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Joseph Merritt Ramsey
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This 19 page Class Notes was uploaded by Joseph Merritt Ramsey on Wednesday February 3, 2016. The Class Notes belongs to CELL 2050 at Tulane University taught by Dr. Meenakshi Vijayaraghavan in Winter 2016. Since its upload, it has received 76 views. For similar materials see Genetics in Science at Tulane University.
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Date Created: 02/03/16
January 29, 2016 Chapter 5: Non-Mendelian Inheritance Overview: o What Exactly is Mendelian Inheritance? 1) Defined By Independent Assortment and Law of Segregation 2) The Presence of Gene and the Expression of the Phenotype are Directly Connected o What is Non-Mendelian Genetics? Broad Topics: 1. Nuclear Genes – genes in the nucleus of the cells 2. Epigenetic Inheritance 3. Extranuclear Genes – mitochondria and chloroplasts These are essentially factors that change gene expression without changing the gene sequence The Three Categories of Non-Mendelian Inheritance o 1) Nuclear Genes 1. Maternal Effect Definition – the mother’s genotype determine the offspring’s phenotype o The Father’s and Offspring’s genotypes have nothing to do with the Phenotype o How is this any different than Maternal Inheritance? Inheritance has to do with things being passed on by the mother (some X-Traits, Mitochondrial DNA) Effect merely means some aspect of the mother has an effect on the Genotype Why does this happen? o Some sort of protein accumulation occurs on an Oocyte of Embryo This accumulation occurs because of Diploid surrounding cells o This occurs through the action of Nurse Cells o So, the genes do not affect the Oocyte, but the gene products do Examples: o 1. Shell Style in Water Snail Genotypes (have to do with the cleavage pattern of body development) Dextral (D) is Dominant (to the Right) Sinistral (d) is Recessive (to the Left) Diagram of the Cross How do Nurse Cells Work? (Diagram) This is an example of Oocyte development with the snails o 2. Drosophila Anterior Structures Genotypes – Bicoid genes arrange posterior/anterior axes In this instance, the Nurse Cells affect the embryo’s development (as opposed to egg like above) What types of development genes do Nurse Cells affect? o 1. Early Stages of Cell Cleavage o 2. Body Plan Curvature o 3. Anterior/Posterior and Ventral/Dorsal Axes o 2) Epigenetic Inheritance – refers to patterns of inheritance in which a modification on a nuclear gene of a chromosome occurs that alters gene expression without changing the base pair sequence 1. Dosage Compensation Definition – phenomena that occurs to ensure equal gene expression between male and female with different X chromosome members o Most often refers to X Chromosome Genes, not the semi autosomal genes Animals’ Mechanisms: o I. Marsupial Mammals – paternal X is deactivated in females o II. Placental Mammals – random inactivation of one of the extra X’s occurs o III. Drosophila – X is doubled in the male o IV. Nematodes (Hermaphrodites) – female Sex Chromosome is downregulated o V. Birds – (males are ZZ) Some genes are upregulated in females, some are downregulated in males Examples: Drosophila Apricot Eye Color o We already saw that Eosin eyes are not equal in males and females (cream can occur in males) In this case, Apricot is equal in males and females o So how is the Apricot color equal? 1. Mutated allele has Protein Leakage This allows protein to leak in the Male So to compensate, they produce more 2. Gene modifier effect occurs Sort of the opposite of the cream color effect Enhanced in males Barr Bodies o Overview – What Are They? Scientists began noticing a highly condensed structure in the nuclei of women Only seen in women, so a suspicion of X- Chromosome connection Phenotypically speaking, they also noticed variegated coat patterns in females Also noted that these compactions occurred at varying points, but always at least before the blastula forms But it’s important to note: Barr Bodies have sections that are less compact and are sometimes transcribed, so they’re known as Faculative Heterochromatin Constitutive/Telomeric Heterochromatin are completely inaccessible o The Lyon Hypothesis – How Did We Figure it Out? Lyon observed the expression of an X- Linked Gene, Glucose 6 Phosphate Dehydrogenase (G6PD), which is involved in Sugar Metabolism This particular gene has two types, the fast acting and the slow acting This difference allows them to be sorted in gel electrophoresis Minced cells and spread then thinly to be cultivated as single cell types Found the gel created distinct bands in the individual cultures o