Chapter 15: The Chromosomal Basis of Inheritance

Introduction

This chapter explores how chromosomes are the vehicles of genetic inheritance, connecting Mendel’s principles to the physical behavior of chromosomes during cell division. It covers the discovery of sex-linked genes, linkage, recombination, and chromosomal alterations that lead to genetic disorders.

Concept 15.1: Mendelian Inheritance and Chromosome Behavior

Historical Foundations

• Mendel’s hereditary units were theoretical until microscopy revealed chromosomes’ behavior during meiosis and mitosis.

• In the early 1900s, Sutton and Boveri noted parallels between chromosome movement and Mendelian inheritance, leading to the chromosome theory of inheritance.

Experimental Evidence: Thomas Hunt Morgan

• Thomas Hunt Morgan provided the first solid evidence linking specific genes to specific chromosomes using Drosophila melanogaster (fruit flies).

• Fruit flies are ideal for genetic studies due to their short generation time, high offspring number, and only four pairs of chromosomes.

Wild Type and Mutant Phenotypes

• Wild type: The most common phenotype in a population (e.g., red eyes in fruit flies).

• Mutant phenotype: Traits that differ from the wild type (e.g., white eyes in fruit flies).

Morgan’s Crosses and Sex Linkage

• Morgan crossed white-eyed males with red-eyed females. All F1 offspring had red eyes, but in F2, only males had white eyes, suggesting the gene for eye color is on the X chromosome.

Conclusion: Chromosome Theory of Inheritance

• Morgan’s findings supported the idea that genes are located on chromosomes, specifically that the white-eye gene is X-linked.

Concept 15.2: Sex-Linked Genes and Patterns of Inheritance

Chromosomal Basis of Sex

• Humans and many animals have two sex chromosomes: X (large) and Y (small).

• Females: XX; Males: XY.

• The SRY gene on the Y chromosome triggers male development.

Sex-Linked Genes

• Sex-linked gene: Located on either sex chromosome.

• X-linked genes: About 1,100 genes on the X chromosome; many unrelated to sex determination.

• Y-linked genes: Only about 78 genes, mostly related to male sex determination.

Inheritance Patterns of X-Linked Genes

• For a recessive X-linked trait to be expressed:

  • Females need two copies (homozygous).

  • Males need only one copy (hemizygous).

• X-linked recessive disorders are more common in males (e.g., red-green color blindness, Duchenne muscular dystrophy, hemophilia).

X Inactivation in Female Mammals

• One X chromosome in each cell is randomly inactivated during embryonic development, forming a Barr body.

• Females heterozygous for X-linked genes are mosaics (e.g., tortoiseshell and calico cats).

Concept 15.3: Linked Genes and Genetic Recombination

Linked Genes

• Linked genes: Genes located near each other on the same chromosome and tend to be inherited together.

• Morgan’s experiments with fruit flies showed that some traits do not assort independently due to linkage.

Genetic Recombination

• Genetic recombination: Production of offspring with combinations of traits differing from either parent.

• Recombination of unlinked genes occurs via independent assortment; a 50% recombination frequency is expected for genes on different chromosomes.

Crossing Over

• Linked genes can be separated by crossing over during prophase I of meiosis, resulting in recombinant chromosomes.

Genetic Mapping

• Linkage map: Ordered list of genetic loci along a chromosome, based on recombination frequencies.

• One map unit (centimorgan) = 1% recombination frequency.

• Genes far apart on the same chromosome can have recombination frequencies near 50% and behave as if unlinked.

Concept 15.4: Chromosomal Alterations and Genetic Disorders

Alterations in Chromosome Number

• Nondisjunction: Failure of homologous chromosomes or sister chromatids to separate properly during meiosis, leading to abnormal chromosome numbers in gametes.

• Aneuploidy: Abnormal number of a particular chromosome (e.g., monosomy, trisomy).

• Polyploidy: More than two complete sets of chromosomes (e.g., triploidy, tetraploidy); common in plants.

Alterations in Chromosome Structure

• Chromosome breakage can cause:

  • Deletion: Loss of a segment.

  • Duplication: Repetition of a segment.

  • Inversion: Reversal of a segment.

  • Translocation: Segment moves to a nonhomologous chromosome.

Human Disorders Due to Chromosomal Alterations

• Down syndrome (Trisomy 21): Three copies of chromosome 21; frequency increases with maternal age.

• Klinefelter syndrome (XXY): Extra X chromosome in males; sterile, some female characteristics.

• Turner syndrome (X0): Only one X chromosome in females; sterile, only known viable human monosomy.

• Cri du chat syndrome: Deletion on chromosome 5; severe intellectual disability, catlike cry.

• Chronic myelogenous leukemia (CML): Caused by chromosomal translocation.

Concept 15.5: Exceptions to Standard Mendelian Inheritance

Genomic Imprinting

• Genomic imprinting: Phenotype depends on which parent passed along the allele; involves methylation and silencing of certain genes.

• Most imprinted genes are critical for embryonic development.

• Example: Only the paternal allele of the Igf2 gene is expressed in mice.

Inheritance of Organelle Genes

• Extranuclear genes (cytoplasmic genes) are found in mitochondria and chloroplasts.

• Inherited maternally because the zygote’s cytoplasm comes from the egg.

• Defects in mitochondrial genes can cause diseases affecting muscles and nerves (e.g., mitochondrial myopathy, Leber’s hereditary optic neuropathy).