Biology - Mendel & Pedigrees

for the secod midterm or whatever brah

Autopolyploidy

• Extra sets of chromosomes derived from the same species caused by accidents in mitosis or meiosis.

Colchicine

• Binds tubulin.

• Inhibits tubulin polymerization. 

• Disrupts spindle formation. 

• Used by plant breeders to induce polyploidy. 

• Also used as medicine (i.e. for gout).

Hybridization (Allopolyploidy)

• Changes in chromosome numbers can create stable species in plants. 

• Wild cabbage (Brassica oleracea) has many cultivars, e.g. Broccoli and Cauliflower. 

Allopolyploidy

• A hybrid plant species that is derived from two or more species, containing two or more copies of each original genome. 

Triploid Seedless Plants

• Even-numbered polyploid plants are often bigger than their diploid counterparts.

• Odd-numbered ploidy is often associated with sterility.

• This is because homologous chromosomes cannot pair properly, and segregation would be uneven.

• Without meiosis, seed production is aborted.

Propagating Sterile Triploids

• To propagate such sterile plants:

  • Cuttings can be grown asexually (e.g. banana).

  • Tetraploid plant can be crossed to diploid plant to create triploid seeds (e.g. watermelon).

Cavendish Banana

• Global industry worth $120 billion per year.

• The Cavendish is triploid and sterile.

• Trees are propagated asexually through cloning.

• Genetic uniformity makes crops highly vulnerable.

Cavendish Crisis

• Infected by Sigatoka complex (three ascomycete fungi).

• Weekly fungicide sprays are required on most plantations.

• Fungicide costs: ~$1,000 per hectare yearly (~35% of production).

• Fungal resistance is increasing, threatening global extinction of Cavendish bananas.

Endoreplication & Endopolyploidy

• Occurs when DNA replication repeats without mitosis or cytokinesis.

• Results in polyploid tissues within an otherwise diploid organism.

• Common in large, specialized cells with high synthetic activity.

• Leads to increased gene expression capacity due to extra DNA copies.

Endoreplication & Endopolyploidy Examples

• Human megakaryocytes: Have enlarged, lobulated nuclei; produce platelets (thrombocytes), which function in blood clotting.

• Drosophila larval salivary glands: Contain polytene chromosomes (up to 1024 copies) forming giant chromosomes; synthesize glue to attach the pupa to solid surfaces.

Chromosomal Aberrations

• Involve missing, extra, or rearranged chromosome regions.

• Caused by two or more DNA strand breaks followed by incorrect repair.

• Lead to abnormal chromosome structures that can disrupt gene function.

• To survive cell division, the altered chromosome must retain a centromere and two telomeres.

Deletions through Double-Strand Breaks

• Two breaks occur within a single chromosome.

• NHEJ (non-homologous end joining) proteins are recruited to repair all broken ends.

• Repair may be imprecise, leading to loss of a DNA fragment.

• Can result in chromosomal rearrangements or deletions.

Chromosome Deletions

• Breaks occur in one or more regions of a chromosome.

• A fragment lacking a centromere is typically lost and degraded.

• Phenotypic severity depends on the size and function of deleted genes.

Deletions - Phenotypic Effects

• Depend on the size and gene content of the deleted region.

• Loss of essential genes disrupts development and cellular function.

• Example: Cri du Chat syndrome — deletion on the short arm of chromosome 5.

• Causes mental deficiencies, facial anomalies, and a catlike cry even with one abnormal chromosome copy.

Terminal Deletion

• Loss of one end of chromosome (chromosomal deletion). 

Interstitial Deletion

• Loss of an internal segment (chromosomal deletion). 

Deletions and Duplications from Incorrect Crossover

• Caused by unequal crossing over between homologous chromosomes.

• Misalignment often happens at repetitive sequences.

• Produces one chromosome with a deletion and another with a duplication.

• Duplications are usually less harmful, and small ones often show no effect.

Tandem Duplication

• Duplicated segment appears next to the original (e.g. AB●CDEFG → ABB●CDEFG).

Insertional (Displaced) Duplication

• Duplicated segment is inserted elsewhere (e.g. AB●CDEFG → AB●CBDEFG).

