A change in the genetic make-up (nucleotide sequence) of an organism is referred to as mutation. Mutations can cause changes in the structure of a protein; the expression of a protein may either be decreased or is completely lost. One should be well aware of the fact that functions of most of the mutations are unknown and result in polymorphisms, while some change the gene function to such an extent that a disease is manifested clinically. Mutations are largely categorized as dominant or recessive. On the other hand they could be either acquired or inherited. Mutations could predominantly be damaging to a cell or an organism as whole since any change in the sequence of DNA of an organism affects all the copies of the encoded protein. Thus it should be kept in view that mutations may or may not spawn changes in the phenotype of an organism.
A genetic disease is a disorder which marks the presence of abnormality in genes or chromosomes of an individual. Some of the genetic disorders ensue at the time of production of germ cells by parent (s), while others are a consequence of chromosomal abnormalities; to name a few are insertion, deletion, substitution or frame shift mutations. Genetic disorders are further classified as single gene disorders, polygenic disorders or mitochondrial disorders. Till date, around 4,000 genetic diseases have been discovered and the number is likely to increase with an advance in human molecular and medical genetics.
There is no recognized human population to which genetic disorders are not known. However, their nature, prevalence and distribution differ in various regions of the world. Nonetheless, Pakistan with a population size of over 125 million has managed to rise above the charts and is learned to be a goldmine of genetic disorders due to its unique geography and history; to mention a few are Down syndrome, Fragile X syndrome, Retinitis Pigmentosa, Gaucher disease, Congenital Cataract, Phenylketonurea, Deafness, Alopecias, Alzheimer’s, Albinism and Epilepsy. In addition to this Pakistan is an amalgam of various ethnicities with exceptional familial and social characteristics.
It is estimated that 700 children are born with genetic disabilities due to cousin marriages every year. Children born from first cousin marriages are at an elevated risk of miscarriage or infertility. According to another report in The Telegraph, the likelihood of unrelated couples baring genes causing recessive disorders is estimated to be 1 out of 100. On the other hand, the odds increase to as much as 1 in every 8 in case of cousin marriages.
In Pakistan, approximately 61.3 per cent of marriages are consanguineous while the ratio varies from 11 to 58 per cent in Muslim and neighbouring countries of Pakistan. It was acquired in another study conducted by two Indian doctors (Neurology Asia, 2012) that children of parents having blood relations had significantly higher rate of epilepsy, spontaneous abortion, intrauterine loss and stillbirth. It is approximated that the rate of children with Down’s syndrome exceeds 1.2-1.7 per 1000. In first cousin marriages, infant mortality rate is over 1.2 per cent. In terms of birth defects, the risk elevates from about 2 per cent in general population to 4-6 per cent when parents are related.
According to Statistics in Pakistan (PWD), the estimated population with genetic disorders is 29.2 million. Analysis shows that prevalence of such disorders is highest in Sindh with 3.05 per cent while lowest in Punjab (Islamabad) with a rate of 1.0 per cent. On the other hand according to another survey, rural areas are ahead urban areas with a percentage of 65.7 per cent and 34.3 per cent, respectively. It is estimated that 1.6 per 1000 are impaired with bilateral hearing loss in Pakistan amongst which 70 per cent of hearing loss tend to appear in consanguineous families.
It has been estimated that consanguineous couples and their offspring account for 10.4 per cent of the global population.
A strong family tradition of marrying in ‘beradari’ is giving rise to elevated percentage of consanguineous unions thus strengthening family bonds, conservation of family property and its structure, financial advantages because of no dowry, a closer and comparatively affectionate relation between the bride and her in-laws, comfort of marital provisions and elevated marriage stability of course are some of the reasons because of which the ratio of cousin marriages are greater in Pakistan. Consanguineous marriages are preferred because of lower domestic violence along with decreasing down the ratio of divorce. It would not be inappropriate to mention that illiteracy especially in rural areas also adds to the cause.
Majority of the population of Pakistan is not aware of the fact that consanguinity accompanies loss of fitness (biological) because of increase in genetic load specified to homozygosity. Therefore, it is acquired that consanguinity is one of the major cause of genetic disorders in Pakistan. According to report, ethnicity, religion, geography and language generate genetically isolated groups in which well-known, multigenerational pedigrees with a number of cases of rare disease are witnessed as stated by Dr Masood Akhter Sheikh, chairman of Pakistan Medical Society.
Furthermore, higher rate of birth, large family size and conception at old age are also some of the reasons of genetic disorders in Asian countries. There is a severe lack of public health awareness along with dearth of genetic counseling and health care before and during pregnancy. Therefore, there is a need to establish appropriate platforms for genetic counseling, genetic screening and pre-natal diagnosis.