Unit 2 Genetics: DNA, Genes, Inheritance, and Pedigrees

Morning objectives and study guidance

• Morning objectives: each chapter starts with clear goals for what you should be able to do with the material.
• When you get exams back: compare your work to the unit 1 learning objectives to guide study for subsequent topics.
• Use the objectives as a guideline to study and build on previously learned material.

DNA, genes, alleles, and basic inheritance concepts

• DNA is a large molecule with a long sequence of nucleotides: adenine (A), cytosine (C), thymine (T), and guanine (G).

• Reading the genetic sequence along the DNA strand yields the genetic code.

• Within the DNA sequence, regions code for products; these regions are called genes.

• A gene is a section of DNA that codes for a specific protein or RNA molecule (typically proteins in this course).

• Genes drive traits in the body; some traits are obvious and visible (e.g., eye color).

• Variants of a gene are alleles; different alleles can code for different versions of a trait.

• Example: eye color gene on chromosome 8, with different alleles potentially producing brown, blue, or green eyes.

• Genetic variation can lead to traits like cilantro tasting like soap for some individuals due to a different allele.

• Homologous chromosomes and karyotypes:

  • Homologous chromosomes are pairs that are the same size and carry the same kinds of genes.
  • A karyotype is the arrangement of chromosomes after they’re separated by size/shape/content.
  • Humans have 22 pairs of autosomes plus the sex chromosome pair (23rd): XX in females, XY in males (usually).
  • Note: homologous does not mean identical; they carry the same genes, but may carry different alleles.

• Alleles and gene versions:

  • Each chromosome in a homologous pair carries a gene; the versions on each chromosome are alleles.
  • Different versions of the same gene are called alleles (e.g., eye color alleles).
  • A gene may have different versions (alleles) on the homologous chromosomes, producing different phenotypes.

• Genotype vs phenotype:

  • Genotype: the exact allelic composition for a gene (e.g., "ff", "Ff", "FF").
  • Phenotype: the observable trait resulting from the genotype (e.g., freckles present or not).
  • Three possible genotypes for a single gene with two alleles: little f (f), big F (F) on each chromosome lead to combinations: $ff$, $Ff$, $FF$.
  • Heterozygous genotype (two different alleles) is written as $Ff$; homozygous as $FF$ or $ff$.

• Dominant and recessive alleles:

  • The dominant allele is the version that determines the phenotype when present in at least one copy in a heterozygote.
  • The recessive allele only determines the phenotype when two copies are present (homozygous recessive).
  • Example: freckles as the dominant trait; the dominant phenotype appears in heterozygotes or homozygous dominants.
  • In a heterozygote, the dominant trait is expressed even though a recessive allele is also present.

• Terminology recap:

  • Homozygous dominant: two copies of the dominant allele (e.g., FF).
  • Homozygous recessive: two copies of the recessive allele (e.g., ff).
  • Heterozygous: one dominant and one recessive allele (e.g., Ff).
  • Dominant phenotype: the trait that is expressed in the presence of at least one dominant allele.
  • Recessive phenotype: the trait expressed only when two recessive alleles are present.

Modes of inheritance and basic tools to predict outcomes

• Predicting inheritance across generations is aided by crosses and tools like Punnett squares.

• Meiosis recap (link to unit 1): DNA duplicates, chromosomes align, homologs separate in meiosis I, sister chromatids separate in meiosis II, producing gametes with one chromosome per gene.

• Fertilization: random union of a sperm and egg determines offspring genotype.

• Punnett square (monohybrid cross): one gene, two alleles

  • Example setup: one parent with $ff$ (homozygous recessive) on the top; the other with $FF$ (homozygous dominant) on the side.
  • Split alleles and fill the grid to find offspring genotypes.
  • Case outcome: all offspring are $Ff$ (heterozygous).
  • If crossing two homozygous individuals with different traits (FF × ff): all offspring are $Ff$ (100% heterozygous).
  • When crossing two heterozygotes ($Ff imes Ff$): genotypic ratio is $1:2:1$ for $FF:Ff:ff$; phenotypic ratio is $3:1$ (dominant:recessive).
  • Genotype ratio: ext{FF}: ext{Ff}: ext{ff} = 1:2:1
  • Phenotype ratio: ext{dominant phenotype}: ext{recessive phenotype} = 3:1
  • Takeaway: heterozygotes display the dominant trait in a monohybrid cross.

