Genetics and Inheritance Notes

Mendel's Ideas

  • Parents pass on traits to their kids.
  • True breeding means homozygous.

True Breeding

  • True breeding = homozygous.
  • Scenario: test cross with a true breeding parent.
  • Two true breeding parents: homozygous dominant x homozygous recessive.
  • Hybrid: heterozygous.
  • Dihybrid: two traits, but still true breeding = all homozygous.
  • Even with three traits, true breeding means all are homozygous.

Generations

  • P, F1, F2, F3, F4.
  • P: parent generation.
  • F1: first generation offspring.
  • F2: second generation offspring.

Punnett Squares

  • Show probability of offspring, not quantities.
  • Example: two true breeding parents, one purple, one white.
    • All offspring are purple, thus purple is likely dominant and white is recessive.
    • Punnett square yields all heterozygous offspring.
  • F2 generation created by crossing F1 with F1.
    • Cross heterozygotes to make F2.
    • 3:1 phenotypic ratio.

Mendel's Rules

  • Alternative versions of a gene are called alleles.
  • Allele: a singular letter (e.g., big A).
  • Alternative version is still an allele (e.g., little a).
  • We inherit alleles from our parents.
  • Mendel: some alleles are dominant, some are recessive.
  • Homologous chromosomes have alleles for a gene at a specific location called the locus.

Law of Segregation

  • Related to meiosis.
  • Original germline cell duplicates DNA during S phase.
  • Meiosis I and Meiosis II result in four gametes.
  • Each gamete has only one allele for each trait.
  • Example: 1A, 1B, 1C, 1D in each gamete, despite 23,000 traits in humans.
  • Egg has one gamete, sperm has the other; they combine during fertilization.

Genotypes and Phenotypes

  • Homozygous dominant, homozygous recessive, heterozygous.
  • No such thing as heterozygous dominant.
  • Phenotype: what you see.
  • Genotype: genetic makeup (e.g., AaAa).
  • Use good letters (avoid 'p') when setting up Punnett squares.

Test Cross

  • Cross an unknown genotype with a known genotype.
  • Known is typically homozygous recessive (e.g., aaaa).
  • Example: purple flower (unknown) crossed with white flower (known aaaa).
  • If 100% offspring have dominant trait, unknown was homozygous dominant.
  • If 50/50 dominant/recessive phenotype, unknown was heterozygous.

Independent Assortment

  • Relates to meiosis.
  • Tetrads align independently.
  • Applies when more than one trait is involved.
  • Trait A is independent of Trait B if they're on separate tetrads.
  • Must be able to determine possible gametes from a genotype.
  • Example: AABBAABB parent can only produce ABAB gametes.
  • Example: AaBbAaBb parent can produce ABAB, AbAb, aBaB, abab gametes.

Dihybrid Cross

  • Cross two parents that are true breeding for two traits.
  • Cross gametes, resulting in all heterozygous offspring.
  • Cross these offspring to see the F2 generation.
  • Phenotypic ratio: 9:3:3:1.
Phenotypic Ratio Breakdown
  • 9: dominant dominant.
  • 3: dominant recessive.
  • 3: recessive dominant.
  • 1: recessive recessive.
  • Helpful for chi-squared questions.
Linked Genes
  • If the ratio is not 9:3:3:1, suspect gene linkage.
  • Genes are on the same tetrad.

Multiplication Rule

  • Probability of multiple events happening.
  • Multiply each event's probability.
  • Example: chance of three daughters in a row is 12⋅12⋅12=18\frac{1}{2} \cdot \frac{1}{2} \cdot \frac{1}{2} = \frac{1}{8}.
  • Chance of a fourth child being a girl is still 12\frac{1}{2} (singular event).
  • Use probability to calculate the chances of offspring genotypes, instead of large Punnett squares.
    • e.g., cross YyRrYyRr with YyRrYyRr. Find probability of homozygous dominant YYRRYYRR offspring.
    • Probability of YYYY is 14\frac{1}{4}, probability of RRRR is 14\frac{1}{4}.
    • Probability of YYRRYYRR is 14⋅14=116\frac{1}{4} \cdot \frac{1}{4} = \frac{1}{16}.

