Genetics 1 BLURT! PDF

Genetics 1 BLURT! 1^1^ Importance of Genetics: My Amazing Professor Likes Biology, Ecology, Ethics and History. -- State all the areas/fields where genetics is important. = Medicine, Agriculture, Pharmaceutical industry, Law, Biology, Ecology, Ethics, and History. Model Organisms -- Which Model O...

Genetics 1 BLURT! 1^1^ Importance of Genetics: My Amazing Professor Likes Biology, Ecology, Ethics and History. -- State all the areas/fields where genetics is important. = Medicine, Agriculture, Pharmaceutical industry, Law, Biology, Ecology, Ethics, and History. Model Organisms -- Which Model Organisms are important within genetics? State all organisms used for the study of genetics. = Fly By Your New Plant Zoo Museum. 1. Fly (Drosophila melanogaster) 2. Bacteria (Escherichia Coli -- E coli.) 3. Yeast 4. Nematodes 5. Plants 6. Zebrafish 7. Mouse New technologies used in Genetics -- State the four new technologies used in the field of genetics. = F M K U~f~ 1. Fluorescence in Situ Hybridisation (FISH) -- what is the function of FISH and what is it useful for? = The function of FISH is to visualise and map genetic material in the cell. It is useful for understanding chromosomal abnormalities and genetic mutations. 2. Microarray -- What is the process of a microarray? = DNA molecules attach to a field; DNA molecules are washed to see hybridisation. 3. Knockout Mouse -- What is the process of a knockout mouse? = A gene is removed, and resulting phenotype is observed. 4. Using fluorescence -- What is the advantage of using fluorescence? = visualises where genes are expressed. Latest Technology -- What is the latest technology in genetics & how does it work? = CRISPR Cas9 is a gene editing tool. It stands for clustered regularly interspaced short palindromic repeats. Expanding fields -- State all the expanding fields in genetics. = Great Explorations in Progressive Biology. 1. Genomics 2. Epigenetics 3. Proteomics 4. Bioinformatics DNA -- what is DNA? = DNA is the hereditary material of all life forms except some viruses from RNA. Information Flow of DNA -- Outline the information flow of DNA = DNA → RNA → Protein Genetic variability -- Describe the genetic variability of DNA. = genetic variability is formed by the mutations, the basis of evolution. Meiosis -- What is meiosis? = meiosis is the nuclear division where a diploid cell divides twice to form a haploid cell (daughter cells). Meiosis Key Processes -- What are the key processes of meiosis? = Independent assortment and crossing over. Independent assortment = a process that occurs during meiosis that results in the random separation of homologous chromosomes into daughter cells Dominance and Recessiveness Dominance -- what is meant by the term 'Dominance'? = A dominant trait masks the effect of another allele when together. It is represented by a capital letter. The trait just appears with one dominant allele. Recessiveness -- what is meant by the term 'Recessiveness'? = a recessive allele is the allele that is masked by a dominant allele. It is represented a lowercase letter. The trait appears with two recessive alleles. Homozygotes and Heterozygotes Homozygotes -- What is meant by the term 'homozygote'? = the term homozygous represents two identical alleles for a gene. The traits are consistent for development. Heterozygotes -- What is meant by the term 'heterozygote'? = the term heterozygote represents two unidentical alleles for a gene. The traits are not consistent for development, but the trait can develop in different ways. Key point -- what is the key point of Homozygotes and Heterozygotes? = Organisms are homozygous or heterozygous for a single trait, not overall. Autosomal Dominance -- what is autosomal dominance? Define it. = One faulty gene from one parent causes the trait/disorder. Mnemonic: \"A Dominant gene from one parent **T**akes over.\" Inheritance patterns -- describe the inheritance patterns of autosomal dominance. = 1. Expressed in Both Sexes: Affects males and females equally. Mnemonic: \"Equal Both Sexes\" (EBS)/ 2. Appears in Multiple Generations: Only one faulty gene is needed. Mnemonic: \"Multiple Generations\" (MG). 3. Unaffected Individuals Don't Transmit: If you don\'t have the condition, you can\'t pass it on. Mnemonic: \"No Transmit if Normal\" (NTN). 4. Homozygous Condition: More severe or lethal if both alleles are faulty. Mnemonic: \"Homozygous Severe\" (HS). Examples -- what are some examples of diseases arising from autosomal dominance? = Huntingdon's disease, neurofibromas type 1, familial hypercholesteraemic, etc. Autosomal Recessive -- what is autosomal recessiveness? = It is where two faulty genes from both parents are present to cause a trait/disorder. Bothe sexes are affected equally. Mnemonic for Inheritance Pattern -- describe the inheritance pattern of autosomal recessive. = \"Carrier Parents Random Transmission\" (CPRT) 1. Carrier Parents (CP): Both parents are carriers. 2. Random Transmission (RT): Random chromosome contribution. Mnemonic for Function: - describe the function of autosomal recessive. \"Unaffected Equal Gender Consanguinity Carrier\" (UEGCC) 1. Unaffected Carrier (UC): Two unaffected carrier parents. 2. Equal Gender (EG): Trait is equally expressed in both sexes. 3. Consanguinity Increases (CI): Consanguinity increases the risk. 4. Carrier Children (CC): Typically yields unaffected carrier children. Examples of diseases in autosomal recessive = Mnemonic: \"CF, PKU, SCA\" 1. Cystic Fibrosis (CF) 2. Phenylketonuria (PKU) 3. Sickle Cell Anaemia (SCA) X-Linked Recessive -- What is the definition of X-linked resseiveness? = A genetic condition linked to genes on the X chromosome. Males are more frequently affected because they have only one X chromosome. - Mnemonic: \"X-tra issue in boys\" (X for X-linked, boys more affected). Function -- describe the function and outcomes of X-lined recessiveness. 1. Males affected: Usually more present in males. - Mnemonic: \"Males Almost always\" (MA). 2. Carrier females to sons: Passed from carrier females to their sons. - Mnemonic: \"Carrier Females Pass to Sons\" (CFPS). 3. Affected males' daughters are carriers: Affected males pass the condition to all their daughters, who become carriers. - Mnemonic: \"All Daughters Carry\" (ADC). 4. 50% chance for sons of carrier females: Sons of carrier females have a 50% chance of being affected. - Mnemonic: \"Fifty Percent Sons\" (FPS). 5. Mild symptoms in carrier females: Occasionally, carrier females may show mild symptoms. - Mnemonic: \"Mild Symptoms in Females\" (MSF). Examples - Mnemonic: \"HCD\" - Haemophilia A & B (H) - Colour Blindness (C) - Duchenne Muscular Dystrophy (D) X-Linked Dominance -- what is the meaning of the term 'X-linked dominant'? = A genetic condition where a single copy of the faulty gene on the X chromosome can cause the disorder in both males and females. Males often have more severe symptoms. - Mnemonic: \"X equals dominant traits\" (XDT) Function -- describe the function and outcomes of X-linked dominance 1. No male-to-male transmission: Affected males do not pass the disorder to their sons. - Mnemonic: \"No Male-to-Male\" (NMM) 2. Affected males produce unaffected sons and affected daughters: All sons are unaffected; all daughters are affected. - Mnemonic: \"Unaffected Sons, Affected Daughters\" (USAD) 3. Affected females produce both affected and unaffected offspring: Affected females can have both affected and unaffected children. - Mnemonic: \"Both Affected Unaffected\" (BAU) 4. Males are often more severely affected, can be lethal: Males show more severe symptoms. - Mnemonic: \"Severe Male Lethal\" (SML) Examples -- State examples of diseases that arise from X-linked dominance. - Vitamin D Resistant Rickets, Rett Syndrome, Goltz Syndrome. - Mnemonic: \"VRGS\" - Vitamin D Resistant Rickets - Rett Syndrome - Goltz Syndrome Y-linked inheritance -- What is Y-linked inheritance? Define it. = A genetic condition where the mutated gene is on the Y chromosome, affecting only males. - Mnemonic: \"Y genes are male only\" (YMO). Function -- What is the function of Y-linked inheritance and what are the outcomes? 1. Affected males transmit to all sons: All sons inherit the condition from affected fathers. - Mnemonic: \"All Sons Transmitted\" (AST). 2. No transmission to daughters: Daughters cannot inherit the condition because they get the X chromosome from their fathers. - Mnemonic: \"No Daughter Inheritance\" (NDI). 3. Exclusively male-to-male: Only males have Y chromosomes, so it's only passed from father to son. - Mnemonic: \"Male to Male Only\" (MtMO). Mendel's 4 Postulates -- What are Mendel's 4 Postulates? = 1.Unit Pairs, Dominance/Recessiveness, Segregation, Independent Assortment. 1\. Unit Factors in Pairs - Definition: Genetic characters are controlled by unit factors (genes) existing in pairs in individual organisms. - Mnemonic: \"Unit Pairs\" (UP) - Unit: Genes are unit factors. - Pairs: Exist in pairs. 2\. Dominance/Recessiveness - Definition: In a pair of unit factors for a single trait, one unit factor is dominant and the other is recessive. - Mnemonic: \"Dominant Over Recessive\" (DOR) - Dominant: One unit factor is dominant. - Recessive: The other is recessive. 