BABS2204 Quiz 2 PDF 2023/2024

Lec 6 - Gene interactions I Learning Outcomes LO1 Understand the importance of linkage for gene mapping LO2 Be able to describe when Mendel's laws break down Mendel's laws First law Diploid individuals carry two copies (alleles) of a gene. The 2 copies segregate in the fo...

Lec 6 - Gene interactions I Learning Outcomes LO1 Understand the importance of linkage for gene mapping LO2 Be able to describe when Mendel's laws break down Mendel's laws First law Diploid individuals carry two copies (alleles) of a gene. The 2 copies segregate in the formation of gametes. Individuals inherit one copy from each parent. In Mendel's experiment, two phenotypes in F2 generation are 3:1 Second law For 2 genes, the pairs of alleles assort independently into gametes (when the genes are on chromosomes) In Mendel's experiment, the phenotypes in F2 generation are 9:3:3:1 When does Mendel's second law (independent assortment) not work? If 2 genes are near each other on the same chromosome, the law of independent assortment breaks Dihybrid do not give 9:3:3:1 ratio of phenotypes A test cross also does not give expected ratio of phenotypes  The fewer recombinant you see in a test cross, the closer the genes are on the chromosome Maximum recombination is 50%. ( In the b-vg example, 17% of offspring were recombinants.) 1.84 < 16.268 at alpha 0.001 We cannot reject the null hypothesis that the chromosomes are unlinked. Despite that both alleles are on the same chromosome Incomplete dominance Two alleles CR and CW each contribute to the phenotype Pink phenotype is intermediate between red and white Note: this is not blending inheritance Codominance  Both phenotypes expressed in heterozygotes E.g MN blood types Multiple alleles Pleiotropy One gene can affect multiply traits E.g a gene might encode a protein that forms a part of more than one protein complex Epistasis: interaction between loci Sometimes, the expression at one locus depends on the genotype of (and expression at) another locus. E.g enzyme pathway with 2 enzymes, C & B Recessive homozygotes at C locus are white Phenotypes of cc and CC depend on whether the genotype at B locus is bb or not Polygenic traits Some traits are influenced by many genes Each gene has a small effect on phenotype  Phenotype - often continuous (e.g height, weight, skin colour, learning ability) Also referred to as quantitative traits - the trait can be measured on a continuous scale rather than binary (yes or no) Complex characters Some traits are “complex” / “multi-factorial” —> due to complicated combination of factors leaders to the phenotype Lec 7 Gene interactions II Learning Outcomes LO1 Understand when Mendel's laws break down LO2 Know the difference between linkage maps and physical maps LO3 Be able to identify modes of inheritance from a pedigree LO2 Know the difference between linkage maps and physical maps Chromosome maps A visual representation of the chromosome's structure, showing the banding pattern when stained (e.g., G-banding). Used in karyotyping to detect large structural abnormalities - Shows the chromosome's overall appearance, but not fine details like gene locations.  Applications: Can determine chromosomal location of contig within a genome assembly Probe is labelled with DNA & fluorescent tag --> this will be hybridised to the chromosome itself (anchoring it) Cons: Imprecise due to low resolution of microscope Related to linkage maps --> physical map (the A, G, T, C after genome assembly) Genetic (Linkage map) Measures genetic distance between genes or markers based on the frequency of recombination during meiosis - Provides an estimate of how often genes are inherited together, not their physical location on the chromosome. Created by recombination mapping (i.e breeding experiments & measuring phenotypes) - they are INDEPENDENT of sequencing More precise than linkage maps, especially useful after DNA sequencing - Provides an exact location of genes or markers on the DNA sequence. Recombination hotspots can occur in different parts of genome --> Will change the linkage distance between 2 loci Different species & sexes can have different levels of recombination (e.g linkage map in males are shorter compared to females due to fewer recombination events in males occurring between 2 loci) Physical map The actual sequencing (A,G, T,C) ~3 billion base pairs Measures the physical distance between genes or markers on chromosome, typically in base pairs (bp). Why is the genomic era important? Not every gene/species is represented in genome browsers Allows us to figure out complex traits (e.g different breeds of sheep that are good for wool/meat) --> important to understand