Genetic Disorders in Man


The human DNA  is made up of 46 chromosomes, and each man has a definite sequence , and no two human being have the same gene makeup. This means that your genetic makeup is specific to you and this gives you your human capabilities, shape, intelligence,  weaknesses and strengths, susceptibility to illnesses, and immunity , amongst other things.
In the same way, any defect in your gene sequence, results in genetic disorders or illnesses. This would result in various manifestations of the abnormal gene formation in your DNA.
We all began life as a single cell at conception when an egg from your mum and sperm from your dad came together.  This single cell divided into two and then into four and so on until you developed into a complete human being made up of billions of cells.  It was your genes that instructed your cells to divide in this way and that controlled how you developed. The role your genes play in shaping who you are doesn’t end at birth.
Your genes are constantly being used by your body throughout your life to keep it functioning.  They interact with the environment around you and influence everything from your health to your appearance, your behaviour and your personality.
Inside almost every one of oure cells is a tiny structure called the nucleus which acts like the control centre of the cell.  Inside the nucleus are 46 chromosomes. Each one is made up of a long strand of DNA.  Along the length of the DNA strand are hundreds of genes (like beads on a piece of string – the string is the chromosome and the beads are the genes).
It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.

Our 46 chromosomes come in 23 pairs.  The chromosome pairs are numbered from the longest, number 1, to the shortest, number 22.  The 23rd pair of chromosomes are our sex chromosomes, the X and Y chromosomes.  Women have two X chromosomes (XX) and men have one X and one Y chromosome (XY).  All the other chromosomes are the same in males and females.
We inherit one chromosome in each pair from our mum and the other from our dad.

The strand of DNA which makes up each of your chromosomes is arranged into sections called genes.  Each gene is a single instruction which tells the body how to do a particular job
A genetic disorder is a genetic problem caused by one or more abnormalities in the genome, especially a condition that is present from birth (congenital). Most genetic disorders are quite rare and affect one person in every several thousands or millions.
Genetic disorders may be hereditary, passed down from the parents’ genes. In other genetic disorders, defects may be caused by new mutations or changes to the DNA. In such cases, the defect will only be passed down if it occurs in the germ line. The same disease, such as some forms of cancer, may be caused by an inherited genetic condition in some people, by new mutations in other people, and mainly by environmental causes in other people. Whether, when and to what extent a person with the genetic defect or abnormality will actually suffer from the disease is almost always affected by the environmental factors and events in the person’s development.
Some types of recessive gene disorders confer an advantage in certain environments when only one copy of the gene is present.

Genetic disorders can either be inherited from both parents or from a single parent. Genetic disorders can be caused by a mutation in one gene (monogenic disorder), by mutations in multiple genes (multifactorial inheritance disorder), by a combination of gene mutations and environmental factors, or by damage to chromosomes.
Monogenetic disorders are caused by a mutation in a single gene. The mutation may be present on one or both chromosomes (one chromosome inherited from each parent). Examples of monogenic disorders are: sickle cell disease, cystic fibrosis, polycystic kidney disease, and Tay-Sachs disease.
Genetic disorders can present as either Single gene or Multiple gene disorder.

Single gene disorders
A single-gene disorder is the result of a single mutated gene. Over 4000 human diseases are caused by single-gene defects.[4] Single-gene disorders can be passed on to subsequent generations in several ways.
Autosomal dominant-
Only one mutated copy of the gene will be necessary for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. The chance a child will inherit the mutated gene is 50%. Autosomal dominant conditions sometimes have reduced penetrance, which means although only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease.
Autosomal recessive-
Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% risk with each pregnancy of having a child affected by the disorder. Examples of this type of disorder are Albinism, sickle cell disease.

X-linked dominant
Main article: X-linked dominant
X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders have this inheritance pattern, with a prime example being X-linked rickets. Males and females are both affected in these disorders, with males typically being more severely affected than females. Some X-linked dominant conditions, are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen in females
X-linked recessive-
X-linked recessive conditions are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. A woman who is a carrier of an X-linked recessive disorder (XRXr) has a 50% chance of having sons who are affected and a 50% chance of having daughters who carry one copy of the mutated gene and are therefore carriers.

Y-linked disorders are caused by mutations on the Y chromosome. These conditions may only be transmitted from the heterogametic sex (e.g. male humans) to offspring of the same sex. More simply, this means that Y-linked disorders in humans can only be passed from men to their sons; females can never be affected.
Y-linked disorders are exceedingly rare but the most well-known examples typically cause infertility. Reproduction in such conditions is only possible through the circumvention of infertility by medical intervention.

This type of inheritance, also known as maternal inheritance, applies to genes encoded by mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only mothers can pass on mitochondrial DNA conditions to their children.