3\. Segregation - Definition: Paired unit factors separate during gamete formation. - Mnemonic: \"Separate in Gametes\" (SG) - Separate: Unit factors separate. - Gametes: During gamete formation. 4\. Independent Assortment - Definition: Traits assort independently during gamete formation. All possible combinations of gametes form with equal frequency. - Mnemonic: \"Independent Assortment\" (IA) - Independent: Traits assort independently. - Assortment: Formation of gametes. Combining Mnemonics: - \"Units Paired, Dominant Over Recessive, Separate in Gametes, Independent Assortment\" (UP DOR SG IA). Addition Rule -- Define the addition rule = Probability of any one of two or more exclusive events occurring is calculated by adding their individual probabilities. - Mnemonic: \"Add for Exclusive Events\" (AEE) - Example: Probability of a child being a girl or a boy is 1 (½ + ½ = 1). Multiplication Rule -- define the multiplication rule = Probability of two or more independent events occurring together is the product of their individual probabilities. - Mnemonic: \"Multiply for Independent Events\" (MIE) - Example: Probability of having 5 girls in a row is 1/32 (½ x ½ x ½ x ½ x ½ = 1/32). Trihybrid Cross Example - Definition: Use separate Punnett squares for each trait to determine the probability of offspring being AaBbCC from a cross between AaBbCc and AaBBCC. - Mnemonic: \"Three Traits Probability\" (TTP) Mendel\'s Experiment 1. Crossing Pea Plants - Mnemonic: \"Crossed Pea Plants\" (CPP) - Detail: Crossed white and purple flowered pea plants. - Outcome: All F1 hybrids were purple. 2. F2 Generation - Mnemonic: \"F2 Ratio\" (F2R) - Detail: F2 generation had a 3:1 ratio (purple to white). Principles 1. Alleles - Mnemonic: \"Allele Position\" (AP) - Detail: Alternative forms of a gene occupying specific positions on chromosomes. 2. Inheritance - Mnemonic: \"Inherited Factors\" (IF) - Detail: Parents pass \"heritable factors\" (genes). 3. Random Selection - Mnemonic: \"Random Gene\" (RG) - Detail: Each parent has two copies of a gene; either one can be passed to the child. 4. Segregation - Mnemonic: \"Separation of Alleles\" (SA) - Detail: Alleles separate to form gametes. Explanation - Allele Separation - Mnemonic: \"Alleles Separate\" (AS) - Detail: During the formation of reproductive cells, alleles are separated, so offspring inherit one allele from each parent. Combined Mnemonics - Experiment: CPP F2R - Principles: AP IF RG SA - Explanation: AS Genetics 2 BLURT! 2^1^ 1. Complete Dominance -- What is the definition of complete dominance? = Phenotypes of the heterozygote and dominant homozygote are identical. - Explanation -- Provide extra detail on complete dominance. = In complete dominance, if you inherit one copy of a dominant gene (heterozygote) or two copies (homozygote), you will look the same. - Mnemonic: \"Complete Same\" (CS) 2. Incomplete Dominance -- What is the definition of incomplete dominance? = incomplete dominance is the Phenotype of F1 hybrids is intermediate between the phenotypes of the two parental varieties. - Explanation - Provide extra detail on incomplete dominance? = Incomplete dominance is like mixing paint. If you have a red flower gene and a white flower gene, the offspring (F1 hybrid) will be pink, halfway between red and white. Neither gene is completely dominant, so you get something in between. - Mnemonic: \"Incomplete Mix\" (IM) 3. Codominance - Both alleles are expressed equally and distinctly. - Explanation: Codominance is like wearing a striped shirt. If you have one gene for red and one for white, instead of mixing (like in incomplete dominance), both colours show up separately. - Mnemonic: \"Codominance Stripes\" (CS) Codominance Details -- Provide 4 characteristics of codominance. 1. Two Alleles at a Locus Produce Different and Detectable Gene Products - Mnemonic: \"Two Detectable Products\" (TDP) - Example: One allele produces red pigment, the other produces white pigment -- both colours show up separately. 2. No Dominance or Recessiveness - Mnemonic: \"Neither Masks\" (NM) - Explanation: Neither allele masks or hides the other; both alleles are expressed equally. 3. No Intermediate Phenotype (Not Incomplete Dominance) - Mnemonic: \"No Blend\" (NB) - Explanation: Traits don't blend; both traits appear separately and fully. 4. Example: ABO Blood Group in Humans - Mnemonic: \"ABO Blood Group\" (ABG) - Explanation: AB Blood Type: One allele for A, one for B -- both A and B antigens are expressed equally. Combined Mnemonics for Codominance - TDP NM NB ABG Summary Mnemonics for Variations on Dominance - Complete Dominance: CS (Complete Same) - Incomplete Dominance: IM (Incomplete Mix) - Codominance: CS (Codominance Stripes) and detailed: TDP NM NB ABG Conventions -- What are the 4 types of conventions? 1. Wild-Type (wt) Allele -- what is a wild-type allele? = The version of a gene most frequently found in nature, often dominant. - Mnemonic: \"Wild-Type = Natural Dominant\" (WTND) 2. Dominant Alleles -- what is a dominant allele? = Indicated by an italic uppercase letter (e.g., D). Encode proteins that function normally and are produced in the right amounts. - Mnemonic: \"Dominant Uppercase = Normal Protein\" (DUNP) 3. Recessive Alleles -- what is a recessive allele? = Indicated by an italic lowercase letter (e.g., d). Less common in natural populations. Cause a reduction in the amount or function of the encoded protein. Inherited in a recessive fashion, meaning two copies are needed to see the effect. - Mnemonic: \"Recessive Lowercase = Reduced Protein\" (RLRP) 4. No Dominance - Definition: Italic uppercase letters and superscripts denote alternative alleles (e.g., R1, R2, CW, CR). - Mnemonic: \"No Dominance = Alternative Alleles\" (NDAA) Making Pigment -- Describe how Pigment is made **1.** MC1R Gene -- Describe the function of the MSR gene. - Expressed in pigment-producing cells: In the membrane. - Regulates light or dark pigment: Decides pigment type. - Mnemonic: \"MC1R = Membrane Controls 1 pigment, Regulates colour\" (MC1R) 2\. Activation by MSH -- Describe the activation by MSH. - MSH binds to MC1R: Increases cAMP levels. - High cAMP → Dark pigment (melanin): Leads to melanin production. - Mnemonic: \"MSH = Makes Skin Hue dark\" (MSH) 3\. Deactivation by ASP -- Describe the deactivation by AS - ASP binds to MC1R: Decreases cAMP levels. - Low cAMP → Orange pigment: Leads to orange pigment production. - Mnemonic: \"ASP = Alters Skin Pigment light\" (ASP) Pigment Production Process: - Pigments like melanin are produced by cells, affecting hair, skin, and eye colour. - MC1R gene is crucial in regulating this process. Details: - MC1R Gene: Codes for a protein in the membrane of pigment-producing cells (melanocytes). Controls pigment production. - MSH (Melanocyte-Stimulating Hormone): Binds to MC1R, increasing cAMP levels, leading to dark pigment production (e.g., melanin). - ASP (Agouti Signalling Protein): Binds to MC1R, decreasing cAMP levels, and leading to orange pigment production. Simplified Mnemonics: - MC1R: Melanin Control 1 Regulator - MSH: Makes Skin Hue dark - ASP: Alters Skin Pigment light Genetic Basis of Lethal Alleles: The Bombay Phenotype -- state the characteristics of the Bombay phenotype. 1. Woman Type O with Parent Type AB - Explanation: Appears to have blood type O based on a blood test, but genetically has alleles for B. Unusual because her parent has AB blood type. - Mnemonic: \"Woman O blood with AB Parent\" (WOAP) 2. Homozygous Recessive for FUT1 Allele - Explanation: Two copies of mutated FUT1 gene prevent making functional protein for adding fucose to H substance. Causes Bombay Phenotype. - Mnemonic: \"FUT1 = Fucose Unable To add 1\" (FUT1) 3. No Fucose on H Substance - Explanation: Lack of fucose means no substrate for A or B antigens. Blood appears type O despite having A or B alleles. - Mnemonic: \"No Fucose = O type Appearance\" (NFOA) Bombay Phenotype Definition -- Define what the Bombay Phenotype is. - Explanation: A rare genetic condition where a person has blood type O despite having alleles for A or B blood types due to a mutation preventing the formation of A or B antigens. - Mnemonic: \"Bombay Phenotype = O Appearance, No Antigens\" (BP OANA) Multiple Alleles -- define what multiple alleles are. = When more than two forms of a gene exist within a population. Key Points -- what are the key points of multiple alleles? = 1. Existence in Population - Explanation: More than two possible alleles for a single gene can exist in a population. - Mnemonic: \"More Alleles In Population\" (MAIP) 2. Individuals Inherit Up to Two Alleles - Explanation: Each person inherits two copies of each gene, one from each parent. - Mnemonic: \"Two Alleles from Parents\" (TAFP) 3. Three or More Alleles in Population - Explanation: Refers to the presence of multiple alleles in a population, as seen in rabbit coat colour. - Details -- State the 3 characteristics of multiple alleles. - Modification in Multiple Ways: Genes can mutate in different spots, creating different alleles. - Different Alleles, Not Always Different Phenotypes: Each mutation results in a new allele, but not necessarily a visible change. - Population-Level Study: Multiple