these specific traits/regions of the genome that causes this Recessive epistasis Different relationships Recessive leathal Pedigrees & modes of inheritance LO3 Be able to identify modes of inheritance from a pedigree ** note: this is NOT a good pedigree : Mitochondria is contained within the egg --> No mitochondria is present in sperm head (only in tail) --> Upon fertilisation, the genome from the father is released into the egg & the mitochondria which is contained in tail never enters the egg itself Females pass genes onto every single offspring they have Affected Males DO NOT pass on the genes (mitochondrial genomes do not get passed on) Y Linked Mothers can never pass genes on since they do not have a Y chromosome Fathers never pass onto daughters --> they pass on an X chromosome instead of Y E.g SRY gene --> potential gonad to develop into testes X-Linked dominant Affected males pass the condition to all of their daughters, but none of their sons E.g Hypertrichosis (excess body and facial hair) If affected daughter is heterozygous --> they pass it onto half their offspring (irrespective of sex) Example: X-linked recessive  More males than females have the phenotype Some generations skipped Males are hemizygous (XaY) Fathers have a 50% chance of passing on trait to daughters ONLY mothers pass trait onto sons (never the fathers); obligate carriers Incomplete penetrance The proportion of individuals with the disease-causing allele that develop clinical symptoms --> E.g Polydactyly Not all individuals who have the alleles are responsible for causing the disease/phenotype -->but can still pass it on to offspring Variable expressivity The severity and type of symptoms shown in an individual with the disease-causing allele --> E.g Osteogenesis imperfecta - mutation in gene responsible for collagen Penetrance vs Expressivity Penetrance = proportion of individuals - you either have it or you don't Expressivity = Individual symptoms (can result in variable penetrance) --> the different phenotypes as a result of the single gene mutation Combination of both: suggests that a trait is complex (not a single gene!!) Lec 8 - Epigenetics ​ Learning Outcomes LO1 Be able to describe what chromatin is  LO2 Understand the importance of epigenetics in regulating gene expression LO3 Describe X inactivation and genomic imprinting Epigenetics Epigenetics - phenotypic change in the absence of DNA change. ○ "Over" or "Above" genetics ○ Modifications in gene function that DO NOT involve a change in the DNA base sequence LO1 Be able to describe what chromatin is ○ DNA + Proteins = Chromatin ○ Wound around nucleosomes (subunits of chromatin) ○ Histones (comprises of nucleosomes) Nucleosomes  ○ Made up of an octamer (8 core histones) ○ Histones H1 (holds DNA wrapped around histones in place) ○ Linker DNA in between nucleosomes Higher order structure LO2 Understand the importance of epigenetics in regulating gene expression Transcription ○ RNA pol II (4 on the gene above) ○ Transcription factors required for initiation of gene expression ○ Orange molecule - resultant RNA molecule ○ More Highly expressed a gene is - nucleosomes will dissociate (polymerase can read through faster)  Histone modifications LO2 Understand the importance of epigenetics in regulating gene expression ○ Opening and closing of chromatin via histone residues ○ They are either repressive or associated with turning genes off/ more associated with genes turned on ○ Histone residues/tails --> composed of amino acids that can be modified to change the tail itself ○ Modification can determine whether the tails stick together or repel each other (relax and open the chromatin up to become more accessible the molecular mechanisms required for DNA transcription/translation)  Cellular inheritance of chromatin states LO2 Understand the importance of epigenetics in regulating gene expression ○ Epigenetic modification (histone modification, DNA methylation) relaxes/condenses chromatin to change gene expression ○ Inheritance of these codes it NOT well understood ○ Involves detection & replication of epigenetic marks on new DNA  Histone code: ○ Epigenetic code (almost all) is reset during meiosis (i.e spermatogenesis, oogenesis) ○ DOES NOT reset during genomic imprinting and X inactivation Genomic imprinting LO3 Describe X inactivation and genomic imprinting  Example of a epigenetic code that does not reset during meiosis ○ Genomic imprinting: controlled by imprinting control regions (ICRs) ○ Cis - acting IncRNAs ○ DNA methylation ○ Histone modifications ○ Genomic imprinting is where genes are turned on/off depending on if its inherited from mother or father (Silencing of specific alleles