VARIATION IN CHROMOSOME STRUCTURE

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INTRODUCTIONINTRODUCTION

Genetic variation refers to differences between members of the same species or those of different species◦Allelic variations are due to mutations in

particular genes◦Chromosomal aberrations are substantial

changes in chromosome structure or number.

Variation in Chromosome Variation in Chromosome StructureStructure

Cytogenetics -The field of genetics that involves the microscopic examination of chromosomes

A cytogeneticist typically examines the chromosomal composition of a particular cell or organism◦ This allows the detection of individuals with abnormal

chromosome number or structure◦ This also provides a way to distinguish between species

Since different chromosomes can be the same size and have the same centromere position, chromosomes are treated with stains to produce characteristic banding patterns Example: G-banding

Chromosomes are exposed to the dye Giemsa Some regions bind the dye heavily

Dark bands Some regions do not bind the stain well

Light bands

In humans 300 G bands are seen in metaphase 2,000 G bands in prophase

CytogeneticsCytogenetics

Cytogeneticists use three main features to identify and classify chromosomes 1. Location of the centromere 2. Size 3. Banding patterns

CytogeneticsCytogenetics

The banding pattern is useful in several ways:

1. It distinguishes Individual chromosomes from each other

2. It detects changes in chromosome structure 3. It reveals evolutionary relationships among

the chromosomes of closely-related species

CytogeneticsCytogenetics

There are two primary ways in which the structure of chromosomes can be altered 1. The total amount of genetic information in the

chromosome can change Deficiencies/Deletions Duplications

2. The genetic material remains the same, but is rearranged

Inversions Translocations

Mutations Can Alter Mutations Can Alter Chromosome StructureChromosome Structure

Deficiency (or deletion)◦ The loss of a chromosomal segment

Duplication◦ The repetition of a chromosomal segment compared to

the normal parent chromosomeInversion

◦ A change in the direction of part of the genetic material along a single chromosome

Translocation◦ A segment of one chromosome becomes attached to a

different chromosome◦ Simple translocations

One way transfer

◦ Reciprocal translocations Two way transfer

A chromosomal deficiency occurs when a chromosome breaks and a fragment is lost.

DeficienciesDeficiencies

The phenotypic consequences of deficiencies depends on the 1. Size of the deletion 2. Chromosomal material deleted

Causes Of Deletions* Heat or Radiation ( especially ionization)* Chemicals* Viruses* Errors in recombination

Deletions do not revert because the DNA is degraded.

DeficienciesDeficiencies

2 types:

terminal deletion or intercalary deletion.

single break near the end of the chromosome would be expected to result in terminal deficiency.

If two breaks occur, a section may be deleted and an intercalary deficiency created

example, the disease cri-du-chat syndrome in humans Caused by a deletion in the short arm of chromosome

The deletion results in several mental retardation and physical abnormalities , For Example ,Microcephaly

A chromosomal duplication is usually caused by abnormal events during recombination. And more than one copy present.

DuplicationsDuplications

Types DuplicationTypes Duplication-Tandem Duplicationsare adjacent to each other.-Reverse Tandem Duplicat-ions result in genes arrangedIn opposite order of theoriginal.-Tandem duplication at the end of chromosome is a Terminal tandem duplication .

Duplications can provide additional genes, Duplications can provide additional genes, forming gene familiesforming gene families

The genes in a duplicated region may accumulate mutations which alter their function◦ After many generations, they may have similar but distinct

functions◦ They are now members of a gene family◦ Two or more genes derived from a common ancestor are

homologous◦ Homologous genes within a single species are paralogs

Genes derived from a single ancestral gene

The globin genes all encode subunits of proteins that bind oxygen Over 500-600 million years, the ancestral globin gene

has been duplicated and altered so there are now 14 paralogs in this gene family on three different chromosomes

Different paralogs carry out similar but distinct functions All bind oxygen myoglobin stores oxygen in muscle cells different globins are in the red blood cells at different

developmental stages provide different characteristics corresponding to the oxygen

needs of the embryo, fetus and adult

A chromosomal inversion is a segment that has been flipped to the opposite orientation,

InversionsInversions

In an inversion, the total amount of genetic information stays the same

Therefore, the great majority of inversions have no phenotypic consequences

In rare cases, inversions can alter the phenotype of an individual

About 2% of the human population carries inversions that are detectable with a light microscope

Most of these individuals are phenotypically normal However, a few an produce offspring with genetic abnormalities

Individuals with one copy of a normal chromosome and one copy of an inverted chromosome

Inversion HeterozygotesInversion Heterozygotes

Such individuals may be phenotypically normal They also may have a high probability of producing gametes that are

abnormal in their genetic content The abnormality is due to crossing-over in the inverted segment

During meiosis I, homologous chromosomes synapse with each other

For the normal and inversion chromosome to synapse properly, an inversion loop must form

If a cross-over occurs within the inversion loop, highly abnormal chromosomes are produced

There are two main types of translocations ; *Reciprocal (balanced) translocations *Robertsonian(unbalanced) translocations

In reciprocal translocations two non-homologous chromosomes exchange genetic material.

Reciprocal translocations lead to a rearrangement of the genetic material, not a change in the total amount Thus, they are also called balanced translocations

TranslocationsTranslocations

In simple translocations the transfer of genetic material occurs in only one direction These are also called unbalanced translocations

Unbalanced translocations are associated with phenotypic abnormalities or even lethality

Example: Familial Down Syndrome In this condition, the majority of chromosome 21 is

attached to chromosome 14 The individual would have three copies of genes found

on a large segment of chromosome 21 Therefore, they exhibit the characteristics of Down syndrome

Familial Down Syndrome is an example of Robertsonian translocation

This translocation occurs as such Breaks occur at the extreme ends of the short arms of

two non-homologous acrocentric chromosomes The small acentric fragments are lost The larger fragments fuse at their centromeric regions to

form a single chromosome which is metacentric or submetacentric

This type of translocation is the most common type of chromosomal rearrangement in humans

Approximately one in 900 births