Sex Chromosomes and Lyon Hypothesis

Sex Chromosomes, Barr Body and Lyon Hypothesis

• Sex is determined at fertilization
• Sexual differences emerge during the 7th week
• Sex is influenced by genetic and environmental factors
• Females (generally XX) lack a Y chromosome
• Males (generally XY) possess a Y chromosome

Objectives

• Understand X inactivation
• Determine the number of Barr bodies in a human cell
• Explain the Lyon hypothesis
• Recognize the advantages of Barr body determination

Matters of Sex

• Aneuploidy: Having too many or too few chromosomes compared to normal
• Monosomy: Possessing only one copy of a chromosome
• Monosomy (with the exception of the X chromosome) is incompatible with life

X Chromosome Dosage

• Females (XX) have twice the X-linked genes of males (XY)
• X-inactivation: A mechanism to create equal amounts of X gene products in both sexes
• One X chromosome is inactivated to equalize gene products

X Chromosomes

• Demonstrated by culturing cells with different karyotypes (e.g., XY, XX, XXX, XXXX)
• Enzyme levels encoded by the X chromosome are observed

X-linked Gene (G6PD)

• Located on the X chromosome
• Codes for an enzyme (glucose-6-phosphate dehydrogenase) that breaks down sugar
• Females produce the same amount of G6PD enzyme as males
• XXY and XXX individuals have a normal amount of G6PD

Conclusion

• Only one X chromosome is active in a given cell; the other is inactive
• In some cells, the paternal allele is expressed, while in others, the maternal allele is expressed
• In XXX and XXXX females and XXY males, only one X chromosome is activated; the rest are inactivated
• X inactivation is random

Conclusion (cont.)

• XXX embryos survive due to inactivation of two X chromosomes, resulting in one active X
• Trisomy 21 (Down syndrome) cannot inactivate the extra chromosome 21
• Only the X chromosome can be inactivated

Three Types of Chromatin

• Euchromatin: True chromatin; possesses active genes
• Heterochromatin: Stains darker than euchromatin; contains highly repetitive DNA with few active genes; usually found around centromeres and telomeres
• Facultative Heterochromatin: Active in some cells like euchromatin but inactive like heterochromatin in others

Facultative Heterochromatin

• A mechanism to shut off a portion or entire chromosome, preventing gene expression
• Active X chromosomes behave like euchromatin, with active genes transcribed
• Inactive X chromosomes behave like heterochromatin

The cell inactivates one X chromosome by converting it to heterochromatin (inactive DNA). This inactive DNA creates the Barr body, which appears as a dark staining structure.

Lyon Hypothesis

• Proposed by Mary Lyon in 1961 to describe X inactivation
• Consists of five tenants:
• Condensed X chromosome is genetically inactive
• X inactivation occurs early in embryo development (around 32 cells/ 1-2 days post-fertilization)
• At this stage, one of the X chromosomes is randomly inactivated in each cell
• Inactivation is mitotically stable (remains inactivated during cell divisions)
• The net effect equalizes phenotypes in males and females for X-linked genes

Human Chromosomes (Additional Detail)

• One X chromosome in females is inactivated early in embryonic development.
• The inactivated X chromosome can be visually identified as a Barr body.

Barr Body

• Present in somatic XX nuclei but not in XY nuclei
• One X chromosome is converted to heterochromatin (Barr body) in females to make the amounts equal
• Females always have one active X and one inactive X in a given cell
• Visible in epithelial cells and blood leucocytes as darkly stained or drum-stick-shaped structures, respectively

X Inactivation

• Random inactivation of one X chromosome in each cell
• Results in males and females having similar levels of expression for X-linked genes

Demonstration of Barr Body

• Visible in epithelial cells (buccal smear)
• Visible in blood leukocytes (sex chromatin appears as drum-stick shaped)

Significance of Barr Body

• Used to diagnose genetic sex in doubtful cases (e.g., hermaphroditism)
• Used to study sex chromosome abnormalities
• Used to diagnose abnormal sexual development and maturation
• Used to diagnose infertility, primary amenorrhea, and spontaneous abortion
• Used to identify fetal sex by staining cells from amniotic fluid

This quiz explores the concepts of sex determination, X inactivation, and the Lyon hypothesis. You'll learn about Barr bodies, aneuploidy, and X chromosome dosage. Test your understanding of genetic and environmental influences on sexual differences.