Reverse Duplication

• Duplicated segment is reversed in orientation (e.g. AB●CDEFG → AB●CDEFFEG).

Intrachromosomal vs Interchromosomal

• Duplication on the same chromosome is intrachromosomal; on a different chromosome is interchromosomal.

Duplication and Evolution

• Add new genes to chromosomes over evolutionary time.

• Enable genetic innovation through extra gene copies.

• Gene families arise from duplication and mutation of ancestral genes.

• Allow one gene copy to maintain function while another diverges and gains new roles

Williams-Beuren Syndrome (WBS) Features

• Small deletion (25–28 genes) on chromosome 7.

• Broad forehead, short nose, full cheeks, wide mouth with full lips.

• Narrow blood vessels → hypertension; short stature and mild to moderate intellectual disability.

Williams-Beuren Syndrome (WBS) Traits

• Overfriendly and hypersocial, with a strong urge to approach strangers.

• High sensitivity to certain sound frequencies (~50 Hz).

• Remarkable musical affinity from an early age.

• Warm, expressive personality despite cognitive challenges.

Genetic Basis of Hypersociability (WBS)

• Dogs, but not wolves, carry mutations in WBS genes that promote hypersocial behavior.

• These mutations parallel traits seen in Williams–Beuren syndrome in humans.

• In mice, induced chromosome deletions in the same region cause hypersociability and other WBS-like features.

Reciprocal Translocations

• Occur from double-strand breaks on two non-homologous chromosomes.

• Involve a balanced exchange of chromosome segments.

• During meiosis, they form quadrivalents, often yielding unbalanced gametes.

Non-Reciprocal Translocation

• Represent a one-way transfer of DNA to a non-homologous chromosome.

• Do not involve an equal exchange of material.

• Are less common than reciprocal translocations.

Inversions

• Occur when a chromosome segment reverses orientation.

• Involve rearrangement of genetic material without gain or loss.

• Usually benign, unless breakpoints disrupt vital genes.

• Two types: pericentric & paracentric.

Pericentric Inversion

• Centromere lies within the inverted region.

• Involves both chromosome arms.

• Can change the relative lengths of chromosome arms

Paracentric Inversion

• Centromere lies outside the inverted region.

• Involves only one chromosome arm.

• May lead to abnormal chromatids during meiosis if crossing over occurs.

Inversions via Double Strand Breaks

Nonhomologous End Joining

• Accidental double strand break → loss of nucleotides due to degradation from ends → end joining → deletion of DNA sequence.

Homologous Recombination

• Accidental double-strand break → loss of nucleotides due to degradation from ends → end processing and homologous recombination → damage repaired accurately using information from sister chromatid. 

Non-Homologous End-Joining (NHEJ)

• Repairs double-strand breaks in chromosomes.

• Ku proteins, conserved from bacteria to humans, bind to the breaks.

• Reattaches DNA fibers, often altering the original sequence.

• Removes damaged nucleotides during repair.

• Predominantly occurs in G1, before DNA replication.

Homologous Recombination (HR)

• Repairs DNA by using the sister chromatid as a template, restoring the original sequence.

• Occurs when a template is available, typically after replication (S phase) but before cell division.

• Effective when daughter strands are still near each other post-replication.

• Used in molecular genetics to introduce specific changes via a supplied “fake” template.

Proteins for HR

• Homologous Recombination requires BRCA1 and BRCA2 proteins. 

Angelina Jolie

• All humans have two copies of BRCA1 per cell.

• Mutations in BRCA1 increase cancer risk, often affecting only one allele in patients.

• Double mastectomy performed in 2013.

• Ovaries and fallopian tubes removed in 2015.

Alleles

• Different forms of a gene that exist at a locus.

• Wild type allele is typically the most commonly found allele in a population.

Variant/Mutant Allele

• Different from wildtype allele.

• May or may not adversely affect gene product.

• May or may not result in detectable phenotype.

Homozygous

• If identical alleles are present on both homologous chromosomes, the organism/cell is said to be _________ for that allele.

• Two wild type alleles on two mutant alleles highlight the same allele, so _____ can be used for both.

• FC/FC and fc/fc.

Heterozygous

• If one allele is wild type and the other allele is not (i.e., a mutant allele), the organism/cell is said to be ________ for that allele. 

