Chromosomal Basis of Inheritance

Introduction

This chapter explores how chromosomes carry genetic information and how their behavior during meiosis underlies Mendelian inheritance patterns. It also examines the consequences of chromosomal alterations and the inheritance of sex-linked traits.

Key Concepts from Mendelian Genetics

Principles of Inheritance

• Law of Dominance: In a heterozygote, one allele may mask the expression of another (dominant vs. recessive alleles).

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

• Law of Independent Assortment: Genes for different traits can segregate independently during the formation of gametes, provided they are on different chromosomes or far apart on the same chromosome.

Example: Dihybrid crosses (e.g., yellow round seeds x green wrinkled seeds in peas) demonstrate independent assortment, resulting in a 9:3:3:1 phenotypic ratio in the F2 generation.

Sex-Linked Inheritance

X-Linked and Y-Linked Genes

• Sex Chromosomes: In humans, females are XX and males are XY. Genes located on these chromosomes are called sex-linked genes.

• X-Linked Genes: Genes found on the X chromosome. Males (XY) are more likely to express X-linked recessive disorders because they have only one X chromosome.

• Y-Linked Genes: Genes found on the Y chromosome. These are passed from father to son and affect only males.

Example: Hemophilia in the descendants of Queen Victoria is a classic case of X-linked recessive inheritance. Males are more frequently affected, while females can be carriers.

Pedigree Analysis

• Pedigrees are used to track inheritance patterns of traits through generations.

• Symbols: Squares represent males, circles represent females. Shaded symbols indicate affected individuals; half-shaded indicate carriers.

X Chromosome Inactivation

• In XX females, one X chromosome is randomly inactivated in each cell, forming a Barr body.

• This process ensures dosage compensation between males and females.

• Example: Calico cats display mosaic fur color due to X inactivation.

Thomas Hunt Morgan and Drosophila Genetics

Model Organism: Drosophila melanogaster

• Fruit flies are used to study inheritance due to their short generation time and easily observable traits.

• Morgan's experiments with eye color demonstrated sex-linked inheritance.

Example: Crossing red-eyed (wild type) and white-eyed (mutant) flies showed that the white-eye trait is X-linked and recessive.

Linked Genes and Genetic Mapping

Linked Genes

• Genes located close together on the same chromosome tend to be inherited together (linked genes).

• Crossing over during meiosis can separate linked genes, producing recombinant offspring.

Recombination Frequency and Map Units

• Recombination Frequency: The percentage of recombinant offspring is used to estimate the distance between genes.

• Map Unit (centimorgan, cM): 1 map unit = 1% recombination frequency.

Formula:

Example: If 94 out of 1,566 offspring are recombinants, the recombination frequency is , or 6 map units.

Chromosomal Alterations and Human Disease

Aneuploidy

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

• Nondisjunction: Failure of chromosomes to separate properly during meiosis, leading to gametes with extra or missing chromosomes.

Examples:

• Down Syndrome (Trisomy 21)

• Klinefelter Syndrome (XXY)

Structural Chromosomal Alterations

Key Terms

• Wild type: The most common phenotype in a population.

• Autosome: Any chromosome that is not a sex chromosome.

• Sex chromosome: Chromosomes involved in determining sex (X and Y in humans).

• Parental type offspring: Offspring with phenotypes matching one of the parents.

• Recombinant offspring: Offspring with new combinations of traits not found in either parent.

• Monosomic: Having one less chromosome than normal (2n-1).

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

• Nondisjunction: Failure of chromosomes to separate during meiosis.

• Translocation: Movement of a chromosome segment to a different chromosome.