Mechanism – How Do They Form? The X-Chromosome has a cell inactivation center (Xic) Having an extra Xic (Extra X Chromosome) causes one to be activated This is done randomly On this activation center are two genes Xist (X Inactive Specific Transcript) – transcribes RNA coating around the Chromosome all the way to the telomere (it’s not considered mRNA because there is no possibility of it being transcribed Tsix – counteracts the Xist o Phenotypes – Why Do Patches Form? This has to do with regional replication, which starts with Blastula formation Each cell randomly turns off one of the X’s After, they continue to replicate, in essence forming large patches of the original cell Diagram 2. Genomic Imprinting January 27, 2016 Chapter 4: Extensions of Mendelian Genetics Continued Limitations of Mendel’s Work Modern Genetics Begins to Ask Why? o So how do other mutations manifest themselves other than the simple above potential mechanisms? 1. Gain of Function 2. Dominant Negative 3. Haploinsufficiency Looking Dominance o 1. Simple Dominance (3:1) o 2. Incomplete Dominance (1:2:1) o 3. Incomplete Penetrance (Varies by Generation) o 4. Overdominance (1:2:1, But Heterozygotes are Selected for) o 5. Heterosis Considering Multiple Alleles Conditional Alleles Codominance Sex Linked Genes Sex Related Traits Lethal Alleles (1:2) o Differentiating Between Codominant, Incomplete Penetrance, and SemitLethal o Variants on Lethal (or more accurately, Genes that appear Lethal) 1. Semilethal Alleles 2. Incomplete Penetrance Effects on Phenotype o 1) Pleiopatry o 2) Gene Interactions o 3) Gene Dosage Effect Important Interactions: o 1. Two Gene Interactions (9:3:3:1) o 2. Epistasis Definition – one gene masks another I. Recessive Complementation Epistasis (9:7) – The recessive alleles together affect another gene (recessive epistasis) Two White Flowers are Bred CCpp (White) X ccPP (White) How? o There’s a molecular pathway needed to have the protein be expressed 1) Precursor (Colorless) 2) Intermediate (Colorless) 3) Functioning Pigment (Anthocyanin) o Each has an intermediate enzyme that functions on the pathway Complementation is often a factor with Recessive Epistasis, too. o In that case, two recessive phenotypes are being considered (hence, complementation) Deafness is another strong example o In this manner, some deaf parents have children who can hear while others don’t – because the parents are homozygous recessive for the same gene, which is one of two complementation and epistatic options o Two options for parents exist (assuming both are deaf) Intergenic Mutation (Occurring on Intragenic Mutation (Occurring on different genes) can result in the same gene) cannot result in complementation. Complementation. AAbb (Deaf) x aaBB (Deaf) AAbb (Deaf) x AAbb (Deaf) = = AaBb (Normal) AAbb (Abnormal) II. Simple Recessive Epistasis (9:3:4) – The Labrador Retriever Two genes are being considered that are part of a different process: o 1. Coat Color o 2. Pigment Depositing onto Shaft Some terms for these genes: o Hypostatic Gene – the gene cannot express itself o Epistatic Gene – the gene affects the expression of another without affecting the code sequence Considerations: o Color Genotypes: BB, Bb – Black bb – brown o Depositing Genotypes (the epistatic gene): E – functioning e – mutated o How is this different than complementation (two recessive lead to dominant)? Complementation is dealing with one process, one function towards phenotypic expression (both flower genes were with color) Simple Recessive Epistasis is two genes and two functions (the lab genes have different functions) o The “default” color for a pigment-less lab is yellow due to pheomelanin presence Punnett Square (9:3:4) III. Dominant Epistasis What’s the difference? o Recessive: homozygous recessive for a gene masks the dominant gene of another o Dominant: heterozygous or homozygous dominant genes mask the gene of another Type 1 (12:3:1): epistatic allele affects both dominant and recessive of another gene o Let’s say AA/Aa = Yellow, aa = Green BB/Bb = No Color, bb = Color o Both colors can be drowned out by the dominant “No Color” Type 2 (13:3): epistatic allele affects only dominant allele of another gene o Let’s say AA/Aa = Yellow, aa = no color pigment BB/Bb = No Color, bb = Color o In this case, it’s only possible for the Dominant allele of the “Color” gene to be drowned out The other does not express itself o 3. Complementation Definition – two recessive alleles give rise to a dominant NEXTCTE phenotype Consider Deafness Example, though o 4. Modifier Genes (8:4:3:1) Definition – genes on separate chromosomes influence each other They are in different loci within the genome (generally