Genetic variation is what makes us all unique, whether in terms of hair colour, skin

colour or even the shape of our faces.

Genetic variation is the difference in DNA sequences between individuals within a
population. Variation occurs in germ cells i.e. sperm and egg, and also in somatic (all
other) cells. Only variation that arises in germ cells can be inherited from one individual
to another and so affect population dynamics, and ultimately evolution. Mutations and
recombination are major sources of variation.

Mutations are the original source of genetic variation. A mutation is a permanent

alteration to a DNA sequence. De novo (new) mutations occur when there is an error
during DNA replication that is not corrected by DNA repair enzymes. It is only once the
error is copied by DNA replication, and fixed in the DNA that it is considered to be a
mutation (Figure 1). Mutations may be beneficial to the organism; deleterious (harmful)
to the organism; or neutral (have no effect on the fitness of the organism).

Variation

Individuals in a population are usually similar to each other, but not identical. Some of
this variation within a species is genetic, some is environmental, and some is a
combination of both.

Genetic causes of variation

Children usually look a little like both their mother and their father, but they will not be
identical to either one of them. This is because they get half of their inherited features
from each parent.
Each sperm cell and each egg cell contains half of the genetic information needed for
an individual (each one is haploid - it has half the normal number of chromosomes).
When these join at fertilisation, a new cell is formed. This zygote has all the genetic
information needed for an individual (it is diploid - it has the normal number of
chromosomes).
Examples of genetic variation in humans include blood group, skin colour and eye
colour.

Whether you have lobed or lobeless ears is due to genetic causes

Gender is also an inherited variation - whether you are male or female is a result of the
genes you inherited from your parents.

Environmental causes of variation

Characteristics of animal and plant species can be affected by factors such as climate,
diet, accidents, culture and lifestyle. For example, if you eat too much you will become
 heavier, and if you eat too little you will become lighter. A plant in the shade of a big tree
will grow taller to reach more light.
Other examples of features that show environmental variation include:
 language and religion
 flower colour in hydrangeas (these plants produce blue flowers in acidic soil and
pink flowers in alkaline soil)

It's useful to think of mutation as a process that creates genetic variation. We often refer
to a mutation as a thing—the genetic variation itself. This approach can be useful when
it comes to a gene associated with a disease: the disease allele carries a mutation, a
DNA change that compromises the protein's function. However, this approach gives
mutation a bad name.

It’s important to remember that losing the function of a gene doesn’t always affect
health. For example, most mammals have hundreds of genes that code for olfactory
receptors, proteins that help us smell. Losing one of these genes probably doesn’t make
all that much difference.

In contrast to variations that cause disease, there are many more examples of
variations that are neither good nor bad, but just different—like blood types and eye
color. Just like with disease alleles, the process of mutation creates these more neutral
variations. But with neutral variations, it can be impossible to tell which allele is the
"normal" one that existed first and which is the "mutant"—and the distinction is often
meaningless

Mutation

During replication, an organism’s genetic make-up (DNA) can change or mutate.

Changes to genes are called mutations. Mutations can be spontaneous (they just
happen). They can also happen because of:

Radiation
Chemicals, such as tar from cigarette smoke
If mutation is large then the organism will probably not survive to reproduce

If mutation is small then change might be beneficial. Offspring will flourish, doing better
than others in that species. Many more offspring will inherit this beneficial mutation and
will be better suited to that environment
Thus continues natural selection

Mutations may have no effect. For example, the protein that a mutated gene produces
may work just as well as the protein from the non-mutated gene.

Mutations may sometimes be helpful but they are often harmful. For example,
haemophilia is an inherited disorder that stops blood from clotting properly. It is caused
by a mutated gene.

Genes can be switched on and off. In any one cell, only some of the full set of available
genes are used. Different types of cells produce different ranges of proteins. This
affects the functions they can carry out. For example, only pancreas cells switch on the
gene for making the hormone insulin.

Mutations to genes can alter the production of certain proteins, or even prevent them
being made by a cell.

What is Pachyonychia Congenita?

Pachyonychia Congenita (PC) is a rare genetic disorder that primarily affects the skin, nails, and
mouth. It is caused by a mutation in any one of four genes that code for keratin proteins. Keratins
are proteins that form tough fibers that strengthen skin and things that grow out of the skin, such
as hair and finger nails. Although mutations in different keratins can cause many disorders, only
mutations in keratins 6a, 6b, 16, and 17 are linked to PC. This disorder does not affect lifespan,
but patients do experience constant pain.
Keratins are a family of related proteins with about 54 members. The keratin genes are located in two clusters, one
cluster on chromosome 12 and another on chromosome 17.

How do People Get PC?

PC has a predictable pattern of inheritance. People with PC have a 1 in 2 chance of passing the
disease to their children each time they conceive. In other words, the disorder exhibits an
autosomal dominant inheritance pattern. Children have to inherit just one copy of the mutated
keratin gene to exhibit symptoms.

In some cases, a person with PC will have no family history of the disease. This most commonly
happens when a mutation occurs very early in embryonic development, soon after fertilization. It
can also occur when a healthy parent's egg or sperm cells acquire a mutation in one of the keratin
genes. The mutated gene is passed to the child, resulting in disease. In most cases, the affected
child then has a 50% chance of passing PC to each of his or her children.

What is Adenosine deaminase (ADA) deficiency?

The disease is caused by a mutation in a gene on chromosome 20. The gene codes for the
enzyme adenosine deaminase (ADA). Without this enzyme, the body is unable to break down a
toxic substance called deoxyadenosine. The toxin builds up and destroys infection-fighting
immune cells called T and B lymphocytes.

ADA deficiency is one form of SCID (severe combined immunodeficiency), a disorder that affects the immune
system. ADA deficiency is very rare, but very dangerous, because a malfunctioning immune system leaves the body
open to infection from bacteria and viruses.
How do people get ADA deficiency?

ADA deficiency is an autosomal recessive disorder. Both parents need to pass a copy of the
defective gene to their child in order for that child to inherit the deficiency.

What are the symptoms of ADA deficiency?

Because ADA deficiency affects the immune system, people who have the disorder are more
susceptible to all kinds of infections, particularly those of the skin, respiratory system, and
gastrointestinal tract. They may also be shorter than normal. Sadly, most babies who are born
with the disorder die within a few months.
How do doctors diagnose ADA deficiency?

Doctors can identify ADA deficiency during the mother's pregnancy (1) by taking a tiny sample
of tissue from the amniotic sac where the baby develops (called chorionic villus sampling), or (2)
by looking at enzyme levels in a fetal blood sample taken from the umbilical cord. After the
child is born, doctors can test a sample of his or her blood to see if it contains ADA.

Sickle Cell
These are the sickle-shaped blood cells of someone with sickle cell anemia, a genetic disease common
among those of African descent.

Sickle cell anemia is the result of a point mutation, a change in just one nucleotide in the gene for
hemoglobin. This mutation causes the hemoglobin in red blood cells to distort to a sickle shape when
deoxygenated. The sickle-shaped blood cells clog in the capillaries, cutting off circulation.

Having two copies of the mutated genes cause sickle cell anemia, but having just one copy does not,
and can actually protect against malaria - an example of how mutations are sometimes beneficial.