
- Dominant familial cancer syndrome
- 1/3500
- Benign neurofibromas under skin & ‘Café au lait’ spotting -> skin
- Very varied severity
Pearson Twins -> Facial tissue cells -> Adam -> homozygous -> NF1 mutation
-> Neil -> heterozygous
Loss of heterozygosity -> Adam -> during foetal dev. -> Cell
lineage forming face.
CT scans -> tumors -> Neils abdomen -> asymptomatic.
> > Retinoblastoma (Retina)
BRCA1/2 (breast & ovary)
Give an example of genetic interactions as a result of modifier genes
• Modifier genes: Genetic interactions Eg. Retinitis pigmentosa Double heterozygosity -> mutations in PRPH2 & ROM1 genes >> +/PRPH2- -> No phenotype >> +/ROM1- -> No phenotype Digenic inheritance >> +/PRPH2- & +/ROM1- -> Retinitis pigmentosa
What is the 2nd hit hypothesis regrading modifier genes?
2nd Hit required:
»_space; 2 hit hypothesis -> familial cancer syndromes -> tumour suppressor genes
>Both alleles of tumour suppressor gene
-> must be inactivated for tumour formation (loss -> heterozygosity)
Explain/describe the 2 hit hypothesis of modifier genes using examples
2nd Hit required:
»_space; 2 hit hypothesis -> familial cancer syndromes -> tumour suppressor genes
>Both alleles of tumour suppressor gene
-> must be inactivated for tumour formation (loss -> heterozygosity)
Eg.
»_space; Neurofibromatosis Type 1 (peripheral nervous system)
- Dominant familial cancer syndrome
- 1/3500
- Benign neurofibromas under skin & ‘Café au lait’ spotting -> skin
- Very varied severity
Pearson Twins -> Facial tissue cells -> Adam -> homozygous -> NF1 mutation
-> Neil -> heterozygous
Loss of heterozygosity -> Adam -> during foetal dev. -> Cell
lineage forming face.
CT scans -> tumors -> Neils abdomen -> asymptomatic.
> > Retinoblastoma (Retina)
BRCA1/2 (breast & ovary)
What is epigenetics?
• Epigenetics:
Inherited changes in gene function -> not caused by mutation
Describe epigenetic regulation of gene expression
• Epigenetic regulation -> Gene expression
Environmental factor -> switches on expression -> red & green genes
-»Expression
> Green gene -> transient (a)
-> not expressed -> daughter cells
> Red gene -> persistant (b)
-> expressed along multiple cell divisions / generations
-»Epigenetic effect.
Describe the role of the green gene in epigenetic regulation of gene expression
> Green gene -> transient (a)
-> not expressed -> daughter cells
Describe the role of the red gene in epigenetic regulation of gene expression
> Red gene -> persistant (b)
- > expressed along multiple cell divisions / generations - >>Epigenetic effect.
What are epigenetic tags?
• Epigenetic tags:
DNA methylation & histone modifications
>Alter chromatin structure
–>passed to daughter cells.
What is genomic imprinting?
Describe both paternal and maternal genomic imprinting.
• Genomic imprinting:
- Paternal:
Paternal allele imprinted & silenced ->By epigenetic tags
Maternal allele preferentially expressed -> embryo
- Maternal:
Maternal allele imprinted & silenced ->By epigenetic tags
Paternal allele preferentially expressed -> embryo
Describe paternal genomic imprinting
- Paternal:
Paternal allele imprinted & silenced ->***By epigenetic tags
Maternal allele preferentially expressed -> embryo
Describe maternal genomic imprinting
- Maternal:
Maternal allele imprinted & silenced ->***By epigenetic tags
Paternal allele preferentially expressed -> embryo
Give an example of genomic imprinting & describe
Eg. lgf2 gene: Insulin-growth-like-factor 2 >>Required -> normal growth >>Only paternal copy of gene expressed >>Maternal copy of gene silenced & imprinted
Both mice heterozygous for recessive lgf2 mutant allele >Mouse -> Mutant allele inherited -> mother -> Normal size Maternal genomic imprinting >Mouse -> Mutant allele inherited -> father -> Dwarf size Paternal genomic imprinting >>Parent of origin effect
Describe maternal genomic imprinting using an example.
Both mice heterozygous for recessive lgf2 mutant allele
>Mouse -> Mutant allele inherited -> mother -> Normal size
Maternal genomic imprinting
Describe paternal genomic imprinting using an example.
Both mice heterozygous for recessive lgf2 mutant allele
>Mouse -> Mutant allele inherited -> father -> Dwarf size
Paternal genomic imprinting
What is the parent of origin effect? Give an example
• Parent of origin effect:
When the phenotypic effect of an allele depends on whether it is inherited from the mother or father.
Eg. Igf2 gene
Describe the affect of genomic imprinting on growth
Affects limited no. genes (100 -> mouse)
Many imprinted genes -> involved -> foetal growth
Paternally expressed genes -> promote growth
Maternally expressed genes -> suppress growth
Describe the effect of paternally expressed genomic imprinted genes on growth
Paternally expressed genes -> promote growth
Describe the effect of maternally expressed genomic imprinted genes on growth
Maternally expressed genes -> suppress growth
Describe the parental conflict / kinship theory
***–»> Kinship / Parental conflict theory:
Conflict between sexual / reproductive interests -> maternal &
paternal genes in foetus.
»_space; Mother -> equally related to all offspring
>Wants to divide resources equally
»_space; Father -> likely related to subset of foetuses
>Wants to incr. survival chances of his offspring -> promoting
their growth.
Describe the mother’s stance in the kinship/parental conflict theory
> > Mother -> equally related to all offspring
>Wants to divide resources equally
Describe the father’s stance in the kinship/parental conflict theory
> > Father -> likely related to subset of foetuses
>Wants to incr. survival chances of his offspring -> promoting
their growth.
What is the parental conflict/kinship theory?
***–»> Kinship / Parental conflict theory:
Conflict between sexual / reproductive interests -> maternal &
paternal genes in foetus.