• Pedigrees (tracking traits through generations)

  • Symbols: squares = males; circles = females.
  • Filled shapes = affected by the trait; open shapes = unaffected.
  • Lines indicate relationships and offspring.
  • Dominant trait in pedigrees: affected individuals typically have at least one affected parent (one copy of the dominant allele is enough to express the trait).
  • Recessive trait in pedigrees: affected individuals have two copies of the recessive allele; parents can be unaffected carriers.
  • Carriers: individuals who are heterozygous for a recessive trait (one recessive allele) but do not express the trait.

Monohybrid vs dihybrid crosses

• Monohybrid cross (one gene, two alleles): recap
  • Cross between two heterozygotes ($Ff imes Ff$) yields genotypes $FF:Ff:ff = 1:2:1$ and phenotypes $3:1$.
  • Cross between a homozygous dominant and a homozygous recessive yields all heterozygotes ($Ff$), i.e., 100% dominant phenotype if complete dominance.
• Dihybrid cross (two genes, each with two alleles): example with freckles and widow's peak
  • Genes: one gene for freckles (F for dominant, f for recessive); one gene for widow's peak (W for dominant, w for recessive).
  • With parents heterozygous for both traits: $FfWw imes FfWw$.
  • After filling a 4-by-4 (16-square) Punnett square, all possible combinations are represented.
  • Phenotypic ratio for two independently assorting traits: 9:3:3:1
  • 9: freckles and widow's peak (dominant for both)
  • 3: freckles, no widow's peak (dominant for freckles, recessive for widow's peak)
  • 3: no freckles, widow's peak (recessive for freckles, dominant for widow's peak)
  • 1: no freckles, no widow's peak (recessive for both)
  • Genotypic combinations are more diverse; the 16 cells show all possible allele pairings for two genes.
  • Note: this 9:3:3:1 ratio is the most commonly observed expectation for two traits that assort independently when both parents are heterozygous for both genes.

Independent assortment and variation

• Independent assortment means the distribution of one gene’s alleles into gametes is independent of the distribution of another gene’s alleles.
• During meiosis I, homologous chromosomes align and can separate in different combinations, producing multiple possible gametes.
• Independent assortment creates genetic diversity in offspring; crosses among heterozygotes reveal multiple genotype combinations and phenotype possibilities.

Pedigrees and inheritance patterns in real populations

• Pedigrees provide a historical, observable record of trait transmission across generations without requiring knowledge of underlying alleles.
• Dominant traits in pedigrees tend to appear in every generation if they are common and individuals with the trait typically have affected parents.
• Recessive traits may skip generations if carriers pass alleles without expressing the phenotype.
• Carriers (heterozygous for a recessive trait) do not express the trait but can pass recessive alleles to offspring.