Multiple genes disorder
Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with the effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat, because the specific factors that cause most of these disorders have not yet been identified.
There is also a strong environmental component to many of them ,
• Asthma,  autoimmune diseases such as multiple sclerosis,    cancers
• Ciliopathies,  cleft palate, diabetes , blood pressure.
• heart disease,  hypertension ,   inflammatory bowel disease
• intellectual disability,  mood disorder,  obesity
• refractive error , infertility.
The most common genetic disorder in our own environment are sickle cell anemia, and Downs syndrome.

Downs syndrome
Down’s syndrome, also known as Down syndrome or trisomy 21, is a genetic condition that typically                causes some level of learning disability and certain physical characteristics.

Characteristics of Down’s syndrome
Most babies born with Down’s syndrome are diagnosed soon after birth and may have:
• floppiness (hypotonia)
• eyes that slant upwards and outwards
• a small mouth with a tongue that may stick out
• a flat back of the head
• below-average weight and length at birth
• their palm may have only one crease across it
Although children with Down’s syndrome share some common physical characteristics, they don’t all look the same. A child with Down’s will look more like their family members than other children who have the syndrome. People with Down’s syndrome will also have different personalities and abilities. Everyone born with Down’s syndrome will have some degree of learning disability, but this will be different for each person.

Causes of Down’s syndrome
Down’s syndrome is usually caused by an extra chromosome in a baby’s cells. In most cases, this isn’t inherited – it’s simply the result of a one-off genetic change in the sperm or egg. There’s a small chance of having a child with Down’s syndrome with any pregnancy, but the likelihood increases with the age of the mother. For example, a woman who is 20 has about a 1 in 1,500 chance of having a baby with Down’s, while a woman who is 40 has a 1 in 100 chance. There’s no evidence that anything done before or during pregnancy increases or decreases the chance of having a child with Down’s syndrome.

Tests for downs syndrome
• chorionic villus sampling (CVS) – a small sample of the placenta is tested, usually during weeks 11-14 of pregnancy
• amniocentesis – a sample of amniotic fluid is tested, usually during weeks 15-20 of pregnancy. If these tests show that your baby has Down’s syndrome, you and your baby’s other parent will be offered counselling so you can talk about the impact of the diagnosis.

Sickle cell anaemia
Sickle cell disease is the name for a group of inherited conditions that affect the red blood cells. The most serious type is called sickle cell anaemia.
Sickle cell disease mainly affects people of African, Caribbean, Middle Eastern, Eastern Mediterranean and Asian origin. People with sickle cell disease produce unusually shaped red blood cells that can cause problems because they don’t live as long as healthy blood cells and they can become stuck in blood vessels. Sickle cell disease is a serious and lifelong condition, although long-term treatment can help manage many of the problems associated with it.

Symptoms of sickle cell disease
People born with sickle cell disease sometimes experience problems from early childhood,  although most children have few symptoms and lead normal lives most of the time.
• painful episodes called sickle cell crises, which can be very severe and can last up to a week
• an increased risk of serious infections
• anaemia (where red blood cells can’t carry enough oxygen around the body), which can cause tiredness and shortness of breath
Some people also experience other problems such as delayed growth, strokes and lung problems.

Causes of sickle cell disease
Sickle cell disease is caused by a faulty gene that affects how red blood cells develop.
If both parents have this faulty gene, there’s a 25% chance of each child they have being born with sickle cell disease. The child’s parents often won’t have the condition themselves because they’re only carriers of the sickle cell trait.

Tests for sickle cell disease
Sickle cell disease is often detected during pregnancy or soon after birth.
Screening for sickle cell disease in pregnancy is offered to all pregnant women , to check if there’s a risk of a child being born with the condition, and all babies are offered screening as part of the newborn blood spot test (heel prick test).
Blood tests can also be carried out at any age to check for the condition or to see if you’re a carrier of the faulty gene that causes it.

Due to the wide range of genetic disorders that are presently known, diagnosis of a genetic disorder is widely varied and dependent of the disorder. Most genetic disorders are diagnosed at birth or during early childhood however some, such as Huntington’s disease, can escape detection until the patient is well into adulthood. The basic aspects of a  genetic disorder rests on the inheritance of genetic material. With an in depth family history, it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth, or contemplate termination. Prenatal diagnosis can detect the presence of characteristic abnormalities in fetal development through ultrasound, or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis.

Not all genetic disorders directly result in death; however, there are no known cures for genetic disorders. Many genetic disorders affect stages of development, such as Down syndrome, while others result in purely physical symptoms such as muscular dystrophy. Other disorders, such as Huntington’s disease, show no signs until adulthood. During the active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy. This includes physical therapy, pain management, and may include a selection of alternative medicine programs.

The treatment of genetic disorders is an ongoing battle with over 1800 gene therapy clinical trials having been completed, are ongoing, or have been approved worldwide. Despite this, most treatment options revolve around treating the symptoms of the disorders in an attempt to improve patient quality of life. Gene therapy refers to a form of treatment where a healthy gene is introduced to a patient. This should alleviate the defect caused by a faulty gene or slow the progression of disease.