• FC/fc.

Allelic Series

• The known mutant alleles for a given gene plus its wild-type allele.

• All alleles of the same gene. 

Wild-Type

• Most common allele in a population and functionally normal. 

Flower Colour (FC) Gene

• Purple flowers: functional protein produced.

• White flowers: no functional protein (absence of pigment).

• Gene named FC for “Flower Color.”

• Functional allele = FC; non-functional allele = fc (both listed when referred to).

Alleles on Structural & Functional Levels

• Different alleles can arise from mutations in various regions of a gene (e.g., promoter, coding region, or intron).

• Structural changes in DNA (mutations) can affect whether a functional protein is produced.

Null Mutations

• No functional protein produced; gene “OFF.”

• m1, m2, m3, and m6. 

Leaky Mutation

• Produces reduced protein activity; gene partially “ON.”

• m4.

Synonymous Mutation

• DNA change does not alter amino acid; no effect on protein function.

• m5.

Silent Mutation

• Mutation with no functional consequence.

• m7. 

FC / FC and fc / fc

• Example of homozygous wild-type and mutant genotypes. 

+/+ and -/-

• General symbols for wild-type and mutant alleles.

FC⁺ / FC⁺ and fc⁻ / fc⁻: “+” and “−”

• Denote wild-type and mutant forms of a specific gene.

• “-” would suggest a complete loss of function.

FC⁺ / FC⁺ and fc¹ / fc¹

• Superscripts identify specific alleles.

• Has partial function and is specified in the scientific paper. 

Uppercase/Lowercase Allele

• Uppercase indicates a dominant allele; lowercase indicates a recessive allele.

Heteroallelic

• Two different mutant alleles. 

• Also called transheterozygous or compound heterozygotes.

Hemizygous

• A situation where a cell/organism has only one copy of a gene/locus/chromosomal region.

Hemizygous

• A condition where a cell or organism has only one copy of a gene, locus, or chromosomal region.

• Example 1: Deletion — the corresponding gene or region is missing on the homologous chromosome.

• Example 2: Naturally single-copy genes — common for genes on X or Y chromosomes in XY individuals.

True-Breeding (Flower Ex)

• When plants consistently produce offspring with the same trait when self-crossed (e.g., white × white → white).

• Occurs when individuals are homozygous for the allele(s) controlling the trait.

Genetic Basis of Traits

• May depend on one gene (FC) or multiple genes (FC, W, GD, HE).

  • Monogenic traits. 

  • Polygenic traits. 

Monogenic Traits

• Controlled by a single gene (often with multiple alleles). 

Polygenic Traits

• Controlled by multiple genes, producing more complex variation.

Dominant Allele

• In a heterozygous organism, its phenotype is expressed even when a recessive allele is present.

• Typically represented by uppercase letters (e.g., A).

• Dominance is relative — it may be observed at the organismal level but not always at the molecular or cellular level.

Recessive Allele

• Its phenotype is masked by the dominant allele in a heterozygote.

• Example: If A is dominant, a is the recessive allele.

• Typically represented by lowercase letters (e.g., a).

• The terms dominant and recessive are always defined in relation to each other.

Complete Dominance

• The dominant allele (FC) completely masks the recessive allele (fc) in heterozygotes.

• Both FC/FC and FC/fc produce the same phenotype (purple petals).

• The fc allele is fully recessive when paired with FC.

• Wild-type alleles are often dominant over their mutant counterparts.

Haplosufficient

• A single functional copy of a gene is enough to produce the wild-type phenotype.

• Deals with a molecular mechanistic view. 

• In FC/fc plants, one working FC allele provides sufficient gene product for normal color (purple petals).

Incomplete Dominance

• Not all alleles show simple dominant/recessive relationships.

• The heterozygote displays an intermediate or blended phenotype between the two homozygotes.

• One functional copy is NOT sufficient for a wild type phenotype.

Four-o’clock Plants

• Cᴿᴱᴰ / Cᴿᴱᴰ: Red petals.

• Cᵂᴴᴵᵀᴱ / Cᵂᴴᴵᵀᴱ: White petals.

• Cᴿᴱᴰ / Cᵂᴴᴵᵀᴱ: Pink petals (intermediate phenotype).