alleles are studied at the population level. - Mnemonic: \"Rabbit Coat Multiple Alleles\" (RCMA) Example Dominance Hierarchy in Rabbit Coat Colour: - C+ \> Cch \> Ch \> C - Mnemonic: \"C+ Chinchilla, Chimera, Clear\" (C+ Cch Ch C) - Example: ABO blood type system (A, B, O). Lethal Alleles -- what are lethal alleles? = Alleles that can cause the death of an organism, usually when homozygous. Key Points -- what are the key points of lethal alleles? = 1. Homozygous State -- what does the term 'homozygous state' mean? = Two copies of a lethal allele result in non-survival. - Mnemonic: \"Homozygous Non-Survival\" (HNS) 2. Recessive Lethal Ratios -- what does the term 'recessive lethal ratio' mean? = Typically gives a 2:1 ratio in genetic crosses due to non-survival of homozygous recessive individuals. - Mnemonic: \"Recessive Lethal Ratios = 2:1\" (RLR 2:1) 3. Deletion Affecting Another Gene -- what does it mean to delete after another gene? = AY allele deletion affects the Merc gene, which is critical for normal embryonic development. Loss of Merc gene function leads to embryonic death if two AY alleles are inherited. - Mnemonic: \"AY Affects Merc\" (AYAM) Visual Example The image shows a Punnett square illustrating the inheritance pattern of lethal alleles with the following genotypes: - AY/AY: Non-survival (X) - AY/A: Viable - A/A: Viable This visual demonstrates the concept of recessive lethal alleles and their impact on genetic ratios, resulting in a typical 2:1 ratio of heterozygous to homozygous normal offspring. Epistasis Definition -- Define what epistasis is. = The expression of one gene pair masks or modifies the expression of another gene pair. - Mnemonic: \"Epistasis Suppresses Traits\" (EST) Example of Epistasis -- Provide an example of epistasis. = Homozygous presence of a recessive allele may prevent or override the expression of other alleles at a second locus. - Mnemonic: \"Recessive Overrides Allele\" (ROA) - Epistatic -- what does the term 'epistatic' mean? = Alleles at the first locus. - Hypostatic -- what does the term 'hypostatic' mean? = Alleles at the second locus. - Mnemonic: \"Epistatic First, Hypostatic Second\" (EFHS) Epistasis and the Bombay Phenotype -- what are the end results of the Bombay phenotype in a cross and what are the gametes? = - Cross: IAIBHh x IAIBHh - Gametes: IAH, IAh, IBH, Ibh (from each parent) Pigmentation in Dogs and Epistasis -- State and describe the 5 Key points in the process of pigmentation and epistasis in dogs. 1. Two Genes Involved -- what are the 2 genes involved? - E (MC1R Receptor): Controls pigment production. - B (Enzyme): Helps make pigment. - Mnemonic: \"Enzyme and MC1R Both Make Pigment\" (EMBP) 2. Epistatic Interaction -- what is the epistatic interaction? - Interaction between E and B determines coat colour: One gene can mask or modify the effect of another. - Mnemonic: \"Epistatic Modifies Pigment\" (EMP) 3. Modified Ratios -- what is the typical mendelian dihybrid ratio and what is it modified to? = Changes 9:3:3:1 ratio to 9:3:4 due to epistasis. - Mnemonic: \"Modified Ratio Epistasis\" (MRE) 4. Genes E and B -- what is the function of the E and B gene? = - E (MC1R): Controls whether pigment is made. - B (Enzyme): Determines the type of pigment (black or brown). - Mnemonic: \"Enzyme MC1R Pigment\" (EMP) 5. Requirement for Black Pigment -- what is the requirement for black pigment? = - One dominant copy of both genes needed for black pigment. - If E gene is recessive (ee), no black or brown pigment is made, resulting in a lighter color (yellow). - Mnemonic: \"Black Needs Enzyme MC1R\" (BNEM) Visual Example: Pigmentation in Dogs - Genetic Interactions: - what are the three genetic interactions of dogs pigmentation? = Black Pigment (B-E-), Brown Pigment (bbE-), Yellow Pigment (\--ee) - Black Pigment (B-E-) -- what happens to the black pigment? = Normal receptor and enzyme produce black pigment. - Brown Pigment (bbE-) -- what happens to the brown pigment? = Normal receptor but loss of function enzyme produces brown pigment. - Yellow Pigment (\--ee) -- what happens to the yellow pigment? = Loss of function mutation in the receptor results in yellow pigment, regardless of enzyme. Epistasis and the Fox Squirrel -- As epistasis occurs in the fox squirrel what is the mutation that occurs and what is the outcome; what happens when a constant dark pigmentation occurs? = 1\. ASP Gene Mutation -- what happens the ASP gene is mutated? = In the fox squirrel, the ASP gene is mutated, causing a loss of function. - Mnemonic: \"ASP gene Stopped Producing\" (ASP) 2\. Constant Dark Pigment Production -- what happens when there is constant dark pigmentation? = The mutation means MC1R is no longer deactivated by ASP. As a result, MC1R remains activated by MSH, leading to continuous dark pigment production. - Mnemonic: \"Continuous Dark Pigment\" (CDP) Explanation -- why does the ASP gene mutation and constant dark pigmentation occur in fox squirrels occur, provide the 2 impacts? = High cAMP Levels, Mutation Impact. - High cAMP Levels -- what is the effect of high cAMP levels? = MC1R receptor activated by MSH results in dark pigment production. - Mutation Impact -- what is the effect of mutation on ASP? = ASP mutation fails to deactivate MC1R, so the receptor stays on, producing only black pigment. - Mnemonic: \"High cAMP, Mutation Impact\" (HCMI) Penetrance, Expressivity, Epistasis, Pleiotropy -- what do these 4 terms refer to? = These terms refer to how genes can alter phenotypic expression. Penetrance -- what does the term 'penetrance' mean? = The percentage of individuals with a specific genotype who express the expected phenotype. - Example -- provide an example for penetrance. = Polydactyly (extra fingers/toes). - Mnemonic: \"Percentage Expressing Trait\" (PET) Incomplete Penetrance -- what does the term 'incomplete penetrance' mean? = Not all individuals with the genotype express the trait. - Example -- using the polydactyl example state the outcome using numbers for the example of incomplete penetrance. = Polydactyly - 42 people have the allele, but only 38 show the trait (90% penetrance). - Calculation Example: Probability of long fingers (recessive trait) with 80% penetrance. Heterozygous parents\' first child: ¼ x 80% = 20%. - Mnemonic: \"Incomplete Expression Percentage\" (IEP) Expressivity Definition -- Define expressivity. = The degree to which a character is expressed. - Example -- provide an example for expressivity. = Lobe Eye Mutation - Trait varies in how it manifests among individuals. - Mnemonic: \"Degree of Trait Expression\" (DTE) Pleiotropy Definition -- what does pleiotropy mean? = Expression of a single gene with multiple phenotypic effects. - Mnemonic: \"Pleiotropy Multiple Effects\" (PME) Examples -- State 2 examples of pleiotropy. = Marfan syndrome and mutation in mice. 1. Marfan Syndrome -- what is the Marfan syndrome? = Autosomal dominant gene for fibrillin affects eyes, aorta, and bones. - Mnemonic: \"Marfan Syndrome Effects\" (MSE) 2. Mutation in Mice -- what mutation occurs in mice and what is the outcome? = ASP gene mutation affects metabolism, leading to obesity. - Mnemonic: \*\*\"ASP\" = Affects Systemic Processes\" (ASP) Pleiotropy and the MC1R -- how does pleiotropy and the MC1R mutation give red hair? = Red Hair and MC1R Mutation: Low cAMP levels cause orange pigment; redheads need more painkillers, are more susceptible to melanomas. - Mnemonic: \"MC1R Red Hair Phenotypes\" (MRHP) Sex-Limited Inheritance -- what is sex-limited inheritance? = Phenotype expression limited to one sex. - Mnemonic: \"Sex-Limited = One Sex\" (SLOS) Example -- provide an example of sex-limited inheritance. = Feather Plumage in Chickens. - Genetics: Autosomal gene controls plumage. - Mnemonics: - \"Hen Dominant\" (HD) - \"Cock Recessive\" (CR) Genotypes -- what are the genotypes of feathered chickens? = - Genotype hh: Females - hen-feathered, Males - cock-feathered. - Genotype Hh, HH: Both sexes - hen-feathered. Sex-Influenced Inheritance -- what does sex- influenced inheritance mean? = Phenotype influenced by sex, not limited to one sex. - Mnemonic: \"Sex-Influenced = Both Sexes\" (SIBS) Example -- what is an example of sex-influenced inheritance? = Pattern Baldness in Humans - Genetics: Autosomal gene with B allele (dominant in males, recessive in females). - Mnemonic: \"Bald Pattern Genetics\" (BPG) Genotypes -- what are the genotypes of pattern baldness genetics? = - Genotype BB: Both sexes - bald. - Genotype Bb: Females - not bald, Males - bald. - Genotype bb: Both sexes - not bald. - Influence -- what is the influence of the genotypes within pattern baldness? = Related to male sex hormones; can be reversed in females by treating underlying conditions. Environmental Effects Temperature - Evening Primrose: Red flowers at 23°C, white at 18°C. - Siamese Cats and Himalayan Rabbits: Darker fur in cooler areas due to temperature-sensitive enzyme. - Mnemonic: \"Environmental Temperature Effects\" (ETE) Genetics 3 BLURT! 