Single Gene Disorders
Monogenic or single-gene diseases are rare, with a prevalence of 0.004 to 0.005%. However, in India, the common practice of marriage within the community results in increased cases of rare diseases. India’s high genetic illness burden is directly proportional to the large population. The country reported 450 of the 5,000-8,000 uncommon genetic illnesses diagnosed worldwide. A 2018 News report revealed that 56 million individuals in the country suffer from single-gene disorders, also known as Mendelian disease.
Single-gene disorders occur due to mutations or variations of a specific gene that forms the DNA sequence. These disorders can have varying health consequences, ranging from mild to life-threatening conditions. Understanding how genes play a role in these diseases is essential for prudent family planning, early diagnosis, and effective management.
How Does Genetics Play A Role In Different Types Of Single Gene Disorders?
Different single-gene disorders cause different types of health abnormalities. Indian Heritage DNA genetic testing can identify specific mutations responsible for particular single-gene diseases, which can be categorized under the following four types based on their inheritance patterns:
These diseases happen in heterozygous states, meaning they occur even when only one of the two gene copies is mutated. So, even if a healthy gene is present, the mutated gene or allele overpowers it, causing the disease.
Autosomal dominant diseases are usually passed on through each generation, passing down from parents to their offspring with a 50% risk of development. Therefore, all children with a dominant mutant allele can be expected to develop the symptoms. A child can suffer severe disorder symptoms with two dominant mutant gene copies in case both parents are the carriers.
Some of the autosomal dominant diseases are:
- Huntington’s disease: A progressive neurodegenerative disease
- Marfan syndrome: Impacts the connective tissues supporting organs, muscles, tissues, and bones
- Neurofibromatosis: Noncancerous tumor development on the skin and in the nervous system
- Retinoblastoma: A type of eye cancer usually developing in the first five years of life
These diseases occur in homozygous states, meaning they occur if both gene copies are mutated. So, even if a mutated gene is present, the healthy allele overpowers it. Therefore, the disease only occurs when no healthy alleles are present, such as when a parent passes down two mutant alleles.
Autosomal recessive diseases can skip generations before the symptoms appear. The individuals may carry the mutant gene; however, there may be no disease due to the presence of a healthy gene.
Some of the autosomal recessive diseases are:
- Phenylketonuria: Affects the body’s ability to break down essential amino acid phenylalanine, which affects the brain and causes intellectual disabilities
- Cystic fibrosis: Affects sweat, mucus, and other fluid-producing cells, resulting in severe issues with respiratory and digestive system
- Sickle cell anemia: Affects the shape and elasticity of red blood cells, making it difficult to move across blood vessels and deliver oxygen
- Tay-Sachs disease: Results in fatty acid buildup, causing progressive deterioration of the brain and spinal cord.
These diseases occur when a mutant gene is present on the X chromosome. X-linked diseases are easier to find in the family tree because only women carry the X chromosome passed down by the father. So, an affected father may pass the illness to the daughter or make her a carrier.
Based on whether they occur in heterozygous or homozygous states, they’re further categorized as:
- X-linked recessive diseases
X-linked recessive diseases are more common in men than women because men only possess a single X chromosome, while females have two. When a mutation occurs on a male’s X chromosome, no healthy copy is available to restore normal function.
The illness often spreads from an “obligated” mother to son as she always receives the disease-causing gene from the father with this disorder. However, the carrier mother will not develop any symptoms.
Women have a 50% chance of inheriting the mutant gene from a carrier mother and becoming a carrier herself. A woman may have a possibility to develop the disorder if both parents are carrying mutated gene.
Some of the X-linked recessive diseases are:
- Red-green color blindness: Vision deficiency that causes individuals to view colors with red or green hues differently
- Haemophilia A: Causes deficiency of clotting factor, causing individuals to bleed easily and excessively
- Duchenne muscular dystrophy: A severe muscular dystrophy type that causes progressive degeneration of muscles
Glucose-6-phosphate dehydrogenase deficiency: Lack of enzyme G6PD that is necessary for red blood cells to function
X-linked dominant diseases
Males and females experience X-linked dominant disease at similar frequencies; however, only affected mothers can pass this disease to their sons. An affected father cannot pass X-linked dominant disease to his son as they don’t pass their X chromosome. Therefore, these diseases are more common in females than males.
Regardless. X-linked dominant disorders are rare.
Some of the X-linked dominant diseases are:
- Rett syndrome: Affects brain development, especially in females, causing progressive degeneration of motor and linguistic skills
- Inherited rickets: Causes weak bones in children
- Incontinentia pigmenti type 1: Growing skin abnormalities that evolve over the years
- X-linked lissencephaly and double-cortex syndrome: Impacts on neuronal migration while the embryo develops, which may cause distinct disorders in both sexes
Rare Y-linked disorders can only be handed down from males to their male offspring, as females don’t have the Y-chromosome.
Some of the X-linked dominant diseases are:
- Infertility issues in males: Caused by the absence of sperm in the semen
- Hypertrichosis of the ears: Causes excessive growth of hair on the outer helix of the ear
- Webbed toes: Causes joined skin between two or more toes
- Porcupine man disease: Presence of spiny scale-like lesions on the skin
Recognizing If You Have Single Gene
Disorders
Symptoms of single-gene disorders vary widely depending on the specific disorder but can include:
- Developmental delays
- Physical abnormalities
- Chronic illnesses
- Metabolic problems
Genetic predisposition affects the severity and progression of these symptoms. For instance, individuals with Cystic Fibrosis often experience severe respiratory and digestive issues from a young age.
Genetic testing is essential for diagnosing single-gene disorders or the presence of mutant genes in a carrier. It involves analyzing DNA to identify specific mutations responsible for the disorder.
Genetic insights from Indian Heritage DNA can enable personalized treatment plans. For example, individuals with genetic mutations causing metabolic disorders like Phenylketonuria (PKU) can make dietary adjustments to manage their condition effectively.
Genetic counseling and regular monitoring are crucial components of personalized care for those with single-gene disorders.
Plan Your Family’s Future With Indian Heritage DNA
FAQ'S
Genetic diseases from only one gene alteration are called single-gene or monogenic disorders. These conditions may develop when mutations change the structural proteins of the gene. Many families have a history of passing on single-gene illnesses to their children.
There are several single-gene disorders that are categorized based on their inheritance patterns:
- Autosomal Dominant
- Autosomal Recessive
- X-linked
- Y-linked
Single-gene disorders that are quite common around the world are cystic fibrosis, sickle cell anemia, hemochromatosis, and Tay-Sachs.