Chromosomal Basis of Inheritance and DNA: Study Guide (Chapters 12 & 13)

Chromosomal Basis of Inheritance

Law of Segregation and Law of Independent Assortment

The law of segregation and the law of independent assortment are fundamental principles of inheritance first described by Gregor Mendel. These laws explain how alleles are distributed to gametes and how different genes are inherited independently.

• Law of Segregation: Each individual has two alleles for each gene, which segregate during gamete formation so that each gamete carries only one allele for each gene.

• Law of Independent Assortment: Genes for different traits assort independently of one another during gamete formation, provided they are on different chromosomes or far apart on the same chromosome.

• Example: A dihybrid cross (e.g., AaBb x AaBb) demonstrates independent assortment, resulting in a 9:3:3:1 phenotypic ratio.

Sex-Linked Genes and Patterns of Inheritance

Some genes are located on sex chromosomes (X or Y), leading to unique inheritance patterns known as sex-linked inheritance.

• Most sex-linked genes are on the X chromosome because the X chromosome is larger and contains more genes than the Y chromosome.

• X-linked recessive disorders affect males more than females because males (XY) have only one X chromosome, so a single recessive allele will cause the disorder. Females (XX) need two copies of the recessive allele.

• Examples of X-linked disorders: Hemophilia, red-green color blindness, Duchenne muscular dystrophy.

Sex Determination Mechanisms

Sex in humans is determined by the presence or absence of the Y chromosome, but other organisms use different mechanisms.

• In humans: XX = female, XY = male. The SRY gene on the Y chromosome triggers male development.

• Other mechanisms: Some species use ZW (birds: ZZ = male, ZW = female), XO (some insects), or environmental factors (e.g., temperature-dependent sex determination in reptiles).

X-Chromosome Inactivation

In female mammals, one X chromosome in each cell is randomly inactivated to balance gene dosage between males and females. This forms a Barr body.

Linked Genes and Genetic Mapping

Linked genes are genes located close together on the same chromosome and tend to be inherited together.

• Effect on Mendelian ratios: Linked genes do not assort independently, so observed ratios deviate from Mendelian predictions.

• Crossing over: Genes that are farther apart on a chromosome are more likely to be separated by crossing over during meiosis.

• Linkage map: A genetic map based on recombination frequencies, indicating the relative positions of genes on a chromosome.

Nondisjunction and Chromosomal Abnormalities

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during meiosis, leading to abnormal chromosome numbers.

• Aneuploidy: Abnormal number of chromosomes (e.g., trisomy, monosomy).

• Polyploidy: More than two complete sets of chromosomes (common in plants).

• Monosomic: Missing one chromosome (2n-1).

• Trisomic: Having an extra chromosome (2n+1).

• Viable trisomies: Chromosome 21 (Down syndrome), sometimes 13 or 18.

• Viable monosomies: Only monosomy X (Turner syndrome) is viable in humans.

DNA: The Molecular Basis of Inheritance

Discovery of DNA as Genetic Material

• Griffith's experiment: Demonstrated transformation in bacteria, suggesting a "transforming principle" (later identified as DNA).

• Hershey and Chase: Used bacteriophages to show that DNA, not protein, is the genetic material.

Chargaff’s Rule

Chargaff’s rule states that in DNA, the amount of adenine (A) equals thymine (T), and the amount of guanine (G) equals cytosine (C):

• $A = T$

• $G = C$

This helped scientists deduce the base-pairing structure of DNA.

Contributions to DNA Structure

• Rosalind Franklin: Produced X-ray diffraction images of DNA, revealing its helical structure.

• Watson and Crick: Built the first accurate model of DNA as a double helix, using Franklin’s data and Chargaff’s rules.

Structure of DNA Nucleotides

• Nucleotide components: Phosphate group, deoxyribose sugar, nitrogenous base (A, T, G, C).

• Pyrimidines: Cytosine (C) and Thymine (T) – single ring structure.

• Purines: Adenine (A) and Guanine (G) – double ring structure.

• Covalent sugar-phosphate bonds: Form the "backbone" of DNA, providing structural stability.

• Double helix: Two antiparallel strands held together by hydrogen bonds between complementary bases (A-T, G-C).

• Antiparallel: The two DNA strands run in opposite directions (5' to 3' and 3' to 5').

DNA Replication

• Semiconservative replication: Each new DNA molecule consists of one old strand and one new strand.

• Eukaryotic DNA replication: Begins at multiple origins of replication, forming replication bubbles.

• Leading strand: Synthesized continuously in the 5' to 3' direction.

• Lagging strand: Synthesized discontinuously as Okazaki fragments, later joined by DNA ligase.

• Key enzymes: DNA helicase (unwinds DNA), DNA polymerase (synthesizes new DNA), primase (adds RNA primer), DNA ligase (joins fragments).

Multiple Origins of Replication

Eukaryotic chromosomes are large and linear, so DNA replication starts at multiple sites (origins) to ensure the entire genome is copied efficiently.

Telomeres and Aging

Telomeres are repetitive DNA sequences at chromosome ends that protect genes from erosion during replication. Shortening of telomeres is associated with cellular aging.

DNA Damage and Repair Mechanisms

• DNA damage: Can be caused by UV light, chemicals, or replication errors.

• Repair mechanisms:

  • Photorepair: Uses light energy to directly reverse UV-induced damage (e.g., thymine dimers).

  • Excision repair: Damaged DNA is cut out and replaced using the undamaged strand as a template.

• Unrepaired mutations: Can lead to genetic diseases or cancer if they affect important genes.

Table: Comparison of DNA Repair Mechanisms

Repair Mechanism	Type of Damage	Process
Photorepair	UV-induced thymine dimers	Direct reversal using photolyase and light energy
Excision Repair	Various damaged or mismatched bases	Removal of damaged section and replacement by DNA polymerase

Additional info: If a mutation is not repaired, it can be passed to daughter cells during cell division, potentially leading to inherited disorders or cancer.