Dominance

Complete Dominance
  • One allele is completely dominant over the other.
  • Status quo; normal.
  • Indicated by uppercase and lowercase letters.
Codominance
  • Both alleles are fully dominant.
  • Example: blood type A, B.
  • Splotchy coloration in animals/plants (e.g., white and brown, white and pink).
Blood Type Genotypes
  • Type A: IAIAI^AI^A or IAiI^Ai.
  • Type B: IBIBI^BI^B or IBiI^Bi.
  • Type AB: IAIBI^AI^B (codominance).
  • Type O: iiii (both alleles recessive).
Incomplete Dominance
  • Blending of traits.
  • Example: Snapdragon flowers.
    • Red (CRCRCRCR) x White (CWCWCWCW) = Pink (CRCWCRCW).
    • Pink x Pink yields red, pink, or white flowers.
  • Hallmark: three phenotypes observed from crossing heterozygotes (1:2:1 ratio).
Other Considerations
  • Dominant allele is not always most common.
  • Pleiotropy: one gene affects multiple phenotypic effects.
  • Epistasis: one gene overrides another.
    • Example: mouse coloration where gene C overrides gene B.
    • Recessive cccc means no pigment, regardless of gene B.
  • Polygenetic inheritance: more than one gene codes for a single phenotype.
    • Example: skin color (three genes, six alleles).
    • Cumulative sum of dominant/recessive alleles determines phenotype.

Pedigrees

  • Expect multiple questions; read backgrounds carefully.
  • Hypothesize inheritance pattern (X-linked dominant/recessive, autosomal dominant/recessive, mitochondrial).
  • Filled-in = recessive (hypothesis); non-filled = dominant.
  • Test the hypothesis with Punnett squares.
  • If a trait skips a generation, start with the hypothesis that it's recessive.
Recessively Inherited Disorders
  • Heterozygotes are carriers; do not have the disorder.
Dominantly Inherited Disorders
  • No carrier status; you either have it or you don't.
Multifactorial Disease
  • Not always relevant.

Chromosomal Theory of Inheritance

  • Traits are on chromosomes.
  • If traits are on separate tetrads, they are independent and follow the law of independent assortment (9:3:3:1 ratio).
  • If traits are on the same chromosome, they are linked and inherited together (sometimes; crossing over can separate them).
Thomas Hunt Morgan's Experiment
  • Fruit flies.
  • Eye color is usually coded on the X chromosome.
Wild Type
  • Most common phenotype; annotated with a superscript plus (^+$).
  • Does not necessarily mean dominant.
  • Example: female with red eyes (X^{+}X^{+}$, wild type) crossed with male with white eyes (XY).

Linked Genes

  • Genes on the same chromosome.
  • Can deviate from expected ratios.
  • Testcross: heterozygote crossed with homozygous mutant (recessive).
  • Example: Gray normal (GgNn)xHomozygousmutant() x Homozygous mutant (ggnn
  • Four phenotypes may be observed, but the ratios are not equal (1:1:1:1).
  • More parental types and fewer recombinants typically indicates linked genes.
  • Chi-squared test can determine if observed ratios differ significantly from expected.
  • Calculate expected values assuming independent assortment (e.g., \frac{1}{4}$$ of total offspring).

Recombination Frequency

  • (# of recombinants / total # of offspring) x 100%.
  • Indicates the distance between genes (map units).
  • The higher the recombination frequency, the further apart the genes are.
  • Recombination frequency of 50% means genes are either far apart on the same chromosome or on separate chromosomes.

Map Units

  • Measure distance between genes.
  • 1 map unit = 1% recombination frequency.
  • Example: If genes A and B are 15 map units apart, there is a 15% chance of recombination.
  • For genes more than 50 map units apart, recombination frequency is considered 50%.