3^1^ Small-Scale Mutations -- what is a small-scale mutation? = These affect one or a few nucleotides of a gene. 1. Base Substitutions -- define the meaning of a base substitution. = A nucleotide is replaced with another. - Example -- provide an example of base substitution = Changing an \"A\" (adenine) to a \"G\" (guanine). - Effect: Might not affect the final protein or could drastically change it. - Mnemonic: \"Base Swap\" (BS) 2. Frameshift Mutations (Deletions or Insertions) -- what is a frameshift mutation? = Removal or addition of a nucleotide alters every codon after the mutation. - Example: Sentence Analogy: "THE CAT RAN" → deleting \"T\" results in "HEC ATR AN\..." - Effect: Scrambles the gene, changing the protein significantly. - Mnemonic: \"Frame Shift Disaster\" (FSD) Large-Scale Mutations -- what is a large-scale mutation, and where do they occur? = These occur at the chromosome level, affecting large sections of DNA. 1. Deletions -- what is a deletion? = A section of the chromosome is missing (like a missing paragraph). - Mnemonic: \"Deletion Drop\" (DD) 2. Duplications -- what is a duplication? = A section is repeated, adding extra information (like copying and pasting a paragraph twice). - Mnemonic: \"Duplication Double\" (DD) 3. Inversions -- what is an inversion mutation? = A section of DNA is flipped, changing the order of the instructions (like reading a paragraph backwards). - Mnemonic: \"Inversion Inverse\" (II) 4. Insertions -- what is an insertion mutation? = A large piece of one chromosome is inserted into another chromosome (like cutting a page from one book and pasting it into another). - Mnemonic: \"Insertion Insert\" (II) 5. Translocations -- what is a translocation mutation? = Sections of two different chromosomes are swapped (like exchanging pages between two books). - Mnemonic: \"Translocation Trade\" (TT) Effects of Mutations on Polypeptides 1. Base Substitution -- State the 3 types of base substitutions and their function. - Silent: Causes no change in the protein. - Missense: Changes one amino acid. - Nonsense: Changes to a stop codon. - Mnemonic: \"Silent Missense Nonsense\" (SMN) 2. Addition or Deletion of One Single Base - Frameshift: Produces a different amino acid sequence. - Mnemonic: \"Add or Delete Frameshift\" (ADF) Faulty DNA Repair: Nucleotide Excision Repair (NER) - NER -- what is NER? = A repair system that removes and correctly replaces damaged sections of DNA, particularly those caused by UV light. - Mnemonic: \"Nucleotide Excision Repair\" (NER) 1\. Mutations in Repair Enzymes - Example: Xeroderma pigmentosum (XP) - autosomal recessive disorder. - Effects: Abnormal skin pigmentation and a deficiency in the ability to repair UV-induced DNA damage. - Cause: Mutations in NER genes reduce or eliminate repair capability. - Mnemonic: \*\*\"XP\" = Xeroderma Problems\" (XP) Xeroderma Pigmentosum (XP) - Cause: Mutations in genes responsible for NER. - Symptoms: Abnormal skin pigmentation under sunlight. - Deficiency: Inability to repair UV damage. - Consequence: Increased risk of skin cancers. - Mnemonic: \*\*\"XP\" = Xposure Problems\" (XP) NER Mechanism (Detailed Steps) 1. UvrAB Scans for DNA Damage - Function: UvrAB proteins act as \"inspectors\" finding damaged spots. - Mnemonic: \"Scanning UvrAB\" (SU) 2. UvrAs Released; UvrC Binds - Process: UvrA leaves, UvrC starts repair. - Mnemonic: \"UvrC Binds\" (UB) 3. Cuts Made 5\' and 3\' to Damage - Action: UvrC makes incisions on both sides of the damage. - Mnemonic: \"Cutting UvrC\" (CU) 4. UvrD Binds and Unwinds Region - Role: UvrD unwinds and removes the damaged DNA. - Mnemonic: \"Uwrapping UvrD\" (UU) 5. DNA Polymerase I Fills in the Gap - Function: DNA Polymerase I fills the gap with new nucleotides. - Mnemonic: \"Polymerase Fills\" (PF) 6. DNA Ligase Joins the DNA Segments; Repair is Complete - Final Step: DNA ligase seals the repaired section. - Mnemonic: \"Ligase Seals\" (LS) Faulty DNA Repair: Nucleotide Excision Repair (NER) NER Overview: A DNA repair mechanism that fixes helix-distorting lesions caused by UV light, chemical carcinogens, and certain chemotherapy drugs. Types of NER Pathways 1. Global Genome NER (GG-NER) - Function: Repairs damage anywhere in the genome. - Damage Recognition: Primarily by XPC protein, supported by DDB2 for UV-induced damage like cyclobutane pyrimidine dimers (CPDs). - Mnemonic: \"Global Genome NER\" (GG-NER) 2. Transcription-Coupled NER (TC-NER) - Function: Repairs damage on the active (transcribed) strand of DNA during transcription. - Damage Recognition: RNA polymerase stalls at the DNA lesion, and CSB protein helps recruit the repair machinery. - Mnemonic: \"Transcription-Coupled NER\" (TC-NER) Key Steps in NER 1. Damage Recognition - GG-NER: XPC and HR23B recognize helix distortions. - TC-NER: RNA polymerase stalling recruits CSB. - Mnemonic: \"Damage Recognition\" (DR) 2. DNA Unwinding - Complex: TFIIH (with XPB and XPD helicases) unwinds the DNA around the damage. - Mnemonic: \"DNA Unwinding\" (DU) 3. Excision of Damaged Strand - Proteins: XPF-ERCC1 and XPG make cuts on both sides of the damage, removing a segment of around 24-32 nucleotides. - Mnemonic: \"Excision Cuts\" (EC) 4. Repair Synthesis - Role: DNA polymerases fill in the gap using the undamaged strand as a template, ensuring high-fidelity repair. - Mnemonic: \"Repair Synthesis\" (RS) 5. Ligation - Function: DNA ligases (I or III) seal the repaired section to complete the process. - Mnemonic: \"Ligation Seal\" (LS) Important Proteins in NER - XPC: Recognizes damage in GG-NER. - DDB2: Helps XPC recognize UV-induced lesions like CPDs. - CSB: Recognizes damage in TC-NER (via RNA polymerase stalling). - TFIIH: Helicase that unwinds DNA at the damage site. - XPF-ERCC1 & XPG: Endonucleases that cut the damaged strand. - DNA Polymerases: Fill in the gap. - DNA Ligases: Seal the repaired DNA. Why NER is Important - Prevents Mutations and Diseases: NER helps prevent mutations and diseases like xeroderma pigmentosum (XP) by fixing damage caused by UV light and chemicals. - Risk of Cancer: Mutations in NER-related genes (like XPA, XPC) can impair the body\'s ability to repair DNA damage, leading to increased cancer risk. Gain of Function Mutation - Definition: A mutation that confers new or enhanced activity on a protein. - Example: A protein that normally regulates cell growth may, after a gain-of-function mutation, promote faster or uncontrolled growth, potentially leading to cancer. - Mnemonic: \"Gain Function = Enhanced Activity\" (GFEA) Loss of Function Mutation - Definition: A mutation that results in reduced or abolished protein function. - Example: A gene responsible for an enzyme may, when mutated, produce a nonfunctional enzyme, causing harmful molecule accumulation. - Mnemonic: \"Loss Function = Reduced Protein\" (LFRP) Dominant Negative Mutation - Definition: A mutation whose gene product adversely affects the normal, wild-type gene product. - Example: A mutant protein that is part of a team (like pieces in a machine) can disrupt the whole process if it doesn't work properly, even if the normal version is present. - Mnemonic: \"Dominant Negative = Disrupts Normal\" (DNDN) Dominant and Recessive Mutations - Dominant Mutations: Require only one copy of the mutated gene to affect the phenotype. - Recessive Mutations: Require two copies of the mutated gene to affect the phenotype. - Mnemonic: \"Dominant = One, Recessive = Two\" (DORT) Osteogenesis Imperfecta (OI) - Dominant Negative Mutation 1. Mutant Allele Interferes with Normal Allele - Explanation: Mutant gene disrupts the function of the normal gene, making the collagen ineffective. - Mnemonic: \"Mutant Interferes\" (MI) 2. COL1A1 and COL1A2 Genes - Explanation: Encode the α1 and α2 chains that form type 1 collagen, providing strength to bones and tissues. Mutant collagen chains combine with normal ones, forming defective collagen fibers. - Mnemonic: \"Collagen Genes\" (CG) 3. Variable Expression of Disease - Explanation: Severity varies among individuals, from mild symptoms to severe bone deformities. - Mnemonic: \"Variable Expression\" (VE) 4. Bone Fragility - Explanation: Defective collagen leads to weak bones prone to fractures. - Mnemonic: \"Bone Fragility\" (BF) 5. Bone Deformity - Explanation: Repeated fractures and improper healing cause bone deformities. - Mnemonic: \"Bone Deformity\" (BD) 6. Hearing Loss - Explanation: Fragile or deformed ear bones cause hearing loss. - Mnemonic: \"Hearing Loss\" (HL) 7. Blue Sclera - Explanation: Thin, fragile collagen in the sclera allows underlying veins to show through, giving a blue tint. - Mnemonic: \"Blue Sclera\" (BS) Achondroplasia - Gain of Function Mutation 1. Mutation in Fibroblast Growth Factor Receptor Type 3 (FGFR3) - Explanation: Mutation in the FGFR3 gene, which regulates bone growth by inhibiting excessive cartilage growth. - Mnemonic: \"FGFR3 = Factors Governing Bone Growth\" (FGBG) 2. Receptor Promotes Differentiation of Cartilage to Bone - Explanation: FGFR3 acts as a brake on cartilage growth, converting cartilage to bone for limb and spine development. - Mnemonic: \"FGFR3 Cartilage To Bone\" (CTB) 3. Mutant is Constitutively Active - Explanation: Mutation causes FGFR3 to be always \"on,\" limiting cartilage growth and converting it to bone prematurely. Results in shortened limbs, while the trunk grows normally. - Mnemonic: \"FGFR3 Always On\" (AO) 4. 