Genetic disorder is a disease caused by a change in DNA sequence away from the normal sequence. The change can occur in whole or in part of the DNA sequence.

By Humaira Zeb

These changes can affect the individual bases (A, T, C, G) or much larger chunks of DNA or even chromosomes.  Genetic disorders can be caused by a mutation in one gene which can be known as monogenic disorder or by mutations in multiple genes that can be known as multifactorial disorder. As we unlock the secrets of the human genome, we are learning that nearly all diseases have a genetic component. Some diseases are caused by mutations that are inherited from the parents and are present in an individual at birth, like sickle cell disease. Others are caused by acquired mutations in a gene or group of genes that occur during a person’s life. Such mutations are not inherited from a parent, but occur either randomly or due to some environmental exposure (such as cigarette smoke). These include many cancers, as well as some forms of neurofibromatosis. Genetic disorder may cause rare diseases.

The term “rare disease” describes a group of diseases whose prevalence is so low that they are considered an unrealistic market for therapeutics in the absence of appropriate encouragements and support and too rare to be fully investigated and correctly managed by professionals. The rare genetic disorders frequently affect the nervous system with chronic, progressive, and degenerative pathology that excessively affects children. Rare diseases are defined by their prevalence rather than by unifying pathological or clinical characteristics. These diseases are infrequent; the reality is that ∼6,000 rare diseases collectively affect an estimated ∼300 million people worldwide.

As we know that nervous system is a highly complex organ that is responsible for performing different tasks such as receiving and processing sensory information and the control of highly compound behaviours that allow for survival. Neurodegenerative disorders occur due to weakening of neurons, leading to neurodegeneration and disabilities with the passage of time. Neurodegeneration is the progressive loss of structure and function of neurons form the Central or Peripheral nervous system CNS or PNS. Neurodevelopmental disorders contain the following conditions such as mental weakening, learning disabilities, hearing and visual impairment, cerebral palsy, autism spectrum, attention deficit hyperactivity disorders and neuromuscular disorder. Neurological diseases have a large number of causes including metabolic, viral, epileptogenic and environmental. Many of the neurogenetic disorder are caused due to consanguineous marriages and these consanguineous marriages are most frequently done in between first cousins. Cousin marriages are mostly done in Asian and Middle Eastern countries. The closer the biological relationship between the parents the greater is the chance that their offspring may be at higher risk to neurogenetical disorders because their offspring could get two identical copies of recessive genes from their parents. The consanguineous marriages have an effect on the rates of congenital malformation, reproductive loss and genetic diseases most commonly autosomal recessive.

Consanguinity is termed as wedlock or marriage between close blood relations or biological kin. Consanguineous marriages have been very common since the early existence of humanity. According to a rough estimate, nearly one billion (20%) of the global population live in communities with a preference for consanguineous marriages, predominantly in Muslim countries of the Middle East, Africa, and South Asia. With 65%, Pakistan has one of the highest rates of cousin marriages globally, followed by India (55%), Saudi Arabia (50%), Afghanistan (40%), Iran (30%), Egypt, and Turkey (20%).

Pakistan, a multi-cultural country with diverse caste systems, has been shown consistently the highest prevalence of consanguinity. Consanguineous marriages are encouraged in the country due to multiple reasons, e.g., to strengthen interfamily ties between close family members, a preference to the same caste and status, fear of incompatibility or difficulty in finding the right partner outside the family, security of being familiar with spouse and in-laws before marriage, restriction for socialization with the opposite gender, and financial limitations especially for dowry.

Countries all over the world have been working on the identification and prevalence of neurogenetical disorders. Pakistan is also one of those leading countries. Dr. Muhammad Ilyas, a young geneticist from Centre for Omic Sciences, Islamia College University Peshawar in collaboration with Department of Bioengineering, University of Engineering and Applied Sciences, Swat, NIBGE Faisalabad and University College London has initiated a project to explore the Genetic Architecture of Neurological Disorders in Pakhtun Population known as NeurOmics.

For this purpose, around 200 families have been identified in rural areas of KP, out of which, ~55 families have been studied and are being published in reputed journals. Whereas, the rest of the families are still in progress for the exome sequencing and functional analysis. Clinical screening of the patients is done with the help of neurologists in the local hospitals in Peshawar, Swat and Abbottabad. Characterization for the families in rural areas requires local research efforts. Once the genetic bases of these diseases are characterized, they are preventable. The NeurOmics project is precisely focused on the rural populations to address these issues.

The team has developed local training programs for public health and genomic research, including strengthening research capacity, training, and collaboration across the region. Their training program, establishment of new multidisciplinary research collaborations and the data and approaches they implement from this project will provide a national resource for Pakistani researchers, as well as facilitate genetic studies of all national ethnic populations.

Author :

Humaira Zeb

Research Scholar at the Centre for Omic Sciences, Peshawar