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 Chromosomes

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تاريخ التسجيل : 22/06/2009
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مُساهمةموضوع: Chromosomes   السبت يونيو 14, 2014 12:05 am

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DNA

DNA is a polymer made from many thousands of nucleotides strung together

Nucleotide is made of a
Deoxyribose (5 carbon Sugar)
Phosphate group
Base (A,C,G,T)

DNA and its Building Nucleotides:
Guanine (G), Adenine (A),
Cytosine (C), Thymine (T).


The amount of (G) equals the amount of (C);
and the amount of (A) equals the amount of (T)


A-T two hydrogen bonds
G-C three hydrogen bonds

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What is a chromosome?

They were given the name chromosome (Chromo = color; Soma = body) due to their marked affinity for basic dyes.

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences.

Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.

Chromosomal DNA encodes most or all of an organism's genetic information; some species also contain plasmids or other extra-chromosomal genetic elements.

Metaphase: Chromosomes are the most easily observed and studied during metaphase when they are very thick, quite short and well spread in the cell.

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Prokaryotic chromosome

Prokaryotic cells (bacteria) contain their chromosome as circular  DNA.  Usually the entire genome is a single circle, but often there are extra circles called plasmids. 

The bundled DNA is called the nucleoid.  It concentrates the DNA in part of the cell, but it is not separated by a nuclear membrane as in eukaryotes.

The DNA is accessible to enzymes that make RNA and protein. 

In the bacterial cell, the DNA gets transcribed to RNA, and the RNA gets translated to protein before it is even completed.

Plasmid

A plasmid is a small ring of DNA that carries accessory genes. Usually these genes are for antibiotic resistance!

Plasmids are double-stranded and, in many cases, circular. Plasmids usually occur naturally in bacteria, but are sometimes found in eukaryotic organisms

Plasmids used in genetic engineering are called vectors. Plasmids serve as important tools in genetics and biotechnology labs, where they are commonly used to multiply (make many copies of) or express particular genes

Another major use of plasmids is to make large amounts of proteins. In this case, researchers grow bacteria containing a plasmid harboring the gene of interest.

Just as the bacterium produces proteins to confer its antibiotic resistance, it can also be induced to produce large amounts of proteins from the inserted gene. This is a cheap and easy way of mass-producing a gene or the protein it then codes for.


Chromosomes in eukaryotes

Eukaryotic cells contain their DNA within the nuclear membrane.
The DNA double helix is bound to proteins called histones.  The histones have  positively charged (basic) amino acids to bind the negatively charged (acidic) DNA. 

The DNA is wrapped around the histone core of eight protein subunits, forming the nucleosome.   The nucleosome is clamped by histone H1 (About 200 base pairs (bp) of DNA coil around one histone). 

There are 5 major types of histones: H1, H2A, H2B, H3, and H4 – which are very similar among different sp of eukaryotes.

In mitosis, the chromosomes appear as the thick rod-shaped bodies which can be stained and visualized under light microscopy.


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Chromatin

Chromatin is the complex of DNA and protein found in the eukaryotic nucleus, which packages chromosomes. The structure of chromatin varies significantly between different stages of the cell cycle, according to the requirements of the DNA.

Interphase chromatin

During interphase (the period of the cell cycle where the cell is not dividing), two types of chromatin can be distinguished:
1-Euchromatin, which consists of DNA that is active, e.g., being expressed as protein.
2-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:
A-Constitutive heterochromatin, which is never expressed. It is located around the centromere.
B-Facultative heterochromatin, which is sometimes expressed.


Human chromosomes

Chromosomes in humans can be divided into two types: autosomes and sex chromosomes.

Certain genetic traits are linked to a person's sex and are passed on through the sex chromosomes.

The autosomes contain the rest of the genetic hereditary information. All act in the same way during cell division.

Human cells have 23 pairs of chromosomes (22 pairs of autosomes and one pair of sex chromosomes), giving a total of 46 per cell.


Centromeres and Telomeres

Centromeres and telomeres are two essential features of all eukaryotic chromosomes.

Each provide a unique function i.e., absolutely necessary for the stability of the chromosome.

Centromeres are required for the segregation of the chromosomes during meiosis and mitosis.

Telomeres provide terminal stability to the chromosome and ensure its survival

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The region where two sister chromatids of a chromosome appear to be joined or “held together” during metaphase is called Centromere

When chromosomes are stained they typically show a dark-stained region that is the centromere.

During mitosis, the centromere that is shared by the sister chromatids must divide so that the chromatids can migrate to opposite poles of the cell.

On the other hand, during the first meiotic division the centromere of sister chromatids must remain intact

whereas during meiosis II they must act as they do during mitosis.
Therefore the centromere is an important component of chromosome structure and segregation.

As a result, centromeres are the first parts of chromosomes to be seen moving towards the opposite poles during anaphase.