separate Chromosomes) Drosophila Eye Color is an Extremely Potent Example What Happened? o It is knows that eye color follows the trends for Drosophila from the X-Chromosome Dominant = Red Recessive = White Eosin = Orange (mutant red) o What they found was a random Cream colored fly in a true breeding Eosin culture What Could Explain It? o There were really only two possibilities: 1. A Completely New Mutations had Occurred 2. A Mutation on another Gene Modified the Eosin Expression o They also knew it wasn’t epistatic, because more flies would have been affected (recall the purple plant had a (9:7 Ratio) What Did They Find? o Decided to run an experiment Bred Wild Type Female with Cream Colored Male Then crossed that generation (because they knew the Cream Had been passed on somewhere) o Found the following gene categories: Eye Color: X w+= Red (Dominant) X w-e= Eosin Color Modifier Gene: C = Normal a c = Modifies Eosin Only o Numbers Results: 8 Red Eyed Females 4 Red Eyed Males 3 Light Eosin (C Slightly Affects) 1 Cream Color (Dysfunctional C) o 5. Gene Redundancy (15:1) Definition – one functional copy is enough to exhibit the gene These studies are run through knockout individuals Normal Traits are discontinuous o So they are an accumulation of proteins and gene expression o So losing one doesn’t often do much But sometimes a trait is affected and determined by two genes o This makes the defective phenotype rare, but more possible o In these instances, we can knock out both genes to see the effects Consider: Seed Shape If Gene “T” and Gene “V” can give normal shape on their own, abnormal shape only comes from both being dysfunctional So “ttvv” is needed for abnormal shape So how does Redundancy develop anyway? The Creation of Paralogs Occurs through the Gene Duplication process o Genes are accidentally inserted into additional spots on Chromosomes o At this point, the Duplicate Genes are still exact copies o Over time, however, mutations accumulate and the genes remain similar, but have small differences, now known as Paralogs Definition: different forms on a gene that reinserted in a new location and retain old function, but not the same gene sequence Gene Duplication does not make Paralogs, but it leads to them o 6. Intergenic Suppressors Definition – the phenotypic effects of one gene are reversed due to a suppressor mutation another gene It’s an Extragenic/Intergenic Suppressor Consider a phenotype that needs two proteins to function conjointly for expression Bristles on insects are an example o Functioning Bristles = Normal Function Protein A (100% Capacity) + Protein B (100% Capacity) o Say One is mutated = Abnormal Function Protein A (50% Capacity) + Protein B (100% Capacity) o Balance Response – Normal Function Protein A (50% Capacity) + Protein B (50% Capacity) Difference between “Extra/Inter” and “Intra” o Suppressor Genes are Intergenic o 7. Duplicate Interactions (9:6:1) In this case, duplicate alleles (affect same trait) can produce a newfound phenotype Let’s take the following example of squash shape: Spherical (Dominant) = AAbb/Aabb/aaBB/aaBb Elongated (recessive) = aabb But Newfound Phenotype Exists When the Dominant Alleles of the two genes mix: o Disk = AaBb/AABb/AaBB The two dominant expression for a new Phenotype January 25, 2016 Chapter 4: Extensions of Mendelian Genetics Continued Limitations of Mendel’s Work Modern Genetics Begins to Ask Why? o So how do other mutations manifest themselves other than the simple above potential mechanisms? 1. Gain of Function 2. Dominant Negative 3. Haploinsufficiency Looking Dominance o 1. Simple Dominance (3:1) o 2. Incomplete Dominance (1:2:1) o 3. Incomplete Penetrance (Varies by Generation) o 4. Overdominance (1:2:1, But Heterozygotes are Selected for) o 5. Heterosis Considering Multiple Alleles Conditional Alleles Codominance Sex Linked Genes Sex Related Traits Lethal Alleles (1:2) o Definition o Genotypic Expressions o Examples Manx Cat Mice Coat o Differentiating Between Codominant, Incomplete Penetrance, and SemitLethal Looking at Heterozygous Individuals Codominant? It’s tempting to say the allele is Codominant because an in between form is expressed But the allele cannot be “partially lethal,” and it occurs before birth So it’s considered a recessive wild-type allele behaving in a recessive manner, even though it’s a dominant allele Incomplete Penetrance? Incomplete penetrance deals with a gene that is actually expressed o Lethal alleles result in the 2:1 ratio because they occur before birth Huntington’s is a good example o Not semilethal, which are often sex specific and affect given ratios o And not lethal either, since they act after birth o Variants