is INDEPENDENT of underlying DNA sequence) --> e.g Paternal: Prader-Wili (7 genes) & Maternal: Angelman syndrome on chromosome 15 Genomic imprinting in mammals ○ Notoriously hard to clone mammals ○ Epigenetic reprogramming in the testis and ovary is skipped  Pathogenesis ○ Reproduction of an embryo from an unfertilised egg (due to imprinting being incorrectly reset) ○ Common in reptiles but NEVER in mammals Kinship theory ○ Explains why genomic imprinting occurs ○ Males have many gametes (significantly more than females) ○ Females have a set number of reproductive events in their lifetime & long gestation periods (partition resources between pregnancies) ○ Males would be turning on genes that promote larger foetal growth compared to females: turning genes off which supress overgrowth ○ Conflicts are what lead us to consider the outcomes when closely related species are crossed over. X-inactivation LO3 Describe X inactivation and genomic imprinting  ○ X inactivation - males have upregulated their single X chromosome (avoids monosomy) to be functionally equivalent to 2X-chromosomes in females ○ This is however, carried on to females which results in a tetrasomy ○ Females have evolved to have X inactivation to silence entire X chromosome ○ Result: single hyperactive X (1 in male), 1 single hyperactive and 1 inactive in females RECAP:  ○ DNA methylation acts to repress gene expression ○ Methylation - a way of changing transcription of DNA segment without changing the sequence (Epigenetics regulation) Example of epigenetic silencing: Tortoiseshell cats ○ Shows that inactive X was not reset during meiosis and remained inactive X through 2 generations ○ Somatically heritable ○ In female mammals, each cell has two X chromosomes, but one of them is randomly inactivated in each cell during early development. This process is called X chromosome inactivation. ○ The gene that controls the tortoiseshell coat color is located on the X chromosome. Different color patches (like black or orange) appear because some cells have one X chromosome active, while others have the second X active, creating a mix of colors.  ○ In Copy Cat's mother, this random inactivation led to the tortoiseshell pattern because some cells expressed the orange gene and others expressed the black gene. ○ However, in Copy Cat, the random inactivation pattern was different, and most of the cells activated the X chromosome carrying the black coat color gene, giving her a black tabby phenotype instead of a tortoiseshell one. Thus, the random nature of X chromosome inactivation explains why the two cats, though genetically identical, have different coat colors. Lec 9 - Complex traits I VP Phenotypic Variance Ve Environmental Variance Vg Genetic Variance Vg = va + Vd Ve = Vp - Vg Complex traits Complex traits - involve multiple genes Each gene (allele) has a small effect on phenotype --> height is influenced by many environmental factors -- known as the Multifactorial hypothesis of multiple traits Mendelian vs Complex Traits Measuring variation --> data is represented as a histogram (shows distribution of measurements) Variance Normal distribution Covariance & Correlation Example data Heritability The proportion of phenotypic variance due to genetics (with caveats) 2 specific definitions:  Broad sense heritability (H^2) - total phenotypic variance due to all genetic factors Additive (h^2) - (sum of the average effects of individual alleles) - ONLY includes effects of genes that are passed from parents to offspring Example: If Vg = 1965 and Ve = 2910, what is the heritability (h2)? VP = Vg + VE = 1965 + 2910 = 4875 h2 = Vg/VP Vg consists of: Va Additive genetic inheritance Vd Variance due to dominance effects Vi Variance due to genetic interactions (epistasis) Ve = Vp - Vg Example: Broad sense heritability Purpose of population variants: Represents the entire population and uses all of the data. i.e if a sub-sample were taken (not all data were used) we would need to correct for biases (e.g n-1)  Heritability is measured for a particular population (with particular genotype frequencies and particular environmental conditions) Note 1: Heritability is therefore not useful for interpreting differences between groups or populations. Note 2: Low heritability does not mean that genes are not involved. Different alleles might just cause a similar phenotype - or there may be no genetic variation at relevant loci (low Vg). High heritability does not mean that the environment doesn't affect phenotypes. Even if height is 100% heritable in a given population, improving health and nutrition could lead to taller individuals. Lec 10 - Complex traits II Estimating broad sense heritability