MCO Genetics Flashcards
Difference between genetics and genomics
- Genomics: Technology used to generate large data sets
- Genetics: Method of experimentation to understand cause and effect between genes
How long is human DNA in a cell
2 metres
3 parts to the chromosome stucture
- Telomeres
- Centromere
- Euchromatin
Karyotype definition
the number and visual Appearance of the chromosomes in the cell nuclei of an organism or species
What is a telomere
The end of the chromosome arm
What is a centromere
The region where the two sister chromatids are held together
What is a kinetochore
The protein complex on the chromosome where microtubules attached during cell division
What is euchromatin
Regions where you find lots of genes on the chromosome
What is heterochromatin
Regions found near the centromere, responsible for the structural movement of the chromosome. Doesn’t contain much DNA for expression.
What is a telocentric chromosome
Where the centromere is at the tip of the chromosome. There is only 1 arm.
What is acrocentric chromosome
Centromere is located near the end of the chromosome
What is a submetacentric chromosome
Where the centromere is quite not in the centre.
What is a metacentric chromosome
Where the centromere is in the centre of the chromosome.
What are the different length arms resulting from different centromere positions
- Short arms (p)
- Long arms (q)
Visual catalogue to provide notation on a chromosome
There are different bands produced by staining to provide notation
Genome sequencing
- Can locate a gene down to base pairs
- Each gene has a unique number
Mitosis
- Generate 2 identical daughter cells
- Diploid
- Used for multiplication, growth & tissue maintenance
Meiosis
- Four genetically distinct daughter cells
- Sexual reproduction, ‘shuffles the deck’
The cell cycle
- Interphase: G1, S, G2
- Cell division
What happens in interphase
Organelles and chromosomes replicate
Stages of mitosis
- Prophase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis
What happens in prophase
- Centrosome duplicates and begin to move to poles
- Chromosomes start condensing
- Nuclear membrane breaks down
- Spindle forms, extending from centrosomes and across cell
What happens in metaphase
- Centromere align on the metaphase plate.
- There is bipolar attachment
What happens in anaphase
Chromosomes migrate to opposite poles
What happens in telophase
- Chromosomes at poles
- Spindle disassembles
- Nuclear membrane reforms
What happens in cytokinesis
- Chromosomes decondense
- Cells divide
How are sister chromatids joined together
Joined together by cohesins which are broken down by separases
Meiosis stages
Meiosis 1 and meiosis 2
What happens in prophase 1
- DNA condenses
- Nuclear membrane breaks down
- Homologous chromosomes align & synaptonemal complex forms
- Chiasmata the exchange of segments in chromatids
- Spindle fibres form
- DNA fully condensed, synaptonemal complex breakdowns, & monopolar kinetochores attach chromosomes to spindle
What happens in metaphase 1
Kinetochores have aligned at the equator (metaphase plate)
What happens in anaphase 1
Monopolar attachment pulls homologous chromosomes to opposite poles
What happens in telophase 1
Diploid cell have formed
How has “shuffling the deck’ has occurred
- Independent assortment of parental chromosomes
- Crossing-over of chromosome arms
What happens in prophase 2, metaphase 2, and anaphase 2
Same but sister chromatids become chrosomes
Telophase 2
Four genetically distinct haploid cells
Differences in meiosis between male and females
Males: 4 gametes per meiosis
Females: 1 gamete meiosis
5 stages of prophase 1
- Leptotene
- Zygotene
- Pachytene
- Diplotene
- Diakinesis
What happens in leptotene
- Chromosomes start to condense & become visible
- Homolog pairing begins
- Double-strand DNA breaks are introduced (potential sites for crossing-over)
What happens in zygotene
- A synaptonemal complex begins to form between homologous pairs (Synapsis)
- Paired homologs now referred to as bivalents
What happens in pachytene
- Condensing of chromosomes continues
- Synaptonemal complex is complete
- Bivalents now have four sister chromatids (tetrads)
- Crossing-over is completed
What happens in diplotene
- Synaptonemal complex disassembles
- Each pair of sister chromatids begins to separate
- Chiasmata are visible regions of cross-over between non-sister chromatids
What happens in diakinesis
- Chromosomes repel each other
- Non-sister chromatids remain loosely associated via chiasmata
- Nuclear envelope disintegrates
- Monopolar attachment of chromosomes to spindle fibers
Function of synaptonemal complex
- Facilitates late stages of recombination
- Prevents homolg pairs from getting entangled
What is a univalent
An unpaired chromosome during prophase 1 of meiosis
Medel’s experimental method
- Assemble a robust experimental system
- Careful design and perform first experiment, and quantify results to generates lots of data
- Repeat same experiment with different starting material
- Analyse the collective data and derive predicted model
- Devise and execute experiments to test predictions
- Validate molecular basis of predicted gene(s)
First law of inheritance
Heredity is controlled by paired factors (alleles) that separate in gametes and are joined up in fertilisation
What did william bateson do
Applied mendelian genetics to animals
What did roland biffen do
Produced a wheat variety that contained resistance to yellow rust
What statistical test is used to validate genetics
Chi-squared
Different genetic models
- Drosophila: used for multicellular development
- Mice: for mammalian acquired immunity
- Pea plant: used by Mendel
Model for first law of inheritance
- Discrete trait
- Complete dominance
- Environmentally stable phenotype
What is the chromosome theory
Chromosomes are the unit of heredity
What is frequency of recombination
- The frequency that 2 genes are co-inherited. Depends on the physical distance between 2 genes.
