Chromosomal Basis of Inheritance and Sex Determination

Chromosomes and Inheritance

Historical Foundations of Chromosomal Inheritance

The concept of genes as hereditary factors was first proposed by Mendel, but their physical basis was not understood until later. Thomas Hunt Morgan's work with Drosophila melanogaster (fruit flies) demonstrated that genes are located at specific positions (loci) on chromosomes, providing a physical explanation for Mendel's laws of inheritance.

• Gene: A unit of heredity located on a chromosome.

• Locus (plural: loci): The specific physical location of a gene on a chromosome.

• Mendel's Laws: The principles of segregation and independent assortment are explained by the behavior of chromosomes during meiosis.

Chromosomal Basis of Gender

Sex Chromosomes and Gender Determination

In humans and other mammals, sex is determined by two types of sex chromosomes: X and Y. The presence or absence of these chromosomes determines biological sex.

• XX: Female

• XY: Male

• Hemizygous: Males are hemizygous for X-linked genes because they have only one X chromosome.

• Only the ends of the Y chromosome are homologous with the X chromosome, allowing for pairing during meiosis.

Gametes and Sex Chromosomes

• Eggs always carry an X chromosome (22 autosomes + X).

• Sperm can carry either an X or a Y chromosome (22 autosomes + X or Y).

X vs Y Chromosomes

Genes on Sex Chromosomes

• SRY gene: Located on the Y chromosome, this gene triggers male development.

• Sex-linked gene: Any gene located on a sex chromosome (X or Y).

• Y-linked genes: Genes found only on the Y chromosome; few in number.

• X-linked genes: Genes found on the X chromosome; many are unrelated to sex determination.

Inheritance Patterns of X-linked Genes

• X-linked genes follow specific inheritance patterns:

  • Females need two copies of a recessive allele to express an X-linked trait.

  • Males need only one copy (since they have only one X chromosome).

• X-linked recessive disorders are more common in males.

• Examples: Colorblindness, hemophilia, Duchenne muscular dystrophy.

X Inactivation in Female Mammals

Dosage Compensation and Barr Bodies

To balance gene expression between males and females, one X chromosome in each cell of a female is randomly inactivated during embryonic development. The inactive X condenses into a structure called a Barr body.

• Females heterozygous for X-linked genes are genetic mosaics, with different cells expressing different alleles.

Linked Genes and Genetic Recombination

Linked Genes

• Genes located on the same chromosome that tend to be inherited together are called linked genes.

• Each chromosome (except the Y) contains hundreds or thousands of genes.

Recombination of Unlinked Genes

• Offspring with a phenotype matching one of the parental phenotypes are called parental types.

• Genes that are far apart on the same chromosome can have a recombination frequency near 50%, behaving as if they are unlinked.

• Natural selection acts on genetic variation produced by recombination.

Chromosomal Alterations and Aneuploidy

Nondisjunction

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

• Meiosis I nondisjunction: All gametes are abnormal.

• Meiosis II nondisjunction: Half the gametes are normal, half are abnormal.

Aneuploidy and Polyploidy

• Monosomic zygote: Has only one copy of a particular chromosome.

• Trisomic zygote: Has three copies of a particular chromosome.

• Polyploidy: Condition in which an organism has more than two complete sets of chromosomes.

Sex Chromosome Aneuploidies

Condition	Karyotype	Phenotype
Triple X	XXX	Healthy female, usually no unusual physical conditions
Klinefelter syndrome	XXY	Male, often with some feminized traits
Turner syndrome	X (Monosomy X)	Female, only survivable monosomy in humans

Genomic Imprinting

Parent-of-Origin Effects

For some mammalian traits, the phenotype depends on which parent passed along the allele. This phenomenon is called genomic imprinting and involves the silencing of certain genes depending on their parental origin. Only a small number of mammalian genes are affected by imprinting.