Lecture 2

Genetic Foundations

• Humans are made up of trillions of cells.
• Within every cell (except red blood cells) is a nucleus.
• The nucleus contains rod-like structures called chromosomes.

Chromosomes

• Store and transmit our genetic information.
• Humans have 23 matching pairs of chromosomes in each cell (22 autosomes + 1 pair of sex chromosomes).
• In each pair, one member is inherited from the mother and one from the father.
• The 23rd pair determines sex: XX in females; XY in males.

Deoxyribonucleic Acid (DNA)

• Chromosomes are made up of DNA.
• DNA is a long, double-stranded molecule that resembles a ladder.
• Each rung consists of a pair of chemical substances called bases.
• Base pairing is consistent: $ext{A} ext{ pairs with } ext{T}, ext{ and } ext{C} ext{ pairs with } ext{G}.$
  $ext{A} ext{-} ext{T} ext{ and } ext{C} ext{-} ext{G}$
• The sequence of base pairs along the DNA ladder provides genetic instructions for protein synthesis.

Proteins and Traits

• Proteins are the biological foundation on which our traits and characteristics are built (e.g., eye color, hair type).
• A change in a single base pair can influence human traits.
• Protein synthesis is the process by which genes build proteins, leading to observable traits.
• There are 10–20 million different ways proteins can be assembled to produce diverse traits.

Genes

• A gene is a segment of DNA along the length of a chromosome.
• The basic unit of heredity.
• In humans, genes vary in size from a few hundred DNA bases to more than $2{,}000{,}000$ bases.
• Genes send instructions for building proteins to the cytoplasm.
• Cytoplasm: the area surrounding the nucleus where proteins are assembled.
• Human characteristics arise from the synthesis of proteins; multiple proteins combine in millions of ways to produce traits.

Sex Chromosomes and Autosomes

• 22 of our chromosome pairs are autosomes (non-sex chromosomes).
• The 23rd pair are the sex chromosomes: XX (female) or XY (male).
• A new individual is created when two sex cells (gametes) combine.
• A gamete contains 1 set of chromosomes (23); the zygote formed has 46 chromosomes.

Reproduction and Early Development

• Identical (monozygotic) twins: 1 zygote separates into two individuals; same genetic makeup; about 1 in 330 births.
• Fraternal (dizygotic) twins: 2 zygotes; no more genetically alike than ordinary siblings; about 1 in 60 births in the U.S.

Patterns of Genetic Influence

• There are various patterns by which genes influence traits:
  • Dominant-recessive inheritance
  • Incomplete dominance
  • X-linked inheritance
  • Genomic imprinting
  • Mutation

Genes & Alleles

• There are two forms of each gene (two alleles) that exist on paired chromosomes.
• One form is inherited from the mother; one from the father.
• Allele: one of the forms of each gene.
• Organisms have 2 alleles for each trait.

Heterozygous vs. Homozygous Gene Pair

• Heterozygous: 1 dominant allele and 1 recessive allele (Aa).
  • Dominant allele is expressed; recessive is masked.
• Homozygous: both alleles are the same (AA or aa).
  • Trait is expressed accordingly.

Punnett Square Example: Eye Color

• If both parents are heterozygous carriers (Bb) for the recessive blue-eye trait (b):
  • 25% of offspring are BB, 50% are Bb, 25% are bb.
• Expressed as probabilities: $P(BB)=0.25,\, P(Bb)=0.5,\, P(bb)=0.25.$

Genotype vs. Phenotype

• Genotype: the set of genes that an organism carries.
• Phenotype: all observable characteristics, influenced by genotype and environment.

Patterns: Dominant-Recessive Inheritance (Cont’d)

• Many disabilities and diseases are the product of recessive alleles.
• Phenylketonuria (PKU): a recessive disorder where infants lack the enzyme to break down phenylalanine, which can cause CNS damage.
  • Newborn screening is required in the U.S.; early treatment is available when detected.
• Cross example: If both parents are heterozygous carriers of a recessive gene (p):
  • 25% normal (NN), 50% carriers (Np), 25% affected (pp).
  • Diagrammatic cross:
  • N from Mom and N from Dad → NN; N from Mom and p from Dad → Np; p from Mom and N from Dad → Np; p from Mom and p from Dad → pp.