Kinetochore

Within the centromere region, most species have several locations where spindle fibers attach, and these sites consist of DNA as well as protein.

The actual location where the attachment occurs is called the kinetochore and is composed of both DNA and protein.

DNA sequence within these regions is called CEN DNA.

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Typically CEN DNA is about 120 base pairs long and consists of several sub-domains, CDE-I, CDE-II and CDE-III.
Mutations in the first two sub-domains have no effect upon segregation, but a point mutation in the CDE-III sub-domain completely eliminates the ability of the centromere to function during chromosome segregation.

Therefore CDE-III must be actively involved in the binding of the spindle fibers to the centromere.


Telomere

The two ends of a chromosome are known as telomeres and they are required for the replication and stability of the chromosome.

The centromere divides each chromosome into two regions: the small one, which is the p region, and the big one (q region)

As a convection, the p region is represented in the upper part of the image , while the q region is the bottom part

When telomeres are damaged or removed due to chromosome breakage, the damaged chromosome ends can readily fuse or unite with broken ends of other chromosome.



Thus the ends of broken chromosomes are sticky, whereas the normal end is not sticky, suggesting the ends of chromosomes have unique features.


Numbers of chromosomes

Constant for each cell in the body (except sex cells which only have half sets).
Constant throughout the life of an individual (you don’t lose or gain chromosomes)
Constant for all members of a species

Normally, all the individuals of a species have the same number of chromosomes.

Presence of a whole sets of chromosomes is called euploidy.
It includes haploids, diploids, triploids, tetraploids etc.

Gametes normally contain only one set of chromosome – this number is called Haploid (1n)
Somatic cells usually contain two sets of chromosome and is called Diploid (2n)


When a change in the chromosome number does not involve entire sets of chromosomes, but only a few of the chromosomes - is Aneuploidy.
Monosomics (2n-1) Trisomics (2n+1)
Nullisomics (2n-2) Tetrasomics (2n+2)


karyotypes

A karyotype is the number and appearance of chromosomes in the nucleus of a eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism

Karyotypes can be used for many purposes; such as, to study chromosomal aberrations, cellular function, and to gather information about past evolutionary events

The basic number of chromosomes in the somatic cells of an individual or a species is called the somatic number and is designated 2n. Thus, in humans 2n = 46, while in the  sex cells the chromosome number is n (humans: n = 23).

So, in normal diploid organisms, autosomal chromosomes are present in two copies.

Polyploid cells have multiple copies of chromosomes and haploid cells have single copies.


Identifying chromosomes

A karyotype is an organized profile of a person's chromosomes. In a karyotype, chromosomes are arranged and numbered by size, from largest to smallest.

This arrangement helps scientists quickly to identify chromosomal alterations that may result in a genetic disorder

To make a karyotype, scientists take a picture of someone's chromosomes, cut them out and match them up using size, banding pattern and centromere position as guides


Making a Karyotype

1-First the chromosomes are stained

2-Then they are organized by height and centromere location


Karyotypes Nomenclature

Total number of chromosomes, then the makeup of the sex chromosomes and any extra chromosomes
Example
46, XX
46, XY
47, XY, +21


Chromosomal Aberrations

The somatic (2n) and gametic (n) chromosome numbers of a species ordinarily remain constant.
This is due to the extremely precise mitotic and meiotic cell division.

Somatic cells of a diploid species contain two copies of each chromosome, which are called homologous chromosome. Their gametes, therefore contain only one copy of each chromosome, that is they contain one chromosome complement or genome.

Each chromosome of a genome contains a definite numbers and kinds of genes, which are arranged in a definite sequence.

Sometime due to mutation or spontaneous (without any known causal factors), variation in chromosomal number or structure do arise in nature.

Chromosomal aberration may be grouped into two broad classes:
1. Structural 2. Numerical


Structural Chromosomal Aberrations

Chromosome structure variations result from chromosome breakage.
Broken chromosomes tend to re-join; if there is more than one break, rejoining occurs at random and not necessarily with the correct ends.

The result is structural changes in the chromosomes.

Chromosome breakage is caused by X-rays, various chemicals, and can also occur spontaneously.

There are four common type of structural aberrations:
1. Deletion or Deficiency
2. Duplication or Repeat
3. Inversion
4. Translocation.


Consider a normal chromosome with genes in alphabetical order: a b c d e f g h i

1. Deletion: part of the chromosome has been removed:
a b c g h i

2. Dupliction: part of the chromosome is duplicated:
a b c d e f d e f g h i

3. Inversion: part of the chromosome has been re-inserted in reverse order: a b c f e d g h i


4. translocation: parts of two non-homologous chromosomes are joined:
If one normal chromosome is a b c d e f g h i and the other chromosome is u v w x y z,
then a translocation between them would be
a b c d e f x y z and u v w g h i.





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