Chromosome Theory of Inheritance

Introduction

The chromosome theory of inheritance states that genes are located on chromosomes, and the behavior of chromosomes during meiosis accounts for inheritance patterns. Early experiments by Thomas Hunt Morgan using Drosophila melanogaster (fruit flies) provided strong evidence for this theory.

Fruit Flies as Model Organisms

• High Reproductive Rate: Fruit flies produce many offspring, allowing for statistical analysis of inheritance.

• Short Generation Time: A new generation can be bred every two weeks.

• Simple Chromosome Number: Only four pairs of chromosomes, making genetic studies manageable.

Wild Type vs. Mutant Phenotypes

Morgan distinguished between wild type (normal) phenotypes and mutant phenotypes in fruit flies. Wild type traits are common in the population, while mutant traits are alternatives.

• Wild type: Red eyes

• Mutant: White eyes

Correlating Gene and Chromosome Behavior

Morgan's experiments showed that the white-eyed mutant allele is located on the X chromosome. Female flies (XX) and male flies (XY) display different inheritance patterns, supporting the chromosome theory.

Sex-Linked Inheritance

Sex Chromosomes and Sex Determination

• X and Y Chromosomes: Mammals have a larger X and a smaller Y chromosome.

• SRY Gene: Located on the Y chromosome, responsible for testis development.

• Sex-Linked Genes: Genes located on either sex chromosome; X-linked genes are more numerous and can affect traits unrelated to sex.

Patterns of Inheritance

• Recessive X-Linked Traits: Females require two copies of the allele; males require only one.

• Hemizygosity: Males are hemizygous for X-linked genes, making recessive disorders more common in males.

X Inactivation and Barr Bodies

In female mammals, one X chromosome is randomly inactivated during embryonic development, forming a Barr body. This leads to mosaicism for X-linked traits.

• XIST Gene: Responsible for X inactivation.

• Mosaicism: Heterozygous females may display two phenotypes, such as different fur colors in cats.

Linked Genes and Genetic Mapping

Linked Genes

Genes located near each other on the same chromosome tend to be inherited together. Parental phenotypes are more common, while recombinants arise from crossing over.

Recombination and Genetic Maps

• Recombination Frequency: The percentage of recombinant offspring indicates the distance between genes.

• Linkage Map: An ordered list of genetic loci based on recombination frequencies.

• Map Unit: One map unit equals a 1% recombination frequency.

Formula: Recombination frequency (%) = (Number of recombinant offspring / Total offspring) × 100

Alterations in Chromosome Number and Structure

Abnormal Chromosome Number

Nondisjunction during meiosis can result in gametes with abnormal chromosome numbers, leading to conditions such as aneuploidy and polyploidy.

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

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

Human Disorders Due to Chromosomal Alterations

• Down Syndrome (Trisomy 21): Caused by three copies of chromosome 21.

• Klinefelter Syndrome: XXY males.

• Turner Syndrome: X0 females.

Alterations of Chromosome Structure

• Deletion: Removal of a chromosomal fragment.

• Duplication: Repetition of a segment.

• Inversion: Reversal of a segment's orientation.

• Translocation: Movement of a segment to another chromosome.

Exceptions to Mendelian Genetics

Genomic Imprinting

Genomic imprinting involves the silencing of certain genes depending on which parent passes them on. Most imprinted genes are on autosomes and are regulated by methylation of DNA.

• Imprinting: The phenotype depends on the parent of origin.

• Methylation: Addition of —CH3 groups to DNA, silencing gene expression.

Inheritance of Organelle Genes

Extranuclear genes are found in mitochondria and chloroplasts. These genes are inherited maternally, as the zygote's cytoplasm comes from the egg. Defects in mitochondrial genes can cause diseases affecting energy production.

• Mitochondrial Myopathy: Disease caused by defective mitochondrial genes.

• Leber’s Hereditary Optic Neuropathy: Another example of mitochondrial inheritance.

Summary Table: Types of Chromosomal Alterations

Additional info: Polyploidy is more common in plants and can lead to speciation, while aneuploidy often results in developmental disorders in animals.