- The smaller the frequency the closer they are physically
- The greater the frequency the further apart they are
- 0% tightly linked, or same gene
- 50% unlinked on different chromosomes or far apart
What is the linear model
Genes are ‘physically’ located in a linear manner along a chromosome
Units for recombination
1% recombination = 1 Map unit = 1 centiMorgan (cM)
What is positional cloning
To identify a gene based on the location on the chromosome
Stages of positional cloning
- Identify the genes location (locus) from a genome-wide search of linkage to markers.
- Sequence the DNA across the locus, in both wild type and mutant variants.
- Verify function of the causal gene
What is a molecular marker
A difference in DNA sequence (DNA polymorphism) between two individuals. This can be:
- Base pair differences
- Deletions/ insertions
- Segmental rearrangement, where sequence is inverted
2 methods to verify function of the gene
- Mutational analysis
Loss-of-function experiment, by mutating allele - Genetic transformation Gain-of-function experiment, transfer allele to see if they gain phenotype
When is artificial mutation used
Main source of genetic variation used for research in experiments
Natural variation
The main resource for translational genetics
What did Muriel Wheldale find
That multiple genes influence colour of the flower in snapdragons
3 different types of dominance
- Complete dominance
- Incomplete dominance
- Overdominance
What is complete dominance
- Homozygous dominant and hetrozygous show maximum expression.
- Homozygous recessive shows no expression
What is incomplete dominance
- Homozygous dominant shows maximum expression
- Hetrozygous shows shows intermediate expression
- Homozygous recessive show no expression
What is overdominance
- Homozygous dominant shows intermediate expression
- Hetrozygous shows maximum expression
- Homozygous recessive shows no expression
What is penetrance and what are the 2 types
- Penetrance measures the proportion of individuals in a population who carry a specific gene and express the related trait.
1. Full penetrance
2. Partial penetrance
What is full penetrance
- Homozygous dominant and hetrozygous show maximum expression.
- Homozygous recessive shows no expression
What is partial penetrance
- Homozygous dominant shows medium expression
- Hetrozygous shows shows weak expression
- Homozygous recessive show no expression
How can genotypes be affected by the environment
- Chemical environment: hormones may treat dwarfism for one type of mutation but not for another
- Temperature sensitive: different expression in different temperatures
- Cell type: the cell type determines which genes are switched on
What is redundancy
Two or more genes are performing the same function
What are complementary genes
The phenotype depends on both genes being functional.
