Notes on The Chromosomal Basis of Inheritance

Overview: The Chromosomal Basis of Inheritance

• Mendel's "hereditary factors" are now identified as genes.
• Genes are located on chromosomes, observable by tagging chromosomes with fluorescent dye.

Mitosis and Meiosis

• Mitosis and meiosis were first described in the late 1800s.
• The chromosome theory of inheritance states that Mendelian genes are found at specific loci on chromosomes.
• Chromosomes undergo segregation and independent assortment during reproduction.
• The behavior of chromosomes during meiosis explains Mendel's laws of segregation and independent assortment.

Law of Segregation and Independent Assortment

• Law of Segregation: The two alleles for each gene separate during gamete formation.
• Law of Independent Assortment: Genes on nonhomologous chromosomes assort independently of one another.
• Gametes recombine during fertilization to produce a phenotypic ratio of 9:3:3:1 in the F2 generation.

Morgan's Contributions to Genetics

• Thomas Hunt Morgan provided the first solid evidence linking genes to specific chromosomes using the fruit fly, Drosophila melanogaster.
• Characteristics of fruit flies:
  • High offspring production.
  • Rapid generation time (about every two weeks).
  • Only four pairs of chromosomes.
• Noted the presence of wild-type and mutant phenotypes (e.g., eye color).

Eye Color Experiment

• Morgan's experiment involved crossing white-eyed male flies with red-eyed female flies:
  • F1 generation: All had red eyes.
  • F2 generation: Displayed a 3:1 ratio (red:white), with only males showing white eyes, indicating a sex-linked inheritance.
• The white-eyed mutant allele is located on the X chromosome.

Sex-Linked Inheritance

• In humans, sex is determined by X (larger) and Y (smaller) chromosomes.
• X-linked genes show specific inheritance patterns:
  • Females: XX; Males: XY.
  • A female must be homozygous (two copies) for a recessive trait to express it, whereas a male needs only one copy (hemizygous).
• Recessive X-linked disorders (e.g., color blindness, Duchenne muscular dystrophy, hemophilia) are more common in males due to their hemizygous condition.

X Inactivation in Females

• In female mammals, one X chromosome is randomly inactivated during early development, forming a Barr body.
• Heterozygous females become mosaics for expression of X-linked traits, as some cells express one allele and others express the alternate allele.

Linked Genes and Genetic Recombination

• Linked genes are located on the same chromosome and tend to be inherited together.
• Morgan's experiments with fruit flies showed linked genes affect inheritance.
• Nonparental phenotypes arise from genetic recombination via crossing over during meiosis.

Mapping Genes Using Recombination Data

• Alfred Sturtevant constructed genetic maps based on recombination frequencies.
• Genes far apart on a chromosome show higher recombination frequencies, while closely linked genes show less crossing over.
• 1 map unit corresponds to a 1% recombination frequency.

Chromosomal Alterations and Genetic Disorders

• Large-scale chromosomal alterations can lead to developmental disorders or miscarriages.
• Nondisjunction causes gametes to have abnormal numbers of chromosomes:
  • Aneuploidy: Abnormal chromosome count, such as monosomy (1 copy) or trisomy (3 copies).
  • Polyploidy: More than two sets of chromosomes, common in plants.
• Types of chromosomal structural changes:
  • Deletion: Segment is removed.
  • Duplication: Segment is repeated.
  • Inversion: Segment is reversed.
  • Translocation: Segment is moved from one chromosome to another.

Human Disorders Due to Chromosomal Alterations

• Down syndrome (Trisomy 21) is characterized by three copies of chromosome 21, with increased incidence in older mothers.
• Syndromes like Klinefelter (XXY) and Turner Syndrome (X0) are results of sex chromosome nondisjunction.
• Structural alterations can lead to syndromes like cri du chat, linked to specific deletions.