chromosome structure and organisation, including the role of histone proteins, sex chromosomes and autosomes, homologous pairs and karyotypes as a visual representation of chromosomes used to identify chromosomal abnormalities

What this dot point is asking

VCAA wants the structure of chromosomes (DNA + histones), the distinction between autosomes and sex chromosomes, the meaning of a homologous pair, and the use of a karyotype to identify chromosomal abnormalities.

The answer

Chromosome structure

A chromosome is one continuous DNA molecule packed with proteins, found in the nucleus of a eukaryotic cell. If stretched out, the DNA in a single human chromosome would be several centimetres long; it has to be packed thousands-of-times tighter to fit into a nucleus a few micrometres across.

Packaging happens through several levels:

1. Double helix. Two complementary DNA strands wound together (about 2 nm wide).
2. Nucleosomes. DNA wraps about 1.65 times around a core of 8 histone proteins (two each of H2A, H2B, H3 and H4). This forms the "beads on a string" of chromatin (about 11 nm wide).
3. 30-nm fibre. Linker histone H1 helps the nucleosomes coil into a denser fibre.
4. Loops and scaffolds. The fibre is organised into loops on a non-histone protein scaffold.
5. Condensed chromosome. During mitosis and meiosis, the chromatin condenses into the X-shaped chromosomes visible under a light microscope (about 700 nm wide).

In interphase, chromosomes are dispersed as chromatin, accessible for transcription and replication. During cell division, they condense into visible chromosomes that can be separated mechanically by the spindle.

After S-phase DNA replication, each chromosome consists of two identical sister chromatids joined at the centromere. The centromere is the attachment point for spindle fibres in mitosis and meiosis.

Autosomes and sex chromosomes

Human cells contain 46 chromosomes organised as 23 pairs.

• Autosomes: pairs 1 to 22 (44 chromosomes). These carry most of the genes and look identical in males and females.
• Sex chromosomes: pair 23. In humans, XX in females and XY in males. The X chromosome is large and contains around 800 genes. The Y chromosome is small (around 50 genes) and carries the SRY gene that triggers male development.

Other species have different sex-determination systems: birds use ZW (males ZZ, females ZW); some reptiles use temperature; bees use haploid-diploid.

Homologous chromosomes

A homologous pair is the two chromosomes in one pair (such as the two copies of chromosome 7, or X and X in a female). They:

• Are the same size and shape.
• Carry the same genes at the same loci.
• May carry the same allele or different alleles at each locus.
• Came one from each parent (one maternal, one paternal).

The two X chromosomes in a female are fully homologous. The X and Y in a male are not fully homologous: they pair only at the small pseudoautosomal regions. This is why sex-linked inheritance has different rules.

Diploid (2n) means having two copies of each chromosome (one homologous pair per gene). Haploid (n) means having one copy of each chromosome. Human somatic cells are diploid; gametes (sperm and egg) are haploid.

Karyotypes

A karyotype is a visual display of all the chromosomes in a cell, arranged by size, banding pattern and centromere position. To prepare one:

1. Cells are collected (typically white blood cells, or fetal cells from amniocentesis or chorionic villus sampling).
2. Cells are encouraged to divide; division is stopped at metaphase, when chromosomes are most condensed and visible.
3. Cells are spread on a slide, stained (commonly with Giemsa for G-banding), photographed.
4. The chromosomes are sorted by image: largest (chromosome 1) to smallest (chromosome 22), then the sex chromosomes.

The output is the familiar paired-up display.

What a karyotype can detect

• Sex. XX = female, XY = male.
• Numerical abnormalities (aneuploidy): the wrong number of one chromosome, almost always from non-disjunction in meiosis. Examples:
  • Down syndrome: trisomy 21 (three copies of chromosome 21), incidence about 1 in 700 births; risk rises with maternal age.
  • Edwards syndrome: trisomy 18.
  • Patau syndrome: trisomy 13.
  • Turner syndrome: XO (a single X, no second sex chromosome). Female phenotype with infertility and shorter stature.
  • Klinefelter syndrome: XXY. Male phenotype with reduced fertility.
  • Triple X: XXX.
• Structural abnormalities:
  • Deletions: a piece of chromosome is missing.
  • Duplications: an extra copy of a region.
  • Inversions: a section flipped end-to-end.
  • Translocations: a piece swapped between two non-homologous chromosomes (such as the Philadelphia chromosome in chronic myeloid leukaemia).

Karyotype notation

The convention: total chromosome number, comma, sex chromosomes, comma, any abnormalities.

• Normal female: 46, XX.
• Normal male: 46, XY.
• Down syndrome female: 47, XX, +21.
• Turner syndrome: 45, X.

Worked example

A karyotype from an amniocentesis reads 47, XX, +21. The total chromosome count is 47, the sex chromosomes are XX (female), and the +21 indicates trisomy 21 (an extra chromosome 21). This is Down syndrome. The most likely cause is non-disjunction at meiosis I in the mother: the homologous chromosome 21 pair failed to separate, producing an egg with two copies of chromosome 21 instead of one; fertilisation by a normal sperm gave a zygote with three.

Common traps

Confusing homologous chromosomes with sister chromatids. Homologous chromosomes: a pair from two parents, same genes, possibly different alleles. Sister chromatids: two identical copies of one chromosome made by S-phase DNA replication, joined at the centromere.

Saying the X and Y are "the same". They are not. Y is much smaller, has fewer genes, and pairs with X only at small regions.

Saying humans have "23 chromosomes". Humans have 46 chromosomes in 23 pairs (somatic cells) and 23 chromosomes (gametes).

Saying karyotypes show gene mutations. Karyotypes show chromosome-level changes (number, large rearrangements). Single-gene mutations are not visible on a karyotype; they need DNA sequencing or PCR.

Forgetting that non-disjunction can happen in either meiosis I or meiosis II. I: the homologous pair fails to separate. II: the sister chromatids fail to separate.

In one sentence

A chromosome is a length of DNA wound around histones into chromatin, condensed during cell division into the visible X-shape; humans have 46 chromosomes in 23 pairs (22 autosomal pairs plus XX in females or XY in males), and a karyotype is a visual display of these chromosomes used to identify numerical abnormalities (such as trisomy 21 in Down syndrome) and structural abnormalities (deletions, duplications, inversions, translocations).