Objective of genetic mapping
To see which genes underlie a phenotype based on DNA sequence variation
2 methods of genetic mapping
- Linkage mapping
2. Association mapping
What is linkage mapping
Mapping based of know parentage, that exhibit contrasting phenotype and are polymorphic in many DNA markers (genome-wide)
Pros of cons of linkage mapping
Pros:
- No question of dominance -Immortal lines
- Powerful data accumulation
- Reproducibility
- GxE experiments possible
- Inter-mating inbreds, to test genetic models
Cons:
-Finite resource
What does magic stand for
Multiparent Advanced Generation InterCross
Statistical test for linkage
-LOD score
-LOD = “Logarithm Of the Odds”
LOD = log10(likelihood that two loci are linked/likelihood that two loci are unlinked)
What is pedigree analysis and what is it used for
- A diagram to summarise the inheritance of discrete trait (phenotype) in a family history
- Used to look at simple discrete mendelian traits
Limitations of pedigree analysis
- Ethical, controlling who mates
- Small samples
- Inaccurate and incomplete data due to environmental factors e.g. smoking and diet
What can you determine from pedigree analysis
- Sex linked or autosomal
- Dominant or recessive
- Calculate the probability
Autosomal dominant
- If D denotes a disease allele, then dd denotes genotypes that are disease free
- In most cases DD will be lethal, so all diseased individuals will be heterozygous Dd
What are sex influenced traits
Autosomal traits that act differently in males and females, dominance of a given allele depends on the sex of the bearer. Due to physiological or anatomical reasons.
2 types of molecular markers
- SSR: Simple Sequence Repeats (the number of repeats)
2. SNP: Single Nucleotide Polymorphisms
Linkage mapping with SSRs
- Collect pedigree information
- Use OCR and electrophoresis to determine genotype of family members for several hundred SSR loci distributed throughout the genome
- Use statistical linkage analysis to identify SSRs that are linked (low recombination) to inheritance of the disease allele
- Identify new molecular markers from within the locus, and repeat the linkage analysis with additional families to resolve a narrower map interval
How to work out if 2 loci are unlinked
X=chance of getting parental genotype
Z=chance of getting recombinant genotype
A= No. of non recombinants
B=No. of recombinants
=(X^A)(Z^B)
How to work out if 2 loci are linked
If, θ = recombination frequency from 0 to 0.5
Then,
1 – θ = chance of parental alleles at both loci
θ = chance of recombinant alleles at both loci
Observed “A” non-recombinants and B recombinant
= (1 – θ)^A x (θ)^B
What are SNP
- Molecular marker based on single base-pair substitutions
- Most SNPs occur in non-coding sequence (between genes and within introns)
- SNPs in exons wont alter amino acids
Association mapping
Uses linkage disequilibrium to link phenotypes to genotypes
2 things needed for linkage mapping
- High resolution of genetic variation located on a physical map of a reference genome e.g. human genome
- Large set of phenotypic data
Non-mendelian inheritance
- Jumping genes
- Epigenetics
- Extracellular inheritance
- Maternal effect
- Genomic imprinting
- Microbiotics
Jumping genes
- A transposable element on a DNA sequence that can change its position within the genome
- Occurs during mitosis and can be affected by environment e.g. temperature stress
What is epigentics and 2 examples
The study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself.
- Methylation
- Histone modification
Methylation
A methyl group that tags DNA which either activates or represses a gene
Histone modification
DNA can wind around proteins called histones for compaction and gene regulation
Extranuclear inheritance
- Transmission of genes that occurs outside of the nucleus.
- Occurs in mitochondria and chloroplasts
Origin of mitochondria and chloroplasts
Endosymbiosis
Evidence of symbiosis
-Biochemical evidence of symbiosis:
Mitochondria communicate with the nucleus via trafficking of proteins and RNAs
-Genetic evidence of symbiosis:
The nucleus contains genes that encode mitochondrial proteins
Maternal inheritance
A form of inheritance wherein the traits of the offspring are maternal in origin due to the expression of extranuclear DNA present in the ovum during fertilization.
Petite mutation in budding yeast
They grow small colonies, mutation in mitochondria
2 types of petite mutants
- Segregational mutants
- Mendelian segregation following meiosis
- Genes are located in the nucleus - Vegetative mutants
- non-Mendelian pattern of inheritance
- Genes are located in the mitochondria
4 spores after segregational petites
Tetrad - 4 spores
2 wild types + 2 petites
Different vegetative petites
Neutral or suppressive
Neutral petite tetrad (4 spores)
All wild type, lack most of their mitochondrial DNA, dominated by wild type
Suppressive petite tetrad
4 petites, lack only small segments of mtDNA
Uses of mitochondrial genome sequencing
- Easy to isolate and PCR amplify mtDNA
- Maternal inheritance mtDNA enables analysis of maternal population structure without confusion of male-mediated gene flow
- No recombination of mtDNA so very slow to evolve
Genomic imprinting
- Gene expression in which an allele of the affected gene is marked or ‘imprinted’ in one of the parents, and can be passed on through meiosis to the offspring.
