• The Detection of Mutations in Human Chromosome 8
  
• Design a Chromosome
  
• Identify a family tree through the chromosome 16 Alu allele of each member and understand the mechanism that passes on the gene
  

Figure 1: Chromosome. (1) Chromatid. One of the two identical parts of the chromosome after S phase. (2) Centromere. The point where the two chromatids touch, and where the microtubules attach. (3) Short arm (4) Long arm.

A chromosome is a large macromolecule into which DNA is normally packaged in a cell. Minimally, it is a very long, continuous piece of DNA (a single DNA molecule), which contains many genes, regulatory elements and other intervening nucleotide sequences.

The word chromosome comes from the Greek χρώμα (chroma, color) and σώμα (soma, body).

In the chromosomes of eukaryotes, the uncondensed DNA exists in a quasi-ordered structure inside the cell nucleus, where it wraps around histones (structural proteins, Fig. 1), forming a composite material called chromatin. Each chromosome has two arms, the shorter one called p arm (from the French petit, small) and the longer one q arm (q follows p in the Latin alphabet). During mitosis (cell division), the chromosomes are condensed and a spindle composed of microtubules is formed. Microtubules self-assemble from dimers of alpha and beta tubulin. They attach to chromosomes at specialized structures called kinetochores, one of which is present on each sister chromatid. Sister chromatids are attached at an area called the centromere (not necessarily at the center of the chromosome). A special DNA base sequence in the region of the kinetochores provides, along with special proteins, longer-lasting attachment in this region. This is the only natural context in which individual chromosomes are visible with an optical microscope.

Prokaryotes do not possess histones or nuclei. In its relaxed state, the DNA can be accessed for transcription, regulation, and replication.

History

Chromosomes were first observed in plant cells by Swiss botanist Karl Wilhelm von Nägeli in 1842, and independently in Ascaris worms by Belgian scientist Edouard Van Beneden (1846-1910). The use of basophilic aniline dyes was a fundamentally new technique for effectively staining the chromatin material in the nucleus. Their behavior in animal (salamander) cells was later described in detail by German anatomist Walther Flemming, the discoverer of mitosis, in 1882. The name was invented later by another German anatomist, Heinrich von Waldeyer.

Chromosomes in plants, yeast and animals

Eukaryotes (cells with nuclei such as plants, yeast, and animals) possess multiple linear chromosomes contained in the cell's nucleus. Each chromosome has one centromere, with one or two arms projecting from the centromere.

Chromosomes in bacteria

Bacteria have a single circular chromosome. Bacterial DNA also exists as plasmids which are circular pieces of DNA that can be transmitted between bacteria. Antibiotic resistance genes are often carried on plasmids and can thus spread between different bacteria. The distinction between plasmids and chromosomes is poorly defined, though size and necessity are generally taken into the account. Bacterial chromosomes initiate replication and one origin of replication.

Bacterial chromosomes tend to be tethered to the plasma membrane of the bacteria. In molecular biology application, this allows for its isolation from plasmid DNA by centrifugation of lysed bacteria and pelleting of membranes (and the attached DNA).

Chromatin

Two types of chromatin can be distinguished:

• Euchromatin, which consists of DNA that is active, e.g., expressed as protein.
• Heterochromatin, which consists of mostly inactive DNA. It seems to serve structural purposes during the chromosomal stages. Heterochromatin can be further distinguished into two types:
  • Constitutive heterochromatin, which is never expressed. It is located around the centromere and usually contains repetitive sequences.
  • Facultative heterochromatin, which is sometimes expressed.

Figure 2: Different levels of DNA condensation. (1) Double-strand DNA. (2) Chromatin strand (DNA with histones). (3) Chromatin during interphase with centromere. (4) Condensed chromatin during prophase. (Two copies of the DNA molecule are now present) (5) Chromosome during metaphase.

In the very early stages of mitosis, the chromatin strands become more and more condensed. They cease to function as accessible genetic material and become a compact transport form. Eventually, the two matching chromatids (condensed chromatin strands) become visible as a chromosome, linked at the centromere. Long microtubules are attached at the centromere and two opposite ends of the cell. During mitosis, the microtubules pull the chromatids apart, so that each daughter cell inherits one set of chromatids. Once the cells have divided, the chromatids are uncoiled and can function again as chromatin. In spite of their appearance, chromosomes are highly structured which enables these giant DNA structures to be contained within a cell nucleus (Fig. 2).

Number of chromosomes in various species

Normal members of a particular species all have the same number of chromosomes (see the table).

Asexually reproducing species have one set of chromosomes, which is the same in all body cells.

Sexually reproducing species have somatic cells (body cells), which are diploid [2n] having two sets of chromosomes, one from the mother and one from the father. Gametes, reproductive cells, are haploid [n]: they have one set of chromosomes. Gametes are produced by meiosis of a diploid germ line cell. During meiosis, the matching chromosomes of father and mother can exchange small parts of themselves (crossover), and thus create new chromosomes that are not inherited solely from either parent. When a male and a female gamete merge (fertilization), a new diploid organism is formed.

Some animal and plant species are polyploid [Xn]: they have more than two sets of chromosomes. Agriculturally important plants such as tobacco or wheat are often polyploid compared to their ancestral species. Wheat has a haploid number of seven chromosomes, still seen in some cultivars as well as the wild progenitors. The more common pasta and bread wheats are polyploid having 28 (tetraploid) and 42 (hexaploid) chromosomes compared to the 14 (diploid) chromosomes in the wild wheat^[1].

