Week 2 Flashcards
What was the proportion of tall pea plants to small pea plants that Mendal found?
787:277
2.84:1
Tall peas : dwarf plants
What is the ratio found in a dihybrid cross?
9 : 3 : 3 : 1
What is the phenotypic ration of partial dominance?
1 : 2 : 1
Why aren’t lower cases used in incomplete dominance?
As there is no clear dominance relationship, so the 2 alleles are denote as R1 and R2
What are the genotypic relationship between F2 generation snapdragon (Antirrhinum) where P1 has a red flower and white flower?
1 - red flower
2 - pink flowers
1 - white flowers
What is codominance?
Two alleles of a gene produce a distinct, detectable gene product and detectable effects on phenotypes
What is the difference between incomplete dominance and codominance?
Incomplete dominance they is no clear two products of genes having an impact, where codominace there is a clear example of both genes working.
What is the human MN blood group?
A red blood cell glycoprotein antigen existing in two forms M and N
Where is the human MN gene found?
MN gene controlled by autosomal (chromosome 4) locus (L)
What are the 3 potential expressions of the MN gene?
2 x L^M = M
L^M x L^N = MN
2 x L^N = N
Whay s the ratio of the MN gene?
1/4 M and 1/4 N
1/2 MN
What are the 4 blood types and what are there antigens and antibodies?
Blood type : Antigen : Antibody
A : A : anti-B
B : B : anti-A
AB : A+B : neither
O : neither : anti-A and anti-B
What is the relationship between the 3 blood genes?
A and B are codominant but both are dominant to O
How are the 3 blood types written out as genes?
I^A
I^B
I^O
What is the presubstance to the antigens to blood types and what does it contain?
H substance
Fucose – Galactose – AcGluNH (N-acetyl galactosamine)
What allows for fucose to the H substance precursor?
FUT 1 allele
What does I^A do?
I^A directs the addition of N-acetylgalactosamine to H substance
What does I^B do?
I^B directs the addition of galactose to the H substance?
What does I^O do?
I^O does nothing do the final antigen is just the H substance
What happens if there is a mutation that abolish the function of a essential gene?
The mutations are lethal to embryos
What is the genotype of the survivors of recessive lethals mutations?
1:2
Homozygous Dominant : Hetrozygous
What is the genes involved in mouse coat colour?
AA - agouti
AA^Y - Yellow
A^YA^Y- Lethal
Which is dominant A or A^Y in mice?
A^Y is dominant in terms of cout colour but A is dominant in terms of survival
What are the end result of domiant lethal alleles?
They are usually lost from the population as they can’t be maintained in a heterozygous state except in cases of late onset
What are the genes of Huntington diseases?
HH - individuals exhibit early onset
Hh - individuals often exhibit late onset (40<) so chance gene can pass on to the mutant gene to children
What is epistasis?
One gene pair masks or modifies the expression of another gene
What were the type of genes that Mendel investigated?
Discontinuous (discrete i.e all or nothing)
What is gene interaction?
More than one protein maybe required for developement of a single phenotype
Who is the Bombay women?
She is a women from Bombay indicated she must carry I^B allele but phenotypically was blood group O
What was the mutation that the Bombay women had?
She had a mutation in the fut1 allele which prevented the formation of complete H substance therefore supressing A and B antigen production
What is the relationship between fut1 gene to I^A and I^B
The fut1 gene is epistatic to the I^A and I^B gene
What happens to the Bombay women with the H substance?
As the group isnt produced so she produces anti-H antigen antibodies. This makes her at risk for getting haemolytic transfusion if they blood group O blood.
What does the ‘I’ mean in blood types?
Isoglutinogen
What is duplicate recessive epistasis?
When the recessiveness of two genes can impact the expression of phenotype
How does duplicate ressive epistasis impact the flower colour of Sweat Peas?
Hetrozygous or Homozygous domiant for both genes are required for the leaves to be purple
What happens in sweat peas if the ‘a’ gene is homozygous recessive?
The precursor substance is unable to be converted to the intermediate substance
What happens in sweat peas if the ‘b’ gene is homozygous recessive?
The precursor substances can be converted into the intermediate substance but can’t them be converted into the final product so the flower stays white
What is the ratio of purple sweat pea flowers to white flowers?
9 purple to 7 white
7 white can be broken down into 3 A_bb : 3 aaB_ : aabb
What is the phenotype ratio of F2 Drosophila melanogaster eye colour where the first generation is brown x scarlet and F2 is wildtype?
9 wild type (brick red colour)
3 brown
3 scarlet
1 white
What genes are working in order for the wild type eye colour in Drosophilia melanogaster?
