People who are sick look at those who are well and wonder: Why am I ill? Why not them? Is it the environmental pollution? Or my diet? Perhaps it is the witches, curses or the evil eye. Maybe incantations and amulets will set things right.
Human genes are located on 23 pairs of chromosomes
Today, rapid scientific advance in microbiology has helped identify disease-causing organisms (bacteria and viruses) not visible to the naked eye. Biochemistry has helped locate the exact molecular level at which enzyme reactions become faulty and result in diseases. We also know now that most diseases have a genetic basis. People may have the same genotype or genetic configuration, but the expression of these genes in the body (the phenotype) may be different. This makes one’s response to disease different from another’s — some succumb to it while others don’t.
Genes are located on specific loci on chromosomes. We inherit 20,000-30,000 genes, located on 23 pairs of chromosomes, from our parents. Twenty-two of these are identical. The 23rd is the sex chromosome. If it is expressed as XX, the person is a female and if it is XY, the person is a male.
Abnormal genes that theoretically should cause disease can vary in their penetrability. A person may carry the gene and yet not express the disease. But he or she will, however, pass it to his or her children. The disease may suddenly manifest itself generations later, puzzling everyone as to why no one in the family has it. This is true of vitiligo (white patches), icthyosis (dry skin), psoriasis and other conditions.
A single defective gene can produce abnormalities in multiple organs. The gene causing osteogenesis imperfecta (where the fragile bones keep breaking) also causes deafness and defective teeth. Some gene positive individuals may have normal bones, but their joints may be abnormally mobile and hyper extensible. They are often advertised in circus acts as “rubber or plastic people”.
A defective gene may be dominant — that is, it expresses itself in all the people who carry it. Or it may be recessive and a person expresses the disease only if he or she has inadvertently been saddled with two defective genes, one from each parent. This is most likely to occur in communities where consanguinity (marrying a relative like a cousin or an uncle) is prevalent. This accounts for diseases like sickle cell disease and thalassaemia.
Some traits are X-linked and carried on the X chromosome. Females are protected as they have two copies of the X, one from the mother and the other from the father. Males get their X from their mother and their Y from their father. Unprotected by a normal chromosome, they express any disease caused by a defective X from the mother. Muscular dystrophy and haemophilia are X-linked diseases carried by apparently normal women and passed on to their sons.
Sex limited inheritance may be expressed only in one sex even if the inheritance is dominant. A typical example is premature baldness. Men are more likely to be bald even though women, too, may carry the gene. Women are protected until menopause by the female hormones. Sometimes an abnormality occurs in a child despite the parents being genetically normal. This occurs because of spontaneous changes or mutations during early embryonic development, with an injury — like a viral infection, medications or radiation — causing the changes. Eighty per cent of “circus dwarfs” fall in this category.
As cells age, the proteins comprising genes become faulty. The chromosomes themselves may develop deletions, translocations and abnormal attachments. Parents may then give birth to children with diseases like Down’s Syndrome.
Many diseases like high blood pressure, diabetes, heart disease and cancer have a “multifactorial inheritance”. Although the defective genes have been inherited, the disease manifests itself only when there is the required mix of environmental and genetic factors. Alcoholism and drug abuse are hereditary, but will not manifest themselves in a regimentalised, teetotal society where neither alcohol nor drugs is available.
Genes, chromosomes and their inheritance can be plotted and studied. Genetic screening can identify people at risk for a particular disorder. Testing is appropriate even before symptoms begin if there is a strong family history of the disorder. In the case of sickle cell anaemia, thalassaemia and breast cancer, it may help to identify asymptomatic people and may be life saving. Tests can be done for some diseases before birth (in utero) with maternal blood samples, chorionic villous sampling, or amniotic fluid or umbilical cord blood. Neonates with inborn errors of metabolism (IEM) can be diagnosed a few hours after birth. At this time it may be possible to initiate life-saving treatment.
Gene therapy is being studied. It involves the insertion of copies of normal genes, switching off faulty genes or stem cell transplantation and therapy. Science is progressing by leaps and bounds. Perhaps the day is not far when genetic diseases, too, will be a part of the past.
Sources: The Telegraph (Kolkata, India)