2021_L12 Chromosome structure & function

Dr. Ahmad Tarmidi Sailan - Chromosome Structures and Functions

References

  • Principles of Textbook of Genetics Biochemistry, Eighth Edition with Clinical Correlations

  • Lippincott's Sixth Edition Illustrated

  • Authors: Robert K. Murray, David A. Bender, Allan D. Marks

  • Clinical editors: Kathleen M. Botham, Peter J. Kennelly, Richard A. Harvey, Victor W. Rodwell, Pamela C. Champe, P. Anthony Weil, Michael Lieberman

Objectives

  • Explain the role of chromosomes in cell division.

  • Describe the structure of chromosomes.

  • Describe nucleosomes.

  • Explain variations of chromosomes (structures and numbers) with examples.

Cell Division Overview

Cell Cycles

  • Mitosis and Meiosis.

Types of Cell Division

  • Mitosis: Division of the nucleus.

  • Cytokinesis: Division of the cytoplasm.

  • Meiosis: Cell division that results in gametes.

    • Produces non-identical daughter cells.

    • Results in 1 set of chromosomes.

    • Occurs only in gonads.

    • Fertilization restores full chromosome number.

Reasons for Cell Division

  • Reproduction: Formation of new organisms.

  • Growth: Development from zygote to adult.

  • Repair/Renewal: Mitosis repairs damaged tissues and regenerates high turnover cells (e.g., blood and skin).

Frequency of Cell Division by Cell Type

  • Skin cells: Frequent division throughout life.

  • Liver cells: Have the ability to divide but do so when needed.

  • Nerve and muscle cells: Do not divide in mature adults.

Differences Between Mitosis and Meiosis

Mitosis

  • Function: Growth, repair, and asexual reproduction.

  • Occurs continuously throughout the cell life cycle.

  • Location: Somatic cells.

  • Division: One division produces two genetically identical daughter cells, diploid (2N).

Meiosis

  • Function: Sexual reproduction and generation of new gene combinations.

  • Location: Gamete cells (e.g., sperm and eggs).

  • Division: Two divisions produce four genetically different daughter cells, haploid (1N).

Eukaryotic Chromosome Structure

  • DNA is organized in a higher structure within the nucleus.

  • Double-stranded DNA is wound around histones to form nucleosomes.

Nucleosome

  • Chromatin: Long linear DNA molecule containing thousands of genes.

  • Further condensation forms chromosomes.

  • Histones: Proteins that maintain the structure of chromosomes.

    • DNA wraps twice around histone octamer.

Further DNA Condensation Process

  • Nucleosome fibers condense to form chromatin fibers.

  • DNA is folded about 50 times through supercoiling, stabilizing fibers with histones.

  • Chromosomes form during the mitotic phase (M phase).

Non-Dividing vs Dividing Chromosomes

  • Non-dividing chromosomes appear as long, thin chromatin fibers; indistinguishable under microscopes.

  • Dividing chromosomes become shorter and thicker, highly coiled, and folded for visibility during metaphase.

Chromatids

  • After duplication, chromosomes consist of two sister chromatids, held together by a centromere.

  • In humans, there are 23 pairs of chromosomes.

Chromosome Variation

Cri-du-chat Syndrome

  • Associated with deletion of part of the short arm of chromosome 5.

  • Features microcephaly and a characteristic cat-like cry.

Karyotype Techniques

  • G-staining: Staining technique showing bands along chromosomes.

  • C-staining: Highlights centromere regions.

  • R-staining: Reverse staining to identify chromosomes.

  • Q-staining: Quinacrine staining producing positive and negative bands.

Chromosome Number Variations

Down Syndrome

  • Caused by Trisomy 21 (47,+21).

    • Main phenotypic characteristics: Short stature, broad head, mental retardation.

Turner Syndrome

  • Caused by 45,X karyotype (only one X chromosome).

    • Features: Short stature, infertility, webbing of neck.

Klinefelter Syndrome

  • Caused by 47,XXY karyotype (extra X chromosome).

    • Features: Subfertility, breast development, long limbs.

Nondisjunction Events

  • First meiotic nondisjunction results in no normal gametes.

  • Second meiotic nondisjunction may produce gametes with identical chromosomes.

Diagnosis via Amniocentesis

  • Procedure for sample collection for prenatal chromosomal and biochemical analysis.