Patterns: Incomplete Dominance

• In some heterozygous cases, the dominant-recessive relationship does not hold.
• Incomplete dominance: both alleles are expressed in the phenotype, producing a trait that is intermediate between the two.

Example: Sickle Cell Anemia

• Sickle cell disease results from a mutation in the hemoglobin gene.
• Heterozygous individuals (carriers) are typically protected from malaria but may experience issues under oxygen deprivation.
• If oxygen deprivation occurs, a mild or temporary form of illness can appear.
• Resources: quick explanations and personal accounts exist (e.g., Life With Sickle Cell).

Patterns: X-Linked Inheritance

• Describes inheritance when a harmful allele is carried on the X chromosome.
• Females: recessive alleles on one X can be suppressed by a dominant allele on the other X.
• Males: have only one X and one Y, so there is no second X to override a recessive allele.
• Therefore, males are more likely to be affected.
• Predictive outcomes: 50% of male children may be affected; 50% of female children may be carriers under certain conditions.

Patterns: Genomic Imprinting & Mutation

• Imprinting: Alleles are chemically marked (imprinted) to activate either the father’s or mother’s gene; often temporary.
• Mutation: A sudden, permanent change in a DNA segment; may affect a single gene or involve many genes (chromosomal disorders); caused by chance or environmental hazards.

Chromosomal Abnormalities

• Chromosomal abnormalities occur when part of a chromosome is missing, extra, swapped to another chromosome, or inverted.
• Down syndrome: caused by an extra copy of chromosome 21; features include growth delays, mild-to-moderate intellectual disability, and characteristic facial features.
  • Incidence: $\frac{1}{700}$ births.
  • In about $95\%$ of cases, a gamete has an extra copy of chromosome 21, leading to a zygote with 47 chromosomes (instead of 46).
• Abnormalities: Sex Chromosomal Disorders (examples below) impact development and function:
  • XYY syndrome: extra Y chromosome; taller stature, large teeth; generally normal intelligence and development; incidence $\approx 1/1000$ male births.
  • Triple X syndrome (XXX): extra X chromosome in females; tallness, verbal difficulties; incidence $\approx 1/500\text{-}1{,}250$ female births.
  • Klinefelter syndrome (XXY): extra X chromosome in males; tall stature, incomplete puberty; incidence $\approx 1/900$ male births; treatment includes hormone therapy and special education.
  • Turner syndrome (XO): missing X chromosome in females; short stature, webbed neck, incomplete puberty; incidence $\approx 1/2500\text{-}8{,}000$ female births; treatment includes growth hormone and educational support.

Reproductive Choices and Counseling

• Reproductive options include Genetic Counseling, Prenatal Diagnosis and Fetal Medicine, and Adoption.

Genetic Counseling

• TEDxHelena video: Jaclyn Hevena — What is Genetic Counseling? (8-min).
• Purpose: A communication process designed to help couples assess their chances of having a baby with a hereditary disorder and choose the best course of action given risks and family goals.
• In many disorders, blood tests or genetic analyses can reveal whether a parent is a carrier for the harmful gene.
• What is a Genetic Counselor? (4-min) Discussion questions: Is it better to know or not to know?

Prenatal Diagnosis and Fetal Medicine

• For couples who may have a child with abnormalities, several prenatal diagnostic methods are available.
• Refer to Table 2.5 (pg. 64) for a summary of methods.
• Fetal medicine and fetal surgery exist to repair certain defects.

The Adoption Option

• Adoption is presented as an alternative reproductive choice when genetic risks are high or when prenatal diagnoses indicate significant concerns.

Connections and Implications

• Ethical, philosophical, and practical implications include questions about genetic knowledge, parental decision-making, and access to counseling and prenatal care.
• Real-world relevance includes newborn screening programs (e.g., PKU testing) and decisions about potential interventions.