• Heterozygotes show a phenotype midway between both homozygous parents.

Haploinsufficiency

• One functional copy is NOT sufficient for a wild type phenotype.

• One wild type copy is not sufficient to produce a wild type phenotype. Could result in complete or incomplete dominance. 

• More phenotypic difference. 

Codominance I

• Both alleles are fully expressed in the heterozygote, showing traits of both without blending.

• Hbᴬ / Hbᴬ: Normal red blood cells.

• Hbˢ / Hbˢ: Severe anemia, sickled cells.

• Hbᴬ / Hbˢ: Some sickling under low oxygen, generally no anemia.

Sickle Cell Anemia

• Caused by a point mutation in hemoglobin.

• Missense mutation: A → T at position 6 of the beta-globin chain.

• Too inflexible and cannot go through capillaries/BVs.

Hemoglobin A

• Tetramer.

• Two different genes that encode β-chain and α-chain.

Hb^s

• Hbˢ differs from Hbᴬ by a missense mutation substituting Valine for Glutamic Acid at position 6 of the β-chain.

• Hbᴬ / Hbˢ: No anemia; some sickling under low oxygen.

• Common in parts of Africa; one Hbˢ allele gives malaria resistance.

• This selective benefit is a heterozygous advantage.

Codominance (II)

• Genotypes & Phenotypes: Hbᴬ / Hbᴬ = normal RBCs; Hbˢ / Hbˢ = severe anemia, sickled RBCs; Hbᴬ / Hbˢ = no anemia, some slightly sickled RBCs.

• Cause: Sickle Cell Anemia — point mutation in hemoglobin (Hbˢ vs Hbᴬ).

• Dominance: Organism level — Hbᴬ is dominant; cellular level — incomplete dominance (some sickled cells).

• Protein level: Both Hbᴬ and Hbˢ produced equally → codominance.

Dominant Negative Effect

• The gene product from the mutant allele interferes with the gene product from the wild type allele (see also Muller’s morph “Antimorph”), blocking the wild type function.

Gain-of-Function Effect

• The mutant allele acquires a new property not present in the wild type allele, and this new property causes a phenotype (see also Muller’s morph “Hypermorph” and “Neomorph”).

Dominance of a Mutant Allele Ex. 1

• When a mutant protein interacts with the normal protein it can render the protein as non-functional.

  • The shape is altered. 

• Mutant affects the function by b/e non-functional or reduce its function. 

• This can be dimer, tetrameter, etc. 

Dominance of a Mutant Allele Ex. 2

• The normal protein is affected by binding to the mutated protein.

• As a result, the dimer is non-functional.

Mutant Allele Classification

• Dominance/recessive describes relationships between alleles, not individual alleles themselves.

• A more useful system classifies alleles based on the type of genetic defect.

• H.J. Muller (Nobel Prize, 1946) designated five classes of mutant alleles called “morphs” (meaning “form”).

• These classifications are still used today, sometimes alongside modern equivalents.

Amorph (Null) Mutations

• “A” = absence; complete loss-of-function; also called null mutation.

• Caused by deletions, missense mutations that inactivate protein, or nonsense mutations.

• Classification is based on phenotype, not the type of molecular change.

• Any mutation causing total loss-of-function is an amorphic allele.

Hypomorphs

• “Hypo” = reduced; allele is partially functional but below wild-type levels.

• Most commonly used term in Muller’s system; modern equivalents: partial loss-of-function or leaky.

• Mutation may affect a regulatory element (reducing gene expression).

• Or a point mutation may reduce the activity of the gene product.

Hypomorphs

• Mutation in the regulatory region. 

• mRNA stability, doesn’t interact as good with a protein partner, etc. 

• All can lead to hypomorphism.

Porphyrias

• Porphyrias affect heme biosynthesis (8 genes).

• Most disease-causing alleles are amorphic or hypomorphic; patients usually heterozygous or heteroallelic.

• Heme precursors build up in the mitochondria.

• Complete loss of heme is lethal.

Porphyrias - Symptoms & Treatment

• Light sensitivity, gum recession, extreme neuropathic pain.

  • Sensitivity in UV.

• Heme or glucose injections can reduce symptoms.

Hypermorph (Increased Function)

• “Hyper” = increased; gene is more active than wild type.