Both the brown and scarlet genes are working allowing for the production of drosopterin and xanthommatin
What is needed for the eye colour of Drosophilia melanogaster to be scarlet?
The flies have the 2 recessive scarlet genes meaning they do not make xanthommatin so dont produce any brown pigment
What is needed for the eye colour of Drosophilia melanogaster to be brown?
The flies have to have 2 recessive brown genes meaning drosopterin so do not produce any scarlet pigment
What is needed for the eye colour of Drosophilia melanogaster to be white?
The fly needs to be homozygous resessive in both brown and scarlet meaning neither xanthommatin or drosopterin are produced
What are the phenotypes of F1 Dosophilia when the mother has wildtype eyes and father has white eyes?
All the males and females have wildtype eyes
When the F1 Dosophilia, mother WT and father White, reproduce what is the phenotype of their childrens eyes?
All the female eyes are wildtype
Half of the male eyes are wildtype
Half of male eyes are white
What are the phenotypes of F1 Dosophilia when the mother has white eyes and father has wildtype eyes?
All the female eyes are wild type
All the male eyes are white
When the F1 Dosophilia, mother white and father wildtype, reproduce what is the phenotype of their childrens eyes?
Half females have red eyes
Half females have white eyes
Half male have red eyes
Half males have white eyes
What is the term used used to describe males in x linkage?
‘hemizygous’ as they only have 1 x chromosome so cant be homozygous and heterozygous
What is gene drive?
The function is to cause non-Mendelian inheritance patterns and the rapid spread of transgenes through a population
What is the purpose of gene drive?
Designed with payloads (genes) that cause desired traits
What is the current method for gene drive?
CRISPR-Cas9
What does CRISPR stand for?
Clustered Regularly Interspaced Short Palindromic Repeats
What does Cas9 stand for?
CRISPR associated protein 9
What does gRNA mean?
Guide RNA
What is the first stage of gene drive?
Guide RNA guides Cas9 to the section of DNA which allows Cas9 to cut the DNA. Then the Cas9 and gRNA are inserted into the DNA with any DNA inbetween
What is the second stage of gene drive?
Homologous Directed Repair fixes the DNA strand building the DNA of the Cas9 and gRNA to complete the other strand
Does gene grive only impact 1 allele?
No the second allele is also rebuilt as the first allele will code for cas9, gRNA and any DNA inbetween which then inserts itself into the other allele
Will gene drive impact future generations?
Theoretically yes as the children will inherit 1 mutated allele which will then insert itself into the other gene. This will repeat across all future generations
What are 3 examples of genes that can be inserted to reduce mosquito (Anopheles stephensi) related infection?
Altered Akt - increase signalling response to human blood insulin and reduced Plasmidium falciparum infection by 66-99%
Anti-P. falciparum circumsporozoite protein (PfCSP) single-chain antibody (scFv) reduce parasite transmission of parasite to mice from 83% to 25%
Two single-chain antibodies (scFv) that target pathogen circumsprozoite protein and chitinase. Using gene drive this was introgressed into ~99.5% of the progeny
How can genes be resistant to CRISPR induced cleavage?
The cleavage is repaired by non-homologous end-joining (NHEJ). This means that mutated sites are no longer recognised by the drives gRNA
How have scientists overcome the resistance challenges by non-homologous repair?
They target the Anopheles gambia doublesex (dsx) gene
What happens when the doublesex gene is targetted?
Males are normal but females are sterile
No resistance observed
In caged population, proportion of modified individuals increased and modified egg production reduced progressively from one generation to the next
Total population collapse
What is molecular genetics?
The study of how differences in the structure (or expression) of DNA manifests as phenotype variations in organisms
What are the core field mergings in molecular genetics?
Medelian inheritance, molecular biology and biotechnology
What is the aim of molecular genetics?
Link gene sequences to phenotypes/ link mutations to genetic conditions
What is the central dogma of molecular biology?
The process by which instructions in DNA are converted into a functional product.
Who and when was this central dogma first proposed?
Francis Crick in 1958
What does the central dogma suggest?
That DNA contains the informations needed to make all of our proteins, and that RNA is a messenger that carries this information to the ribosome
What happens with a mutation in the enhancer?
Reduction or increase in amount of gene product
What happens with a mutation in the promoter?
Reduction or increase in amount of gene product
What happens with a mutation in the start codon?
Abolition of translation or aberrant translation
What happens with a mutation in the exon donor consensus or the exon acceptor consensus?
Aberrant splicing - non functional protein
What happens with a mutation in the stop codon?
Failure of translation termination - carboxy terminal extension of protein
What happens with a mutation in the Poly(A) addition signal?