Sex-Linked Genes

  • Females are XX, males are XY.
  • Read backgrounds carefully for questions about other sex determination systems.

X-Linked Recessive Disorders

  • Males more likely to be affected than females.
  • Females can be carriers without having the disorder.
  • Males cannot be carriers; they either have it or they don't.

Barr Bodies

  • In females, one X chromosome is randomly inactivated and becomes a Barr body.
  • Inactivation occurs through methylation.
Cat Coloration Example
  • Calico cats or tortoise shell cats are female (XX).
  • One X chromosome has a gene for black fur, the other for orange fur.

Nondisjunction

  • Chromosomes don't separate properly during meiosis.
  • Leads to Aneuploidy: wrong chromosome number in gametes.
  • Trisomy: one too many chromosomes.
  • Monosomy: one too few chromosomes.
  • If nondisjunction occurs in meiosis I, all gametes are affected (either n+1 or n-1).
  • If nondisjunction occurs in meiosis II, two gametes are normal, and two are affected (one n+1 and one n-1).
  • Lack of crossover can be a cause of nondisjunction.

Polyploidy

  • More than two sets of chromosomes.
  • Diploid: two of each chromosome.
  • Polyploid: more than two of each chromosome (e.g., four of each = tetraploid).

Chromosomal Mutations

  • Deletion: loss of a chromosome segment.
  • Duplication: repetition of a chromosome segment.
  • Inversion: reversal of a chromosome segment.
  • Translocation: movement of a chromosome segment to a nonhomologous chromosome.

Karyotypes

  • Check chromosome 21 first for trisomy (Down syndrome).
  • Check sex chromosomes (Klinefelter syndrome: XXY, Turner syndrome: X).
  • XXY male has one Barr body. X female has no Barr bodies.

Genomic Imprinting

  • Expression of an allele depends on whether it is inherited from the mother or father.
  • Mendelian inheritance doesn't apply.
  • Read for unique situations.

Mitochondrial Inheritance

  • Mitochondria are inherited from the mother.
  • If the mother has a mitochondrial disorder, all her children will have it.
  • The father does not pass on mitochondrial conditions.

Viruses

  • Structure: genetic material (DNA or RNA), capsid (protein coat), envelope (membrane, not always present).
  • Goal is to get inside a cell, hijack the cell, and build more virus particles.
  • Non-living; no ribosomes or metabolism.
Bacteriophage Reproduction
  • Lytic Cycle: quick, rapid death of host cell (24-48 hours).
  • Lysogenic Cycle: viral DNA is incorporated into host DNA, host multiplies with viral DNA inside then a trigger will cause it to go into the Lytic cycle.
Retroviruses
  • Have reverse transcriptase, which converts RNA to DNA.
  • HIV is a retrovirus.

Reverse Transcription

  • Breaks the rules of the central dogma going from RNA to DNA.

Viral Transmission

  • Horizontal transmission: from plant to plant.
  • Vertical transmission: from infected parent to seeds/offspring.
  • Viroids: pieces of RNA that infect plants.
  • Prions: infectious proteins.

DNA Packaging

  • DNA is wound around nucleosomes (made of histones).
  • Nucleosomes are condensed into 30-nanometer fiber.
  • Fiber is further compacted and folded into chromosome shape.
  • Histones can be acetylated and DNA can be methylated.

Chromatin

Heterochromatin
  • More Condenses (centromere, telomere).
  • Has been Methylated.
Euchromatin
  • True chromatin.
  • Acetylation, more accessible, more genes expressed.

Transposons

  • Copy and paste.
  • Pieces of DNA that can copy themselves and insert themselves elsewhere.
  • Retrotransposons use reverse transcriptase.

Epigenetics

  • Inheritance of methylation and acetylation event to offspring.

Proteosomes

  • Digest proteins.

Oncogenes and Proto-Oncogenes

  • Oncogenes contribute to cancer.
  • Proto-oncogenes are what you are born with.
  • Examples: RAS and p53 pathways.