Common genetic patterns and examples

• Complete dominance (classic dominant/recessive): one copy of the dominant allele yields the dominant phenotype; recessive phenotype appears only with two recessive alleles.
  • Examples discussed: Cystic fibrosis (autosomal recessive); Huntington's disease (autosomal dominant).
  • Cystic fibrosis: two affected copies impair a protein that keeps lung mucus moving; one working copy is usually enough to avoid symptoms (carrier state).
  • Huntington's disease: one copy of the dominant allele causes the disease; heterozygotes are affected; it is autosomal dominant.
• Incomplete dominance: heterozygotes show an intermediate phenotype between the two homozygous phenotypes.
  • Classic example: sickle cell anemia (Hb gene).
  • Genotypes: HbA HbA (normal phenotype), HbA HbS (intermediate/lozenge-shaped cells), HbS HbS (sickle cell phenotype).
  • Malaria resistance can be higher in heterozygotes due to partial sickling providing some protection.
• Codominance: both alleles express independently and distinctly in the phenotype.
  • Classic example: ABO blood groups.
  • Alleles: A and B produce different sugars on red blood cells; O provides no extra sugar.
  • Genotypes and phenotypes:
  • AA or AO: blood type A
  • BB or BO: blood type B
  • AB: blood type AB (A and B expressed together)
  • ii: blood type O
  • Heterozygotes (e.g., AB) express both phenotypes distinctly rather than a blend.
• Polygenic traits: many genes contribute to a single trait, producing a range of phenotypes.
  • Example: height, skin color, and other continuous traits.
  • In a polygenic trait, the phenotype is distributed in a bell-shaped curve; the number of dominant vs recessive alleles across several genes shifts the phenotype.

Sex-linked and sex-influenced traits

• Sex-linked traits: genes located on sex chromosomes (X or Y).
  • X-linked traits: on the X chromosome only (not on the Y).
  • Example: color blindness is more common in men because men have only one X chromosome; a single affected X leads to the trait in XY males.
  • Carriers exist in females (heterozygous for a recessive X-linked trait) but often do not express the trait due to the second X carrying a normal copy.
  • Y-linked traits: located on the Y chromosome; always passed from father to son; no carriers (only males have the Y). These traits cannot skip generations and are inherited male-to-male.
  • Example of Y-linked trait: Swire syndrome (a case where the Y chromosome’s absence of a gene that switches development to male results in female development despite possessing a Y chromosome).
• Sex-influenced traits: affected by hormones; can appear differently depending on sex and hormonal environment; genes can be on any chromosome but expression is influenced by sex hormones.
• Practical implications of sex-linked inheritance include considerations for carrier testing, disease risk assessment, and family planning.

Real-world connections and ethical considerations

• Pedigree analysis allows inference about whether a trait is dominant or recessive, carrier status, and inheritance patterns without genotyping.
• Genetic counseling can use these patterns to discuss risks in offspring and potential carrier states.
• Recognize that while Punnett squares provide probabilities, actual outcomes are probabilistic and do not guarantee a particular result in any given family.
• Ethical considerations include how this information is used (privacy, discrimination, informed consent) and how individuals interpret probabilistic genetic information in personal decisions.

Key takeaways and connections to foundational principles

• DNA carries genetic information in sequences of nucleotides; specific regions code for proteins/RNAs (genes).
• Alleles provide variation; dominance determines which phenotype appears in heterozygotes.
• Genotype vs. phenotype distinction is central to predicting inheritance patterns.
• Punnett squares and Mendelian genetics describe simple patterns (monohybrid and dihybrid) under assumptions of complete dominance and independent assortment.
• There are multiple modes of inheritance beyond simple dominance (incomplete dominance, codominance, polygenic traits).
• Sex chromosomes introduce unique inheritance patterns (X-linked, Y-linked) and sex-influenced traits.
• Real-world examples (cystic fibrosis, Huntington's disease, sickle cell anemia, blood types) illustrate the diversity of inheritance patterns and their practical implications.

Equations and key ratios to remember

• Monohybrid cross (genotype):
  • If cross is $Ff imes Ff$, genotype ratio is FF:Ff:ff = 1:2:1.
  • Phenotype ratio is ext{dominant}: ext{recessive} = 3:1.
• Monohybrid cross with a strictly dominant-inheritance example (FF × ff): all offspring are Ff (100%) with the dominant phenotype.
• Dihybrid cross (two traits: F/f and W/w) with both parents heterozygous ($FfWw imes FfWw$): phenotypic ratio is
  • 9:3:3:1 for dominant-dominant : dominant-recessive : recessive-dominant : recessive-recessive.
• Pedigree interpretation uses basic probabilities of inheritance and carrier status to assess risk across generations.