Historical note: In 1921, Theophilus Painter claimed, based on his observations, that human sex cells had 24 pairs of chromosomes, giving humans 48 chromosomes total. It wasn't until 1955 that the number of pairs was clearly shown to be 23.

Karyotype

Figure 3: Karyotype of a human male

To determine the (diploid) number of chromosomes of an organism, cells can be locked in metaphase in vitro (in a reaction vial) with colchicine. These cells are then stained (the name chromosome was given because of their ability to be stained), photographed and arranged into a karyotype (an ordered set of chromosomes, Fig. 3), also called karyogram. Like many sexually reproducing species, humans have special gonosomes (sex chromosomes, in contrast to autosomes). These are XX in females and XY in males. In females, one of the two X chromosomes is inactive and can be seen under a microscope as Barr bodies.

Human

• † Human Genome Project goals called for determination of only the euchromatic portion of the genome. Telomeres, centromeres, and other heterochromatic regions have been left undetermined, as have a small number of unclonable gaps. [1]

Chromosomal aberrations

Main articles: Chromosome abnormalities and aneuploidy

In Down syndrome, chromosome 21 is affected

Some chromosome abnormalities do not cause disease in carriers, such as translocations, or chromosomal inversions, although they may lead to a higher chance of having a child with a chromosome disorder. Abnormal numbers of chromosomes or chromosome sets, aneuploidy, may be lethal or give rise to genetic disorders. Genetic counseling is offered for families that may carry a chromosome rearrangement.

The gain or loss of chromosome material can lead to a variety of genetic disorders. Examples include:

• Cri du chat, which is caused by the deletion of part of the short arm of chromosome 5. "Cri du chat" means "cry of the cat" in French, and the condition was so-named because affected babies make high-pitched cries that sound like a cat. Affected individuals have wide-set eyes, a small head and jaw and are moderately to severely mentally retarded and very short.
• Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4. It is characterized by severe growth retardation and severe to profound mental retardation.
• Down syndrome, usually is caused by an extra copy of chromosome 21 (trisomy 21). Characteristics include decreased muscle tone, asymmetrical skull, slanting eyes and mild to moderate mental retardation.
• Edward's syndrome, which is the second most common trisomy after Down syndrome. It is a trisomy of chromosome 18. Symptoms include mental and motor retardation and numerous congenital anomalies causing serious health problems. Ninety percent die in infancy; however, those who live past their first birthday usually are quite healthy thereafter. They have a characteristic hand appearance with clenched hands and overlapping fingers.
• Patau Syndrome, also called D-Syndrome or trisomy-13. Symptoms are somewhat similar to those of trisomy-18, but they do not have the characteristic hand shape.
• Idic15, abbreviation for Isodicentric 15 on chromosome 15; also called the following names due to various researches, but they all mean the same; IDIC(15), Inverted dupliction 15, extra Marker, Inv dup 15, partial tetrasomy 15
• Jacobsen syndrome, also called the terminal 11q deletion disorder.[2] This is a very rare disorder. Those affected have normal intelligence or mild mental retardation, with poor expressive language skills. Most have a bleeding disorder called Paris-Trousseau syndrome.
• Klinefelter's syndrome (XXY). Men with Klinefelter syndrome are usually sterile, and tend to have longer arms and legs and to be taller than their peers. Boys with the syndrome are often shy and quiet, and have a higher incidence of speech delay and dyslexia. During puberty, without testosterone treatment, some of them may develop gynecomastia.
• Turner syndrome (X instead of XX or XY). In Turner syndrome, female sexual characteristics are present but underdeveloped. People with Turner syndrome often have a short stature, low hairline, abnormal eye features and bone development and a "caved-in" appearance to the chest.
• XYY syndrome. XYY boys are usually taller than their siblings. Like XXY boys and XXX girls, they are somewhat more likely to have learning difficulties.
• Triple-X syndrome (XXX). XXX girls tend to be tall and thin and are often shy. They have a higher incidence of dyslexia.
• Small supernumerary marker chromosome. This means there is an extra, abnormal chromosome. Features depend on the origin of the extra genetic material. Cat-eye syndrome and isodicentric chromosome 15 syndrome (or Idic15) are both caused by a supernumerary marker chromosome, as is Pallister-Killian syndrome.

A detailed graphical display of all human chromosomes and the diseases annotated at the correct spot may be found at [3].

See also

• Locus (explains gene location nomenclature)
• Sex-determination system
  • XY sex-determination system
    • X chromosome
      • X-inactivation
    • Y chromosome
      • Y-chromosomal Adam
      • Y-chromosomal Aaron
• Genetic genealogy
  • Genealogical DNA test
• Genetic deletion
• List of number of chromosomes of various organisms

External links

• What Can Our Chromosomes Tell Us?,an accessible and comprehensive look at chromosomes, from the University of Utah's Genetic Science Learning Center
• Random Orientation of Chromosomes Animation
• Try making a karyotype yourself, from the University of Utah's Genetic Science Learning Center
• Kimballs Chromosome pages
• Chromosome News from Genome News Network
• European Chromosome 11q Network
• Eurochromnet, European network for Rare Chromosome Disorders on the Internet
• http://www.ensembl.org Ensembl project, presenting chromosomes, their genes and syntenic loci graphically via the web
• Genographic Project
• A Yahoo! group for Isodicentric 15

References

1. ^ Sakamura, T. (1918), Kurze Mitteilung uber die Chromosomenzahlen und die Verwandtschaftsverhaltnisse der Triticum-Arten. Bot. Mag., 32: 151-154.