Failure of polyadenylation - reduced mRNA stability and reduced protein
Why molecular genetics important?
Studies structure and function of gene at molecular level - allows us to combine patterns of inheritance with studies of gene structure to understand molecular function
What is the advantage of molecular genetics over classical genetics?
Classical genetics requires a phenotype. Not all allelic variation produces a phentotype and phentypes can be affected by envrionement.
Molecular genetics can identify and track subtle sequence differences
What is the phenotypic ratio for two heterozygous parents?
3:1 (Dominant trait: Recessive trait)
What is the genotypic ratio for two heterozygous parents?
1:2:1 (Homozygous dominant: Heterozygous: Homozygous recessive)
What allows for Restriction Fragment length Polymorphism?
Sequence variation creates unique sites for restriction endonucleases e.g. EcoRI
When was Restriction Fragment length Polymorphism invented?
1984
What 2 processes after introduction of restriction enzymes are used?
Gel electrophoresis and southern blot
What were the early uses of Restriction Fragment length Polymorphism?
Genome mapping
Indentifying genetic disorders
Paternity testing
What are the problems of Restriction Fragment length Polymorphism?
Large amounts of DNA
Probe label design
Length Southern Blot procedure
Is Restriction Fragment length Polymorphism used today?
Largely obsolete due to increasily inexpensive DNA sequencing
What is PCR?
Polymerase Chain reaction allowing for the genotyping of individuals and loci
How does PCR work?
Extract whole DNA
Produce an ‘amplicon’ region of targeted amplification using primers
What are the 3 stages of PCR and their temperatures?
Denaturing stage= 94-95 degrees C
Annealing stage= 50-56 degrees C
Extending stage= 72 degrees C
Why is restriction digest of PCR amplicons more effective than Restriction Fragment length Polymorphism?
Much faster due to PCR creating many copies of the gene that needs to be targeted
What is the downside of restriction digest of PCR?
Still need a mutation to have introduced a recognition site
How can PCR products be determined without restriction enzymes?
The change in size of PCR products on a gel electrophoresis
What is the first step of sanger sequencing?
PCR with fluorescent chain-terminating ddNTPs
What is the second step of sanger sequencing?
Size seperation by capillary gel electrophoresis
What is third step of sanger sequencing?
Laser excitation and detection by sequencing machine
In a output chromatogram in sanger sequencing what does a larger peak mean?
The confidence in result
How is Sanger sequencing important for PCR?
Sanger sequencing is a downstream method for PCR results
What is the steps in whole genome sequencing for the reference gene ie Human Genome Project?
Break genome into larger fragments
Order clones
Break individual clones into small pieces
Generate thousands of sequence reads and assemble sequence of clone
Assemble sequence reads of overlapping clones to establish reference sequence
What are the steps for generating a persons genome sequence?
Break genome into small pieces
Generate millions of sequence reads
Align sequence reads to established reference sequence
Deduce starting sequence and identify differences from reference sequence
What is the size and frequency (1 per x kb) of SNP mutation?
1bp
1 per 1kb
What is the size and frequency (1 per x kb) of InDel?
1-100bp
1 per 10kp
What is the size and frequency (1 per x kb) of SSR?
1-10bp
1 per 30kp
What is the size and frequency (1 per x kb) of CNV?
10bp-1Mb
1 per 60 kb
What is the size and frequency (1 per x kb) of Inversions?
1bp> 1Mb
1 per ?
What is SNP?
Single Nucleotide Polymorphism
What can SNP affect?
mRNA stability
Promoter activity
Peptide formation
What are InDel?
Insertion or deletion of a single stretch of DNA sequence (2nd most common)
What commonaly causes InDel mutations?
DNA replication or DNA repair (NHEJ)
What is SSR?
Simple Sequence Repeat
Sequence of one to a few bases that repeat in tandem form <10 times to >100 times
What are SSR with larger repeating units?
Are less frequent and will be classified as Copy Number Variants (CNVs)
What is the cause of Huntintons disease?
The more SSR regions the more severe the symptoms ie 20-30 no conditions, 50-99 late onset and 100 or more early-onset disease, the more repeats the earlier the symptoms
How can genotyping help with determining if a person has sickle cell disease?
As it is caused by a single nucleotide changing from an A to a T (it is homozygous recessive)
How can gene editing help cure Sickle cell disease?
Use lentivirus to code for normal beta-globin gene
Use CRISPR to inactivate the inhibitor for y-globlin- alternative to beta-globin but only during fetal development
Use CRISPR to swap the mutated beta-globin gene for the normal sequence fully repairing the sickle cell mutation