75% from New Mutations - Explanation: About 75% of Achondroplasia cases arise from spontaneous new mutations, often in the sperm of the father, increasing with advanced paternal age. - Mnemonic: \"New Mutations = 75%\" (NM 75%) Familial Hypercholesterolemia -- Haploinsufficiency 1. Autosomal Dominant - Explanation: One mutated gene from either parent causes the disorder. - Mnemonic: \"Autosomal Dominant\" (AD) 2. Mutations in the LDLR Gene - Explanation: LDL receptors remove LDL cholesterol from the blood. Mutations lead to faulty or missing receptors. - Mnemonic: \"LDLR = Cholesterol Removers\" (CR) 3. Heterozygotes Have Half the Number of LDL Receptors - Explanation: Individuals with one normal LDLR gene and one mutated gene have half the normal number of LDL receptors. - Mnemonic: \"Half LDLR\" (HL) 4. Plasma Cholesterol Levels High - Explanation: Less LDL cholesterol cleared from the blood, leading to high cholesterol levels. - Mnemonic: \"High Cholesterol\" (HC) 5. Cellular Cholesterol Uptake Reduced - Explanation: Fewer LDL receptors result in reduced cholesterol uptake by cells. - Mnemonic: \"Reduced Uptake\" (RU) Cystic Fibrosis (CF) - Autosomal Recessive 1. Autosomal Recessive - Explanation: Two mutated copies of the gene are needed to show symptoms. Carriers (one mutated, one normal gene) typically do not show symptoms. - Mnemonic: \"Autosomal Recessive\" (AR) 2. Affects 1 in 2000 (Europeans) - Explanation: Prevalent among Europeans, less common in African and Asian populations. - Mnemonic: \"1 in 2000 Europeans\" (1E) 3. More than 1500 Different Mutations of CFTR Gene - Explanation: CFTR gene on chromosome 7 encodes the CFTR protein (chloride channel). Most common mutation is F508del, causing misfolded CFTR protein. - Mnemonic: \"1500+ Mutations\" (1500+) 4. CFTR as a Cyclic AMP Regulated Chloride Channel - Explanation: Regulates chloride ion and water transport across cell membranes. Proper function maintains salt and water balance on epithelial surfaces. - Mnemonic: \"CFTR = Chloride Function\" (CF) ΔF508 Mutation in Cystic Fibrosis 1. CFTR Gene - Explanation: Located on chromosome 7, encodes CFTR protein (chloride channel). - Mnemonic: \"Chromosome 7 = CFTR\" (C7CFTR) 2. ΔF508 Mutation - Explanation: Deletion of phenylalanine at the 508th position causes misfolded protein. Misfolded protein is degraded, reducing functional CFTR at the cell surface. - Mnemonic: \"ΔF508 = Misfolded Protein\" (MP) 3. Consequences of ΔF508 - Explanation: Impaired chloride ion transport, leading to thick, sticky mucus in organs. - Mnemonic: \"Thick Mucus\" (TM) Impact on Health and Treatment - Respiratory Issues: Thick mucus obstructs airways, causing lung infections and reduced lung function. - Mnemonic: \"Respiratory Issues\" (RI) - Digestive Problems: Blockage of pancreatic ducts leads to malabsorption of nutrients. - Mnemonic: \"Digestive Problems\" (DP) - Other Complications: Potential issues in liver and intestines. - Mnemonic: \"Other Complications\" (OC) - Treatment: Symptomatic management, airway clearance, inhaled medications, pancreatic enzyme replacement, CFTR modulators. - Mnemonic: \"Treatment Management\" (TM) Mutations Outside the Coding Sequence of the Gene 1. Promoter - Effect of Mutation: May increase or decrease the rate of transcription. - Mnemonic: \"Promoter = Transcription Rate\" (PTR) 2. Transcriptional Regulatory Element/Operator Site - Effect of Mutation: May alter the regulation of transcription. - Mnemonic: \"Transcriptional Regulator = Transcription Control\" (TRTC) 3. Splice Junctions - Effect of Mutation: May alter the ability of pre-mRNA to be properly spliced. - Mnemonic: \"Splice Junction = Splice Function\" (SJSF) 4. Translational Regulatory Element - Effect of Mutation: May alter the ability of mRNA to be translationally regulated. - Mnemonic: \"Translational Regulator = Translation Control\" (TRTC) 5. Intergenic Region - Effect of Mutation: Not as likely to affect gene expression. - Mnemonic: \"Intergenic Region = Minimal Effect\" (IRME) Repetitive DNA Sequences 1. Microsatellites - Definition: Short, repetitive DNA sequences (1-6 base pairs) repeated in tandem. - Location: Found throughout the genome, often within or near genes. - Function: Used in genetic mapping, population studies, and forensic analysis due to high variability. - Mnemonic: \"Microsatellites = Short Repeats\" (MSR) 2. Minisatellites - Definition: Longer repetitive sequences (10-100 base pairs) repeated in tandem. - Location: Commonly found in telomeres and other chromosomal regions. - Function: Used in genetic fingerprinting and paternity testing due to high variability. - Mnemonic: \"Minisatellites = Longer Repeats\" (MLR) 3. Short Interspersed Nuclear Elements (SINEs) - Definition: Short, non-coding repetitive sequences (100-300 base pairs). - Characteristics: Transposable elements that can move within the genome. - Function: Regulate gene expression and contribute to genetic diversity. Example: Alu element. - Mnemonic: \"Short Interspersed = Regulatory Movers\" (SIRM) 4. Long Interspersed Nuclear Elements (LINEs) - Definition: Longer repetitive sequences (1,000-7,000 base pairs). - Characteristics: Transposable elements capable of encoding proteins like reverse transcriptase. - Function: Contribute to genomic variation and evolution, influence gene structure and function. - Mnemonic: \"Long Interspersed = Variable Movers\" (LIVM) 5. Satellite DNA - Definition: Large blocks of repetitive sequences (more than 100 base pairs) found in specific genome regions like centromeres and telomeres. - Characteristics: Exists in various lengths, classified into \"alpha-satellite\" and \"mini-satellite.\" - Function: Crucial for chromosome structure and stability, plays roles in cell division. - Mnemonic: \"Satellite = Chromosome Stability\" (SCS) 6. Triplet Repeats - Definition: Sequences of three nucleotides repeated multiple times (e.g., CAG, CTG). - Characteristics: Found within or near genes, associated with certain genetic disorders. - Function: Contribute to genetic variation, expanded repeats linked to diseases like Huntington\'s disease and certain types of muscular dystrophy. - Mnemonic: \"Triplet Repeats = Disease Links\" (TRDL) Huntington's Disease (HD) - Triplet Repeat 1\. Autosomal Dominant - Inheritance: Only one copy of the mutated gene from an affected parent is needed to cause the disease. - Mnemonic: \"Autosomal Dominant HD\" (ADHD) 2\. IT15 Gene and Huntingtin Protein - Gene: IT15 gene encodes the huntingtin protein (3144 amino acids). - Function: Believed to play a role in neuronal function, intracellular transport, and cell survival. - Mnemonic: \"IT15 = Huntingtin Protein\" (IHP) 3\. Prevalence - Statistic: Affects approximately 1 in 20,000 individuals. - Mnemonic: \"1 in 20K HD\" (20KHD) 4\. CAG Triplet Repeat Expansion - Genetic Mutation: Expansion of CAG triplet repeat within the IT15 gene. - Normal Range: Up to 26 CAG repeats. - Intermediate Range: 27-35 CAG repeats, generally asymptomatic. - Reduced Penetrance: 36-39 CAG repeats, may or may not develop symptoms. - Pathogenic Range: More than 39 CAG repeats, leading to Huntington's disease. - Mnemonic: \"CAG Triplet Expansion = HD\" (CTEHD) 5\. Late-Onset - Explanation: Symptoms typically appear between ages 30 and 50, but can vary widely. - Mnemonic: \"Late-Onset HD\" (LOHD) 6\. Anticipation - Explanation: Successive generations may exhibit earlier onset and more severe symptoms due to the instability of the CAG repeat. - Mnemonic: \"Anticipation in Generations\" (AG) Genetics 4 BLURT! 4^1^ Genetic Basis of Sex Determination -- describe the genetic basis of sex determination; what are the 4 characteristics of sex determination? = Human Karyotype, Female Chromosomes (46,XX), Male Chromosomes (46,XY), Hemizygous Condition in Males. 1. Human Karyotype -- what is the human karyotype? What does it consist of? - Karyotype: Complete set of chromosomes in an individual, organized in pairs. Humans have 23 pairs, totaling 46 chromosomes. - Sex Chromosomes: The 23rd pair differs between males and females: - Females: Two X chromosomes (46,XX). - Males: One X and one Y chromosome (46,XY). - Mnemonic: \"23 pairs, Sex Chromosomes\" 2\. Female Chromosomes (46,XX) - XX Configuration: Females inherit one X chromosome from each parent. - Genetic Expression: Two copies of genes located on the X chromosome can lead to the expression of traits that may not be expressed in males. - Mnemonic: \"XX = Female Traits Expressed\" 3\. Male Chromosomes (46,XY) - XY Configuration: Males inherit the X chromosome from their mother and the Y chromosome from their father. - Sex-Determining Region Y (SRY): The Y chromosome contains the SRY gene, which triggers male sex determination, leading to the development of male characteristics. - Mnemonic: \"XY = SRY Gene Triggers Maleness\" 4\. Hemizygous Condition in Males - Hemizygous: Presence of only one copy of a gene instead of two. Males are hemizygous for the X chromosome. - Implications of Hemizygosity: Genes on the X chromosome will be expressed regardless of whether they are dominant or recessive. This makes males more susceptible to X-linked recessive conditions like hemophilia and color blindness. - Mnemonic: \"Hemizygous = Males, Susceptible to X-linked Conditions\" What Causes Maleness and Femaleness? 