on Lethal (or more accurately, Genes that appear Lethal) 1. Semilethal Alleles Kill about half the population in a lethal, before birth manner (hence the applicability of the ‘lethal’ nomenclature) The dominant/recessive “lethal” allele is present in Homozygous manner (Genotypically Speaking), but only half the organisms die Ex) Drosophilia Eyes o The recessive eye color for drosophila is white o But if 100 males are predicted to have the recessive genotype for white eyes, only 50 will even be born Side note: presence only in males suggests hemizygous effects 2. Incomplete Penetrance Different than Lethal or Semi-Lethal, the gene just happens to result in death o So this isn’t even considered lethal because it occurs after birth Ex) Huntington’s Disease o Tripeptide Repeats The Tripeptide ‘CAD’ repeats, but depending on the number functionality can differ Below 26 – Normal 27-30 – Slight Changes (Intermediate) 31-35 – Moderate Changes (Incomplete) 36-39 – Notable Changes (Incomplete) Above 40 – Drastic Changes (Disease) Males vs. Females Female Oogenesis is a much more concentrated, fail prove process that results in minimal coding errors Spermogenesis has more errors, resulting in more repeats of the CAD sequence o Creates various Possible Combinations in Parents Normal + Normal = Small Chance of Disease Incomplete + Incomplete = Decent Chance for Late Onset Incomplete + High = Strong Chance for Early Onset o Looking at those trends, CAD repeats only determines and influence penetrance but not lethality o Anticipation is a notable side effect Each generation shows early and early onset of the disease (trinucleotide repeats) They are incompletely dominant, not purely so Effects on Phenotype o 1) Pleiopatry Definition – one gene influences many phenotypic traits 1) The gene can make a given protein a different stages of cell life 2) The gene protein can affect numerous cell types Example Population: Maori Tribe in New Zealand (Chromosome 7) Respiratory Issues and Sterile What is the common thread? Similar Microtubule Proteins o Sperm Flagella o Respiratory Cilia Additional Example: Mice Coats Tumor Susceptibility, Diabetes Development, and Coat Color are all affected by the same gene o 2) Gene Interactions Definition – two or more different genes influence a given trait Two Types Discrete Multiple Gene (Discrete meaning discontinuous) o There is an Either/Or effect present o No gradient occurs o Ex: Purple and White flowers only Quantitative Multiple Genes (Quantitative Meaning Continuous) o A range occurs, variation Results from polygenic nature (several contributing genes) o Most traits fall into this category o Ex: Height, Skin Color o 3) Gene Dosage Effect Definition – inheritance of single gene depends on particular allele of the gene So having more alleles present could contribute Example: Drosophilia Eye Color Females have a Dark Eoisin (Homozygous Recessive) Males have a light Eosin (Hemizygous) Important Interactions: o 1. Two Gene Interactions (9:3:3:1) How is it Different Than Mendel’s Studies? Presence of Parental Alleles o Mendel’s parent pea generations phenotypes always showed up in the filial generations o They could have various combinations, but nothing in and of itself was novelty Formation of New Dominant Alleles o Here, however, completely new phenotypes are produced Examples Ex) Hen Combs o Roosters have different types of Combs Rose Pea Walnut Single o Have various Genotypes (R) Rose is Dominant to (r) (P) Pea is Dominant to (p) R and P are Codominant to form the Walnut All recessive produces the Single Comb o Punnet Square RRpp (Rose) ) rrPP (Pea Ex) Fur Color o The same thing occurs: AAbb = Tan aaBB = Gray A_B_ = Brown aabb = White o 2. Epistasis (9:7) Definition – one gene masks another The genes affect one another (recessive epistasis) Two White Flowers are Bred CCpp (White) X ccPP (White) It becomes clear that they are somehow epigenetically related (A large number of Purple Show Up – 9:7) How? There’s a molecular pathway needed to have the protein be expressed o 1) Precursor o 2) Intermediate o 3) Functioning Pigment Each has an intermediate enzyme that functions on the pathway o If one enzyme is messed up, the pigment cannot be created o 3. Complementation Definition – two recessive alleles give rise to a dominant phenotype o 4. Modifier Genes Definition – genes on separate chromosomes influence each other o 5. Gene Redundancy Definition – one functional copy is enough to exhibit the gene o 6. Intergenic Suppressors Definition – the phenotypic effects of one gene are reversed due to a suppressor mutation another gene WILL BE COVERED NEXT LECTURE
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