Genetics is central to biology. Underlying all life processes
is gene activity. DNA is made up of two chains.
Each chain consists of building blocks nucleotides. Within the nucleotides is deoxyribase, a
phosphate group and a base. The four bases
are adenine, guanine, cytosine and thyamine.
In RNA, uracil occurs in place of thiamine.
The sequence of
these bases within a strand determines the genetic information stored within
that strand. Ref: Peter J Russell. iGenetics 2nd edition. Pearson.
While a change in
the sequence of the gene may have no effect (known as polymorphism) there is
also a chance of a severe disruption of the function of certain genes. Ref:
geneticseducation.nhs.uk [accessed March 11th 2016]
Should gene
function be disrupted in this way, diseases can result These are known as mutations.
You can see below
in figure 1 the differences in functional and non functional protein.
Fig 1 – functional and non functional protein
Variations in a
DNA sequence depends on a number of factors
·
The
size of the variant
·
The
pathogenicity of the variant
Single nucleotide
polymorphisms (SNP’s) are common. This
is just one type of a variant. Rare genetic
conditions can be created but mutations are specific to only an individual
family. Ref: Peter J Russell. iGenetics 2nd edition. Pearson.
Depending on how
the error occurs determines if it is
·
Non –
disjunction
·
Segregation
errors
·
Translocation
errors
·
Recombination
errors
Segregation
errors have eggs or sperm which create too many or too few chromosomes. Fertilised eggs may have an extra chromosome
of a particular pair (trisomy). Monosomy is one chromosome fewer in each
cell. Turner syndrome and Klinefelter
syndrome can result from this.
Translocation
errors have no crossover occurring.
Often resulting in cancers forming.
Burkitt lymphoma affects chromosomes 8 and 14. Chronic myelogenous leukemia affects
chromosomes 9 and 22.
Recombination
errors involves the swapping of genetic materials between both chromosomes of
the same pair (homologous). Side by
side, they pair up, break, swap DNA and rejoin.
If the chromosomes realign and are misaligned, duplications can occur. Extra genetic material or deletions are
likely to occur which involves missing genetic material.
In non-homologous
pairs, the exchange gives chromosome translocations.
Reciprical
translocation involves the swapping of material.
Chromosomes can
also stick together end to end which is known as Robertsonian translocation.
Translocations
can lead to extra copies of genes causing over expression resulting in
disrupted cell function. Therefore, the
loss of generic material may lead to the cell missing copies of genes essential
to this activity.
Congenital
diseases occur when there are errors in Meiosis. While the list is endless and growing all the
time (some illnesses still are awaiting scientific evidence to confirm if they
are due to meiosis errors or not) many diseases are born from such errors.
Muscular
dystrophy is characterized by insufficient protein ‘dystrophin’ as you can see
below in figure 2.
Severe combined
immunodeficiency (SCID) is a heritable disorder where individuals have no
functional immune system. Minor infections
can cause death in such individuals at a very young age. The FDA approved the first human gene therapy
trial in 1990 on a girl called Ashanti DeSliva. She has an autosomal form of SCID
originating from mutation of the gene encoding adenosine deaminase (ADA) which
is an enzyme. Some white blood cells (T
cells) were isolated and mixed with a
retroviral vector
carrying an inserted copy of ADA. As the
virus infected many of the cells, a copy of the ADA gene was inserted into the
genome of some of the T cells.
Many treatments
of injection of these genetically altered T cells into Ashantis bloodstream and
she also periodically accepted injections of purified ADA protein.
More recently
SCID treatment has involved bone marrow stem cells being used (see fig 3 below)
with in vitro repopulation of the number of ADA producing cells. This gene therapy has been somewhat
successful in restoring health of a small number of children to date yet this
is still considered the most successful example of gene therapy. Ref: King,
Cummings, Spencer, Palladino Concepts of
Genetics Eleventh edition Pearson global [776-777]
Fig 3. Bone
marrow stem cell treatment in SCID ref: thriving.childrenshospital.org
There are many more similar autoimmune
illnesses such as crohns disease being researched to confirm or deny if a
chromosomal mutation is responsible for the illness.
Crohns disease is related to
chromosomes 5 and 10. Should an
individual have variations to the ATG16LI, IRGM and NOD2 increase the risk of
developing crohns disease. Also, the IL23R gene is associated with Crohns
disease. However, there is also an element that genetic and environmental
factors play a role in this disorder developing yet many of the causes still
remain unknown. Ref: Peter J
Russell. iGenetics 2nd edition.
Pearson.
Many diseases result from chromosomal
errors during meiosis. Huntingdons, muscular dystrophy, down syndrome, Turners
syndrome, Cri-du-chat syndrome, Burkitt lymphoma, Klinefelter syndrome and Cystic fibrosis are
examples.
glands, digestive tract and
reproductive system. Usually, the
epithelial cells release
slippery mucus to act as a lubricant,
trapping dust and bacteria.
However, cystic fibrosis makes
epithelial cells produce a protein. This
leads to thick sticky mucus which can block the bronchial tubes. Symptoms caused are coughing, tiredness,
fatigue and worse, often leading to the
need for organ transplants. The
digestive tract is also affected causing lack of nutrient absorbtion and bulky
stools. Ref: Peter J
Russell. iGenetics 2nd edition.
Pearson.
Tay-sachs disease has just one abnormal
chromosomal letter. Fatty materials in the brain should be dissolved under
normal conditions. However, with this
error, the proteins do not work. Fat
builds up, crushing critical brain cells.
Infants with this disease appear to develop normally for the first few
months of life. As nerve cells become
deposited with fatty particles the child becomes blind, deaf and unable to
swallow. Muscles also become atrophic.
Ref: Steve Parker, The concise human body
book, Dorling Kindersley
It is usual for the miracle of meiosis
to happen without errors. However, so many individuals suffer with diseases
caused by such errors. While this causes
sadness to all concerned and suffering, at what stage should medical
intervention stop?
In vitro fertilization (IVF) has shown
us that there is now technology to diagnose chromosomal abnormalities and
therefore decide which humans are allowed to go on and develop as babies.
Ethics dictate that this type of
diagnosis should perhaps not prevent scientists from allowing these illnesses
to be present in humans but rather develop ways to manage the illnesses.
Bibliography
Peter.J.Russell iGenetics A molecular approach. Second
Edition. Benjamin Cummings
Cystic Fibrosis,
Sams Story
Bozeman Science
“Mutations”
Arman Azad
“Causes – Crohns Disease”
Renan Mauch
“Cystic Fibrosis Pulmonary disease”
Shomus Biology
“Chromosomal Disorders”
AK lectures
“Chromosomal Deletion, inversion, duplication and translocation” “Aneuploidy
and non disjunction”
Kristen Kopronski
“Trisomy 21”
Steve Parker The Concise Human Body Book. Dorling
Kindersley
Voet, Voet and
Pratt Fundamentals of Biochemistry
upgrade edition – Wiley
Klug, Cummings,
Spencer, Palladino Concepts of genetics
eleventh edition Pearson