1. XX = Female: The presence of two X chromosomes causes femaleness. 2. X- = Male: The presence of a single X and a Y chromosome causes maleness. 3. Chromosomal Variations: Observations from Klinefelter and Turner syndromes help understand sex determination. Klinefelter Syndrome 1. Definition - Klinefelter Syndrome (KS): A genetic condition where males have an extra X chromosome, resulting in a total of 47 chromosomes instead of the usual 46. - Mnemonic: \"XXY = Extra X Chromosome in Males\" (XXYECM) 2. Genetic Basis - Chromosome Configuration: Males typically have one X and one Y chromosome (46,XY), but in KS, they have an extra X chromosome (47,XXY). - Causes: The extra X chromosome is a result of a random error during the formation of reproductive cells. - Mnemonic: \"Random Error in Gametes\" (REG) 3. Symptoms - Physical Characteristics: - Tall Stature: Often taller than average with long arms and legs. - Reduced Muscle Mass: Lower muscle tone and strength. - Small Testes: Underdeveloped testes leading to lower testosterone levels. - Gynecomastia: Enlarged breast tissue. - Reduced Facial and Body Hair: Less hair growth. - Developmental and Cognitive: - Learning Difficulties: Challenges with reading, writing, and spelling. - Speech and Language Issues: Potential speech delays and difficulties. - Social Development: May experience social awkwardness and difficulty forming relationships. - Mnemonic: \"Tall Structure, Reduced Muscle, Gynecomastia, Reduced Hair, Learning Difficulties\" (TSRM GRH LD) 4. Diagnosis - Karyotyping: A blood test to analyze chromosomes and confirm the presence of an extra X chromosome. - Physical Examination: Assessment of physical traits and symptoms. - Mnemonic: \"Karyotype Test\" (KT) 5. Treatment - Testosterone Replacement Therapy: To address low testosterone levels and help develop male characteristics. - Speech and Physical Therapy: To support language and motor skills. - Psychological Support: Counselling to address emotional and social challenges. - Mnemonic: \"Testosterone, Speech, Psychological\" (TSP) 6. Prognosis - Life Expectancy: Generally normal, but with potential health issues like osteoporosis and cardiovascular problems. - Quality of Life: Many individuals with KS lead independent and fulfilling lives with appropriate support and treatment. - Mnemonic: \"Normal Life Expectancy\" (NLE) Turner Syndrome 1. Karyotype and Chromosomal Composition - Karyotype: 45,XO; only one X chromosome and no second sex chromosome. - Phenotypically Female: Exhibits female physical characteristics. - Mnemonic: \"45XO = One X Chromosome\" (45XOX) 2. Prevalence - Incidence: 1 in every 2000 to 6000 female births. - Mnemonic: \"1 in 2000-6000\" (2000-6000) 3. Physical Characteristics - Short Stature: Often shorter due to growth hormone deficiencies. - Malformed Features: Webbed neck, high palate, small jaw (micrognathia). - Mnemonic: \"Short Stature, Malformed Features\" (SSMF) 4. Congenital Anomalies - Heart Defects: Coarctation of the aorta, bicuspid aortic valve. - Kidney Abnormalities: Horseshoe kidney. - Mnemonic: \"Heart Anomalies, Kidney Anomalies\" (HAKA) 5. Reproductive System - Ovarian Development: Female external genitalia and internal ducts, but rudimentary or absent ovaries. - Ovarian Failure: Primary ovarian insufficiency leading to hormone deficiency. - Infertility: Often unable to conceive naturally. - Mnemonic: \"Ovarian Failure, Infertility\" (OFI) 6. Cognitive Function - Intelligence: Generally normal, but may have specific learning disabilities, particularly in spatial reasoning and mathematics. - Mnemonic: \"Normal Intelligence, Learning Disabilities\" (NILD) 47,XXX Syndrome - Karyotype: 47,XXX; presence of three X chromosomes. - Female Differentiation: Results in female characteristics. - Symptoms: Frequently normal, but some may have underdeveloped secondary sex characteristics, sterility, and mental retardation. - Mnemonic: \"47XXX = Female Characteristics, Symptoms Variable\" (FCSV) 47,XYY Condition (XYY Syndrome) 1. Karyotype - 47,XYY: Presence of an extra Y chromosome, resulting in 47 chromosomes total. - Male Characteristics: Genetically male. - Mnemonic: \"47XYY = Extra Y Male\" (EY M) 2. Height - Increased Stature: Tend to be over 6 feet tall. - Mnemonic: \"Tall Stature\" (TS) 3. Cognitive Function - Subnormal Intelligence: Some may have subnormal intelligence, with variability. - Learning Difficulties: Increased prevalence of learning disabilities, particularly in language and reading skills. - Mnemonic: \"Learning Difficulties, Subnormal Intelligence\" (LDSI) 4. Behavioral Characteristics - Behavioral Issues: Potential for behavioral problems, including aggression or impulsivity. - Emotional and Social Functioning: Challenges with social interactions and emotional regulation, with variability. - Mnemonic: \"Behavioral Issues, Emotional Social Challenges\" (BI ESC) Nondisjunction in Meiosis 1. Normal Chromosome Separation in Meiosis - Meiosis I: Homologous chromosomes separate into two daughter cells. - Meiosis II: Sister chromatids separate into four unique gametes, each containing one copy of each chromosome. - Mnemonic: \"Normal Separation = Meiosis I and II\" (NS MI II) 2. Nondisjunction in Meiosis I - Event: Both homologous chromosomes move to the same daughter cell. - Outcome: Two gametes with an extra chromosome (trisomy) and two gametes lacking that chromosome (monosomy). - After Fertilization: - Trisomic Zygote (2n + 1): Contains an extra chromosome. - Monosomic Zygote (2n - 1): Missing one chromosome. - Mnemonic: \"Nondisjunction I = Trisomy, Monosomy\" (NI TM) 3. Nondisjunction in Meiosis II - Event: Sister chromatids fail to separate. - Outcome: One gamete with an extra chromosome (trisomy), one gamete lacking a chromosome (monosomy), and two normal gametes. - After Fertilization: - Trisomic Zygote (2n + 1): Contains an extra chromosome. - Monosomic Zygote (2n - 1): Missing one chromosome. - Normal Zygote (2n): Correct number of chromosomes. - Mnemonic: \"Nondisjunction II = Variable Outcomes\" (NII VO) Genetic Determination of Sex in Humans 1. Y Chromosome Determines Maleness - SRY Gene: The presence of the Y chromosome and its SRY gene triggers male sex determination. - Chromosome Configuration: - 46,XY: Individual develops as male. - 46,XX: Individual develops as female. - Mnemonic: \"SRY = Male Determination\" (SMD) 2. Heterogametic Males - Definition: Males have two different sex chromosomes (XY), while females have two identical X chromosomes (XX). - Mnemonic: \"Heterogametic Males = XY\" (HM XY) 3. Size and Gene Content - X Chromosome: - Larger and gene-rich (900-1,400 genes). - Involved in brain development, immunity, and reproduction. - Mutations in X-linked genes can lead to various genetic disorders. - Y Chromosome: - Smaller with approximately 75 functional genes. - Primarily involved in male sex determination and spermatogenesis. - Contains a pseudoautosomal region (PAR) for pairing during meiosis. - Mnemonic: \"X = Larger, Gene-rich, Y = Smaller, Functional\" (XLG YSF) Visual Representation of Nondisjunction in Meiosis The image shows a diagram of the process of meiosis, highlighting the stages of normal chromosome separation and the events of nondisjunction in both Meiosis I and Meiosis II: 1. Normal Chromosome Separation in Meiosis: - Meiosis I: Homologous chromosomes separate into two daughter cells. - Meiosis II: Sister chromatids separate into four unique gametes, each containing one copy of each chromosome. 2. Nondisjunction in Meiosis I: - Event: Both homologous chromosomes move to the same daughter cell. - Outcome: Two gametes with an extra chromosome (trisomy) and two gametes lacking that chromosome (monosomy). - After Fertilization: - Trisomic Zygote (2n + 1): Contains an extra chromosome. - Monosomic Zygote (2n - 1): Missing one chromosome. 3. Nondisjunction in Meiosis II: - Event: Sister chromatids fail to separate. - Outcome: One gamete with an extra chromosome (trisomy), one gamete lacking a chromosome (monosomy), and two normal gametes. - After Fertilization: - Trisomic Zygote (2n + 1): Contains an extra chromosome. - Monosomic Zygote (2n - 1): Missing one chromosome. - Normal Zygote (2n): Correct number of chromosomes. Y Chromosome and the SRY Evolution of the Y Chromosome 1. Genetic Homology: The Y chromosome was once homologous to the X chromosome. 2. Sex-Determining Gene: Acquired the SRY gene. 3. Male Genes Cluster: Genes beneficial to males accumulated near SRY. 4. Suppressed Recombination: Recombination with the X chromosome was suppressed. 5. Lack of Recombination: Distinct alleles on the Y chromosome are not exposed to natural selection. - Mnemonic: \"SRY = Male Determination\" (SMD) Development of Sex Organs 1. Gonads Undifferentiated at 7 Weeks: Potential to develop into either ovaries or testes. 2. Default Development is Female: In the absence of male signals, the pathway leads to the formation of ovaries. 3. Y Chromosome and Male Hormones: Presence of Y chromosome and SRY gene triggers male hormone production, leading to the development of testes. - Mnemonic: \"Default Development = Female\" (DDF) Y Chromosome and Male Development 1. SRY Activation: At 6-8 weeks, SRY gene activates in XY embryos. 