Chromosomes

Composition

• many copies of 5 kinds of histones. Histones are proteins rich in lysine and arginine residues and thus positively-charged. For this reason they bind tightly to the negatively-charged phosphates in DNA.
• a small number of copies of many different kinds of non-histone proteins. Most of these are transcription factors that regulate which parts of the DNA will be transcribed into RNA.

Structure

• For most of the life of the cell, chromosomes are too elongated and tenuous to be seen under a microscope.
• Before a cell gets ready to divide by mitosis, each chromosome is duplicated (during S phase of the cell cycle).
• As mitosis begins, the duplicated chromosomes condense into short (~ 5 µm) structures which can be stained and easily observed under the light microscope.
• These duplicated chromosomes are called dyads.

• When first seen, the duplicates are held together at their centromeres. In humans, the centromere contains 1–10 million base pairs of DNA. Most of this is repetitive DNA: short sequences (e.g., 171 bp) repeated over and over in tandem arrays.
• While they are still attached, it is common to call the duplicated chromosomes sister chromatids, but this should not obscure the fact that each is a bona fide chromosome with a full complement of genes.
• The kinetochore is a complex of >80 different proteins that forms at each centromere and serves as the attachment point for the spindle fibers that will separate the sister chromatids as mitosis proceeds into anaphase.
• The shorter of the two arms extending from the centromere is called the p arm; the longer is the q arm.
• Staining with the trypsin-giemsa method reveals a series of alternating light and dark bands called G bands.
• G bands are numbered and provide "addresses" for the assignment of gene loci.

  Diagram of p and q arms, G bands, and gene loci

Chromosome Numbers

• All animals have a characteristic number of chromosomes in their body cells called the diploid (or 2n) number.
• These occur as homologous pairs, one member of each pair having been acquired from the gamete of one of the two parents of the individual whose cells are being examined.
• The gametes contain the haploid number (n) of chromosomes.

(In plants, the haploid stage takes up a larger part of its life cycle - Link)

Karyotypes

The complete set of chromosomes in the cells of an organism is its karyotype. It is most often studied when the cell is at metaphase of mitosis and all the chromosomes are present as dyads.

• 22 pairs of autosomes
• 1 pair of X chromosomes

• the same 22 pairs of autosomes
• one X chromosome
• one Y chromosome

(A gene on the Y chromosome designated SRY is the master switch for making a male.)

The X and Y chromosomes are called the sex chromosomes.)

Above is a human karyotype (of which sex?). It differs from a normal human karyotype in having an extra #21 dyad. As a result, this individual suffered from a developmental disorder called Down Syndrome. The inheritance of an extra chromosome, is called trisomy, in this case trisomy 21. It is an example of aneuploidy

FISH

Location of the gene for muscle glycogen phosphorylase on human chromosome 11

DNA Content

The molecule of DNA in a single human chromosome ranges in size from 50 x 10⁶ nucleotide pairs in the smallest chromosome (stretched full-length this molecule would extend 1.7 cm) up to 250 x 10⁶nucleotide pairs in the largest (which would extend 8.5 cm).

Stretched end-to-end, the DNA in a single human diploid cell would extend over 2 meters.

In the intact chromosome, however, this molecule is packed into a much more compact structure. [Link]. The packing reaches its extreme during mitosis when a typical chromosome is condensed into a structure about 5 µm long (a 10,000-fold reduction in length).

Structural Abnormalities of Chromosomes

There are a number of agents — both exogenous (e.g., ionizing radiation) and endogenous (e.g., crossing over in meiosis) — that break the double helix of DNA. Often the cell rejoins the broken ends successfully (by Nonhomologous End-Joining) and all is well. However, occasional failures can result in changes in the structure of the chromosome.

Insertions and Deletions (Indels)

Extra base pairs may be added (insertions — LINK) or removed (deletions — LINK) from the DNA of a gene. The number can range from one to thousands. Collectively, these mutations are called indels.

Duplications

Duplications are a doubling of a section of the chromosome. During meiosis, crossing over between sister chromatids that are out of alignment can produce one chromatid with a duplicated segment and the other with a corresponding deletion. MORE

Translocations

• The break may occur within a gene destroying its function.
• Translocated genes may come under the influence of different promoters and enhancers so that their expression is altered. The t(8;14) translocation in Burkitt's lymphoma (figure) is an example. [More]
• The breakpoint may occur within a gene creating a hybrid gene. This may be transcribed and translated into a protein with an N-terminal of one normal cell protein coupled to the C-terminal of another. Examples
  • The Philadelphia chromosome (Ph¹) found so often in the leukemic cells of patients with chronic myelogenous leukemia (CML) is the result of a translocation between chromosomes 9 and 22 which produces a compound gene (BCR-ABL). More
  • a translocation between chromosomes 18 and 14 causes B-cell leukemia [Link]

Aneuploidy

• homologues during meiosis I or
• sister chromatids during meiosis II