• Modern equivalent: gain-of-function (but distinct from neomorphs).

• Cause: regulatory mutations increasing expression or coding mutations making protein more active; normal product, just more or more active.

• Gene product is produced in normal cellular context (unlike neomorphs).

Antimorphs

• “Anti” = against; mutant gene product antagonizes wild-type function (in a heterozygous setting).

• May dimerize with wild-type protein and inactivate it.

• Can also compete for substrate or binding partner.

• Usually dominant in inheritance.

Myostatin Mutations

• Function: Myostatin represses muscle growth; loss-of-function increases muscle mass.

• Cattle: Stop mutation → amorph (no myostatin).

• Sheep: Point mutation in non-coding mRNA creates microRNA binding site → hypomorph.

• Outcome: Reduced myostatin activity increases muscle; mutation type determines amorph vs hypomorph.

Neomorphs

• “Neo” as in “new.”

• The mutant gene product acquires a new function not found in the wild type protein.

• This could involve new interactions, new substrates, or expression in the wrong cell type or developmental stage.

• Are generally dominant or semidominant.

Oncogenes - Relocation

• Example: Burkitt lymphoma caused by relocation of MYC oncogene next to a new regulatory element.

• MYC: normally important for cell proliferation.

• Mechanism: Recombination with chromosome 14 places MYC under incorrect regulatory control.

• Result: gain of new function leading to abnormal cell proliferation (neomorph).

Oncogenes - Hybrid

• Disease: Chronic Myelogenous Leukemia (CML).

• Mechanism: Translocation between chromosome 9 (ABL) and chromosome 22 (BCR1).

• Result: Formation of BCR-ABL fusion gene → hybrid oncogene.

Proto-Oncogene

• The wild-type version of the oncogene.

Mutation Classification

• Classification schemes are not mutually exclusive; they describe mutations at different levels:

  • DNA/chemical level: e.g., frameshift.

  • Gene product level: e.g., functional vs nonfunctional.

  • Phenotypic level: mutant vs wild type.

Allelic Interactions

• Dominant vs recessive, incomplete (semi-) dominance, codominance.

• Patterns depend on perspective, e.g., cell vs organism.

Muller’s Morphs

• Classify all types of mutations.

  • Amorph, hypomorph, hypermorph, neomorph, and antimorph. 

Complementation Tests

• Used to determine if mutations are in the same or different genes.

• Mutations that complement: occur in different genes → non-allelic mutations.

• Mutations that fail to complement: occur in the same gene → allelic mutations.

Complementation in Genetic Screens

• Complementation tests help identify new mutants.

• After a genetic screen, we may have multiple mutants but don’t know if the same gene is affected more than once.

• Complementation allows us to group mutants by gene.

• Understanding this requires knowing how genetic screens are conducted.

Chemical Mutagenesis (Classic Approach)

• Method: Feed a chemical mutagen, usually to males, to mutagenize sperm.

• Efficiency: More efficient than X-rays; one male can fertilize many females.

• Common mutagen: EMS (ethylmethane sulfonate).

• Effect: Mostly G→A and T→C transitions; used in Drosophila, C. elegans, Arabidopsis.

EMS-Induced Mutations

• EMS (ethylmethane sulfonate, C₃H₈SO₃) is an alkylating agent that adds ethyl groups to nucleotides.

• Causes mispairing during DNA replication → point mutations.

• Commonly used in genetic screens.

• Efficient for creating G→A and T→C transitions.

Mutant Hunts = Genetic Screens

• Animals are mutagenized and thousands of progeny are examined to isolate new mutants.

• Heidelberg Screen (1979–1980, Drosophila): analyzed abnormal larval cuticle patterns.

• Isolated 600 mutants representing 120 genes using complementation tests.

• One of the most famous mutant hunts in developmental biology.

Heidelberg Screen Impact

• Revolutionized understanding of developmental processes.

• Many genes discovered are conserved in humans.

• Genes serve as models for human diseases.

• Nobel Prize 1995 awarded to Eric Wieschaus & Christiane Nüsslein-Volhard.

Preaxial Polydactyly

• Can be caused by mutation in the regulatory region of the human sonic hedgehog gene, which is important for limb development.