2. Testes Formation: SRY triggers the development of testes. 3. Transcription Factor: SRY binds and bends DNA, regulating gene expression. 4. SOX9 Transcription: SRY upregulates SOX9, crucial for testes development. 5. Precursor Cells: SOX9 differentiates precursor cells into Sertoli and Leydig cells. 6. Inhibiting Substance: Sertoli cells produce AMH, preventing female reproductive development. - Mnemonic: \"SRY = Sertoli Cells Activate Testes\" (SCAT) SRY Gene and Its Role in Sex Determination 1. SRY Translocation: SRY on another chromosome can result in an XX male. 2. Missing SRY: Absence on Y chromosome can result in an XY female. 3. Dependence on Other Genes: SRY relies on other genes like SOX9 and testosterone pathways for male development. 4. Testosterone Receptor Mutation: Mutation in testosterone receptors can lead to AIS, where genetically XY individuals develop female secondary sexual characteristics. - Mnemonic: \"SRY = Requires Genes\" (SRG) X Chromosome Inactivation Dosage Compensation - Balances the dose of X chromosome gene expression in females and males: All but one of the X chromosomes is inactivated. - Mnemonic: \"Dosage Compensation\" (DC) Barr Bodies 1. Definition: The inactive X chromosome in a female cell, highly condensed, observed in stained interphase cells. 2. Random Inactivation: Either the maternally or paternally derived X chromosome is randomly inactivated early in embryonic development. All cellular descendants inherit the same inactivated chromosome. 3. Purpose: Ensures that females do not produce twice the amount of X-linked gene products compared to males. Results in equal dosage of X-linked gene expression between males and females. - Mnemonic: \"Barr Bodies\" (BB) Barr Bodies and X-Chromosome Inactivation 1. What are Barr Bodies: Inactive X chromosome, highly condensed, seen in stained interphase cells. Manages gene dosage by inactivating one X chromosome in females. 2. Random X-Chromosome Inactivation: Occurs randomly in early embryonic development. Same X chromosome remains inactive in all descendant cells. 3. Why X-Inactivation Occurs: To prevent overproduction of X-linked gene products in females. 4. Barr Bodies in Genetics: - Turner Syndrome (45,X): No Barr bodies. - Klinefelter Syndrome (47,XXY): One Barr body. - Mnemonic: \"Barr Bodies = X Inactivation\" (BB XI) Complications and Related Genetic Disorders Turner Syndrome (45,XO) - Not entirely normal due to the lack of a second X chromosome, leading to developmental abnormalities. Some genes escape X-inactivation and need to be in two copies for normal development. - Mnemonic: \"Turner = No Second X\" (TNSX) Triple (47,XXX) or Tetra (48,XXXX) X Chromosomes - Mild to moderate developmental and intellectual challenges. Not all genes on extra X chromosomes are inactivated, leading to overexpression of some genes. - Mnemonic: \"Triple/Tetra X = Overexpression\" (TXO) Klinefelter Syndrome (47,XXY) - Traits like tall stature, infertility, reduced testosterone, and learning difficulties. Extra X chromosome contributes to phenotype as some genes escape inactivation, causing feminized characteristics. - Mnemonic: \"Klinefelter = Extra X Effects\" (KEE) The Mechanism of X Inactivation X Chromosome Pairing and Xic Locus - Pairing: Before X inactivation, the two X chromosomes align briefly at the X-inactivation center (Xic). - Xic Locus: Contains critical genetic information to initiate X inactivation. - Mnemonic: \"Xic = Inactivation Center\" (XIC) Role of the Xic and XIST Gene - Xic: Major control center for X inactivation, regulating which X chromosome will be inactivated. - XIST Gene: Located within the Xic, transcribes RNA that does not code for any protein but directly silences the X chromosome. - Mnemonic: \"XIST = Silencing RNA\" (XISR) Mechanism of Inactivation via RNA Coating - XIST RNA: Coats the X chromosome, contributing to its condensation and inactivation, turning it into a Barr body. - Permanent Change: Inactivated X chromosome remains silent throughout the organism\'s lifetime, with all descendant cells maintaining the same inactivated X chromosome. - Mnemonic: \"XIST RNA = Condensation and Inactivation\" (XRCI) X-Linked Inheritance 1\. Location of the Gene - Definition: The gene causing a trait or disorder is located on the X chromosome. - Mnemonic: \"X-Linked Genes\" (XLG) 2\. Females and X-Linked Recessive Traits - Two X Chromosomes: Females have two copies of every X-linked gene. - Recessive Trait Masked: If a recessive trait is on one X chromosome, the dominant allele on the other can mask it, making females typically carriers. - Mnemonic: \"Females X-Linked Recessive Carriers\" (FXRC) 3\. Males and X-Linked Recessive Traits - One X Chromosome: Males have one X and one Y chromosome. - Express Recessive Trait: A recessive trait on the X chromosome will be expressed because there\'s no second X chromosome to mask it. - Mnemonic: \"Males X-Linked Recessive Express\" (MXRE) 4\. Carrier Females - One Recessive Mutation: Carrier females have one copy of a recessive mutation on one X chromosome and a normal allele on the other. - Variable Expression: X chromosome inactivation can lead to varying clinical expression in carrier females, with some cells expressing the recessive allele and others the normal allele. - Mnemonic: \"Carrier Females Variable Expression\" (CFVE) Key Points - X-Linked Traits: Carried on the X chromosome. - Females: Typically carriers if they have a recessive mutation on one X chromosome, masked by a dominant allele on the other. - Males: Will express the trait with a recessive X-linked mutation on their only X chromosome. - Carrier Females: May show mild symptoms due to X-inactivation, varying the expression of X chromosomes in different cells. Genetics 5 BLURT! 5^1^ History and Discovery - Early 20th Century Discoveries: Identified genetic disorders affecting metabolism. - Mnemonic: \"IEM = Early Discoveries\" (IED) Detailed Examples of IEMs 1. Galactosaemia: Inability to metabolize galactose. 2. Albinism: Lack of melanin production. 3. Alkaptonuria: Accumulation of homogentisic acid. 4. Phenylketonuria: Inability to metabolize phenylalanine. 5. Maple Syrup Urine Disease: Inability to break down certain amino acids. 6. Glycogen Storage Disorders: Issues with glycogen metabolism. 7. Lysosomal Storage Disorders: Dysfunctional lysosomal enzymes. - Mnemonic: \"Great Alchemist Applies Potions Mixed Globally\" (GAAPMG) What is a Metabolic Pathway? - Definition: A series of biochemical reactions occurring within cells. - Process: - Principal substrate is modified step-by-step to form an end product. - End Product Uses: - Immediately used. - Initiates another metabolic pathway. - Stored. - Each step is catalyzed by enzymes. - Mnemonic: \"Metabolic Pathway Explained\" (MPE) Inborn Errors of Metabolism (IEMs) - Definition: A large class of inherited genetic diseases involving metabolism. - Prevalence: Individually rare but significant combined (1:1400 births, 15% of single gene disorders). - Genetic Basis: Majority are single gene defects encoding enzymes. - Consequences: - Abnormal accumulation of substrate. - Toxic to cell. - Interfere with normal cell function. - Decrease ability to synthesize essential compounds (energy deprivation). - Mnemonic: \"IEM = Rare Genetic Disorders\" (RGC) Groups of IEMs (Classified by Metabolite/Organelle) 1. Protein Metabolism - Amino acidopathies. - Organic acidopathies. - Urea cycle defects. 2. Carbohydrate Metabolism - Glycogen storage disorders. 3. Other Categories - Fatty acid. - Mitochondrial. - Peroxisomal. - Lysosomal storage. - Mnemonic: \"Protein, Carbohydrate, Others\" (PCO) Clinical Manifestations of IEMs - Symptoms: - Developmental delay, mental retardation, seizures. - Failure to thrive, poor feeding. - Vomiting, dehydration, acidosis. - Peculiar odor. - Repeated hospitalizations, coma. - Onset: - Many expressed in neonatal period & first year. - Others may not appear until adulthood. - Mnemonic: \"Distinctive Symptoms, Varied Onset\" (DSVO) Defective Proteins of IEMs - Protein Defect: Typically in enzyme, leading to blocking of a metabolic pathway (e.g., glycogen breakdown). Accumulation of Substrate 1. Substrate Not Converted to Normal Product: Accumulates to toxic levels. 2. Substrate Side-Channelled: Converted to another metabolite. 