- Done through epigentic mechanism: methylation or histone modification
What is chromosomal mutation
- Changes in chromosome number
- Large scale change in chromosome structure
What is aneuploid
change in number of some but not all chromosomes
Monoploidy
Non-viable in most species as deleterious muataions would be effective
Common cause of new species
- Changes in ploidy
- There is a size increase in ploidy, increase in cell size
2 origins of polyploidy
- Autopolyploid: derived from the same diploid species
2. Allopolyploid: derived from different progenitor species
Origin of hexaploid wheat
Derived from 3 ancestral diploid species
Chemically induced polyploidy
Colchicine: can be used to disrupt spindle assembly and thereby block chromosomal segregation
Meiosis in a triploid
- Produces aneuploid gametes
- Consequence: highly sterile
- Forms a trivalent or bivalent + univalent
- One is pulled by itself either way
Meiosis in tetraploid
Pairing possibilities:
- Two bivalents
- One quadrivalent
- Univalent + trivalent (abnormal)
What causes chromosomes to change in number
- NON-DISJUNCTION, when MEIOSIS malfunctions
- In meiosis 1 there are 4 chromosomes go to one pole
- Results in trisomic or monosomic offspring
- In meiosis 2, two chromosomes go to one pole
Changes in chromosome structure
- Deletions
- Deletion and duplication
- Inversion
- Translocation
They can rejoin or crossover
Miss-aligned repeat sequences
- Some cells have duplicate genes
- Miss pairing of duplicate genes during crossing over results with unequal crossing over
- Gain or loss of repeats
2 types of inversions
- Pericentric inversion: encompasses the centromere
2. Paracentric inversion: does not encompass the centromere
Inversion with crossing over
- Forms loops and the crosses over
- Will create dicentric and acentric chromosomes
Reciprocal translocation
Crossover and pulled apart, can be pulled apart in 3 different planes resulting in different types of translocation
Hetrozygous translocation
One pair interchanged, one normal
Homozygous transloacation
Both pairs interchanged
Population definition
A group of individuals of the same species that are able to interbreed
Purpose of population genetics
- Genetic structure
- Geographical patterns
- Temporal changes
Application of population genetics
- Species conservation and utilization of biodiversity
- Essential for Genome-Wide Association Mapping (GWAM)
what does Hardy weinberg principle show
States that allele and genotype frequencies
Hardy weinberg assumptions
- Infinitely large population
- Random mating amongst individuals
- No new mutations, migration or natural selection
Hardy weinberg equation
Frequency of A allele = p
Frequency of a allele = q
p + q = 1
Total of genotype frequencies: p2 + 2pq + q2 = 1
Causes in change of genetic structure
- Mutation: creates new alleles (lethal, neutral or beneficial)
- Migration (gene flow)
- Natural selection
- Genetic drift
- Non ramdom mating
Different types of selection
- Directional selection
- Stabilising selection
- Disruptive selection
- Balancing selection
What is Directional selection
Favors individuals at one extreme of a phenotypic distribution, which have greater reproductive success in a particular environment
What is stabilising selection
- Favors survival of individuals with intermediate phenotypes
- Extreme phenotypes are selected against
What is distrubtive selection
- Favors the survival of two or more different genotypes that each produce different phenotypes
- Likely to occur in populations that occupy diverse environments
What is balancing selection
- Two or more alleles are kept in balance, and therefore are maintained in a population over many generations
- Heterozygote advantage (HS allele)
What is genetic shift
- Random loss of alleles from a population due to chance event(s)
- Large populations are more stable than small populations
- Result in loss of genetic variation
What is a genetic bottle neck
A sudden decrease in population size caused by adverse environmental factors
What is the founder effect
Dispersal and migration that establish new populations with low genetic diversity
2 types of mating
- Assortative mating
- Individuals with similar phenotypes are more likely to mate
- Increases the frequency of homozygotes - Disassortative mating
- Dissimilar phenotypes mate preferentially
- Favors heterozygosity