3. Minor Metabolite Accumulates: Reaches damaging levels (e.g., galactose in galactosaemia). - Mnemonic: \"Accumulation Occurs\" (AO) Galactosaemia - Excess Galactose Conversion: Galactose converted to galactitol causing: - Osmotic Damage: Lens fibers leading to cataracts. - Liver Failure and Developmental Problems: Can be fatal in infants. - Classical Galactosaemia: Mutations in galactose-1-phosphate uridyl transferase. - Milder Forms: Mutations in galactokinase or epimerase. - Mnemonic: \"Galactose Toxic Conversion\" (GTC) Diagnosis and Treatment of Galactosaemia - Diagnosis: - Heel prick at birth - reduced GALT enzyme in blood. - Followed by genetic testing. - Treatment: - Elimination of galactose from diet (dairy). - Soya milk. - Supplement calcium and Vitamin D. - Speech and occupational therapy. - Eye tests, neurological assessments, bone density screening. - Prognosis: Normal life expectancy if caught early. - Mnemonic: \"Diagnosis, Treatment, Prognosis\" (DTP) Product Deficiency - Reduction in Crucial Product: Affects cell function. - Examples: Albinism, congenital hypothyroidism, congenital adrenal hyperplasia, vitamin D-dependent rickets. - Mnemonic: \"Reduction Affects Cell\" (RAC) Albinism - Ocular Albinism: Pale blue eyes. - Oculocutaneous Albinism: Affects eyes, skin, hair. - Symptoms: Photosensitivity and skin problems. - Developmental Needs: Melanin needed for correct optical system development. - Mnemonic: \"Ocular Oculocutaneous Photosensitivity\" (OOP) Mutations of Non-Enzyme Proteins 1. Defective Membrane Receptors - Example: LDL receptors - familial hypercholesterolaemia. - Mnemonic: \"Defective Membrane Receptors\" (DMR) 2. Defective Transport Proteins - Example: Chloride transport - cystic fibrosis. - Mnemonic: \"Defective Transport Proteins\" (DTP) 3. Hartnup Disease - Symptoms: Pellagra-like skin eruption (low nicotinamide), poor absorption of non-polar amino acids like tryptophan. - Treatment: Nicotinamide supplements, tryptophan-rich diet. - Mnemonic: \"Hartnup = Poor Amino Acids\" (HPAA) Inborn Errors of Metabolism (IEMs) Inheritance Patterns 1. Autosomal Recessive - Most common. - Defect in enzyme or transport protein. - Mnemonic: \"Autosomal Recessive Common\" (ARC) 2. X-Linked Recessive - Example: Hunter disease (lysosomal). - Mnemonic: \"X-Linked Hunter\" (XH) 3. Mitochondrial - Some IEMs involve mitochondrial DNA. - Mnemonic: \"Mitochondrial Involvement\" (MI) 4. Dominant Defects - Few IEMs are caused by dominant gene interactions. - Mnemonic: \"Dominant IEMs Few\" (DIF) Specific Examples of IEMs 1. Alkaptonuria 2. Phenylketonuria 3. Maple Syrup Urine Disease 4. Glycogen Storage Disorders - Mnemonic: \"Alkaptonuria, PKU, Maple Syrup, Glycogen\" (APMSG) Historical Insight Sir Archibald Garrod (1857-1936) - Pioneer in the field of IEMs. - Seminal paper in 1923. - Physician at King's College London. - Key Discoveries: - Studied urine biochemistry. - Found abnormal uric acid in gout patients\' urine. - Proposed that some diseases are \"inborn errors of metabolism.\" - Suggested "one gene produces one protein." - Molecular basis of inheritance. - Mnemonic: \"Sir Archibald Garrod = IEM Pioneer\" (SAG IEM) Alkaptonuria - Symptoms: - Urine turns black when exposed to air. - Arthritis and joint pain develop later. - Brown pigmentation in cartilage and connective tissue. - Inheritance: Autosomal recessive. - Cause: Reduced activity of one metabolic step. - Treatment: - Symptom management. - Low protein diet. - NSAIDs and physical therapy for joint pain. - Nitisinone for hereditary tyrosinemia type 1. - Mnemonic: \"Alkaptonuria = Black Urine\" (ABU) Phenylketonuria (PKU) Dr. Ivar Asbjørn Følling (1888-1973) - Identified PKU. - Considered a major scientist despite not receiving a Nobel Prize. - Signs and Symptoms of PKU: - Fair complexion and blue eyes. - Significantly reduced head size. - Mental retardation. - Seizures. - Jerky arms and legs. - Tremors. - Hyperactivity. - Unpleasant musty odor. - Mnemonic: \"PKU = Fair, Blue Eyes, Mental Retardation\" (PFMR) Classic PKU Prevalence - UK: 1 in 14,000 live births. - Turkey: 1 in 2,600 live births. - Mnemonic: \"PKU in UK 1/14000, Turkey \*\*1/2600\" (PUKT) Cause - Mutation in PAH Gene: Encodes hepatic enzyme phenylalanine hydroxylase. - Effect: Inability to catalyze the breakdown of phenylalanine into tyrosine. - Inheritance: Autosomal recessive. - Mnemonic: \"PAH Gene Mutation Causes Recessive PKU\" (PCR) Metabolic Pathway for Phenylalanine - Phenylalanine (Phe) Accumulation: Due to lack of phenylalanine hydroxylase. - Conversion: Phe converted into phenylpyruvate (phenylketone). - Detection: Detected in urine (musty smell). - Inhibition: Inhibits pyruvate decarboxylase, leading to decreased myelin synthesis. - Physical Traits: Fair hair and eyes due to affected melanin production. - Mnemonic: \"Phe Accumulation Detected in Urine\" (PADU) PAH Gene - Location: 12q22-12q24.1. - Mutations: Over 400 mutations detected, leading to a wide spectrum of disease severity. - Mnemonic: \"PAH Gene on 12q22\" (PAH 12q22) Malignant PKU - Cause: Phe accumulates due to lack of cofactor tetrahydrobiopterin. - Effect: Enzyme required to form cofactor is deficient. - Frequency: Very rare. - Mnemonic: \"Malignant PKU = Lacks Cofactor\" (PKU LC) Diagnosis of PKU - Heel Prick Test: Performed 2-7 days after birth using Guthrie cards. - Procedure: - Measures blood level of phenylalanine. - Blood transferred to agar plate with specific strain of Bacillus subtilis that requires phenylalanine for growth. - Presence of a halo of bacterial growth indicates positive test for phenylalanine. - Additional Methods: Immunoassays, tandem mass spectrometry. - Diagnostic Levels: Blood phenylalanine levels 4-10 mg/dL (normal levels 1-2 mg/dL). - Mnemonic: \"Heel Prick Test for PKU\" (HPT PKU) Treatment of PKU - Diet: Low in phenylalanine; avoid eggs, milk. - Nutrasweet: Avoid (contains aspartame, an ester of phenylalanine). - Lofenalac: Safe protein replacement milk powder for PKU patients. - Biopterin: Supplement for malignant PKU. - Mnemonic: \"PKU Diet: Low Phenylalanine\" (LP) Maple Syrup Urine Disease - Breakdown Issue: Inability to break down leucine, isoleucine, valine; leads to blood buildup. - Severe Form: Can damage brain during physical stress (infection, fever, malnutrition). - Mild Form: Fluctuating; physical stress can cause intellectual disability, high leucine levels. - Mnemonic: \"Maple Syrup Urine Disease = Amino Acid Breakdown Issue\" (AABI) Inborn Errors of Glucose Metabolism - Glucose Usage: 75% by brain; rest by erythrocytes, skeletal muscle, heart muscle. - Sources: Directly from diet or via gluconeogenesis (amino acids, lactate). - Storage: Soluble in body fluids or stored as glycogen. - Mnemonic: \"Glucose Metabolism Usage\" (GMU) Glycogen Structure - Polymer of glucose residues linked by α-(1,4)- and α-(1,6)-glycosidic bonds. - Main Storage: Liver (10% of weight); skeletal muscle (not available to other tissues due to lack of glucose-6-phosphatase). - Mnemonic: \"Glycogen = Glucose Polymer in Liver\" (GPL) Glycogen Synthesis 1. UDP-Glucose Formation: UDP-glucose pyrophosphorylase forms UDP-glucose from G-1-P. 2. Addition to Glycogen: Glycogen synthetase adds UDP-glucose. 3. Branching: Branching enzyme (amylo (1,4-1,6)-transglycosylase) transfers 6/7 glucose residues to a chain of at least 11 residues. - Mnemonic: \"Glycogen Synthesis = Form Add Branch\" (FAB) Glycogenolysis: Accessing Stores 1. Removal: Glycogen phosphorylase removes single glucose residues from α-(1,4) linkages. 2. End-Product: Glucose-1-phosphate, converted to glucose-6-phosphate by phosphoglucomutase. - Mnemonic: \"Glycogen Breakdown = Remove Convert\" (RC) Debranching of Glucose 1. Enzyme: Debranching enzyme (glucan transferase) cleaves α-1,6 linkages. 2. Transferase: Removes 3 terminal glucose residues, attaches to free C-4 end of another branch. 3. Glucosidase: Removes glucose in α-(1,6) linkage at branch. - Mnemonic: \"Debranch = Cleave, Remove, Glucose\" (CRG) Glycogen Storage Diseases (GSD) - Issue: Inability to degrade glycogen causes pathological cell engorgement. - Effects: Functional loss of glycogen as cell energy source and blood glucose buffer. - Prevalence: Rare (1:20,000 -- 43,000 live births) but dramatic effects. - Mnemonic: \"GSD = Inability to Degrade Glycogen\" (IDG) 2 Primary Groups of GSD 1. Liver Glycogen Homeostasis Defects: Hepatomegaly, hypoglycemia, cirrhosis. 2. Muscle Glycogen Homeostasis Defects: Skeletal and cardiac myopathies, energy impairment. - Notable Disease: Pompe disease (Type II GSD -- glycogen in lysosomes of muscle cells). - Mnemonic: \"GSD = Liver Muscle Defects\" (LMD) Types of GSDs 1. GSD 0a - Enzyme: Liver isozyme of glycogen synthase (GYS2) - Organ: Liver - Symptoms: Hypoglycemia, early death, hyperketonia, low blood lactate and alanine - Mnemonic: \"0a Liver Synthase GYS2\" (0aLSG) 2. GSD Ia (von Gierke) - Enzyme: Glucose-6-phosphatase - Organs: Liver, kidney - Symptoms: Hepatomegaly, hypoglycemia, kidney failure, thrombocyte dysfunction, gout, growth failure - Mnemonic: \"Ia Liver-Kidney G6Pase\" (IaLKG) 3. GSD Ib - Enzyme: Microsomal (ER) glucose-6-phosphate translocase (G6PT1) - Organ: Liver - Symptoms: Similar to GSD Ia, plus neutropenia, bacterial infections - Mnemonic: \"Ib Liver G6PT1\" (IbLG) 4. GSD Ic - Enzyme: Microsomal Pi transporter - Organ: Liver - Symptoms: Similar to GSD Ia - Mnemonic: \"Ic Liver Pi\" (IcLP) 5. GSD II (Pompe) - Enzyme: Lysosomal acid α-glucosidase - Organs: Skeletal, cardiac muscle - Symptoms: Muscle weakness, heart failure (infantile form - death by 2; juvenile form - myopathy; adult form - muscular dystrophy-like) - Mnemonic: \"II Muscle α-Glucosidase\" (IIMaG) 6. GSD III (Cori or Forbes) - Enzyme: Liver and muscle debranching enzyme - Organs: Liver, skeletal, cardiac muscle - Symptoms: Infant hepatomegaly, myopathy, hyperlipidemia - Mnemonic: \"III Debranching Liver-Muscle\" (IIIDLM) 7. GSD IV (Andersen) - Enzyme: Branching enzyme - Organs: Liver, muscle - Symptoms: Hepatosplenomegaly, cirrhosis, failure to thrive, death \