The human genome - structural and functional - gave us the nature''s secrets of human life. Not only do we know about the genes that cause genetic defects but also those combinations of gene interactions that contribute to various late adulthood diseases like diabetes, high blood pressure, cardiac vascular and neurological diseases spectrum. It is also possible to scan the genes not only in adults in prenatal states but also in the embryo at a time when the development is less than even 100 hours.
Prospective couples can plan to assess the genes and get married to rule out genetic defects. Thus, gene scan contributes to the preventive medicine also. Unfortunately we do not realize that our endowment of genes inherently clashes with changing lifestyles contributing to the morbidity and mortality. The lifestyles of mankind have undergone enormous changes. Not only food habits have changed but also we are exposed to innumerable chemicals molecules that endanger genes. The food we eat, the water we drink and the air we breathe has become contaminated with chemicals that lead to life threatening situations. Thus it is all man made but not by nature.
Of late there has been an increasing awareness of the importance of genetic factors in health and disease. In other words genetic etiology has been implicated not only in genetic disorders but also in diseases of old age like diabetes mellitus, coronary artery disease and other neurogenic diseases.
The genetic morbidity and morality is quite considerable. As per the WHO estimates on global scale, 5% of children are born with hereditary disorders and almost 40% of adults are generally predisposed to common diseases during their lifetime. In the earlier years it was believed that the inherited genetic defects could not be treated. This seemingly nihilistic attitude has contributed to the stance by many doctors and behavioural scientists that genetics has little to contribute to their field. the discovery of inborn errors of metabolism by Dr. Garrod shows that such belief is erroneous. Our ability to influence the disease or behavioral abnormality depends on the depth of the insight with mechanisms.
When we analyze the genetic mutations contributing to the genetic morbidity or morality we find a clustering of these mutations in certain organs like vision, olfaction, (smell) audition (hearing) taste and touch, skin teeth and nervous system. An analysis of 1029 autosomal and 92 sex-linked mutations provided by DR. Mc. Cusick of john Hopkins University shows the clustering, as shown below:
| System | Autosomal | Sex - linked |
| 1. Nervous System | 8% | 15.2% |
| 2. Skeleton Connective tissue, internal organs blood groups Histocompatability | 33% | 1.3% |
| 3. Basic metabolism and endocrines | 36% | 31.5% |
| 4. Sense organs Vision, audition, olfaction touch, taste and Teeth | 23% | 37.0% |
Thus we find the higher fraction of nervous system and sense organs appear to be over represented on the human X chromosome, where as the genetic representation of body structure as well as basic metabolism is underrepresented.The human disease spectrum consists broadly three classes of diseases. Some solely determined by genes and others solely by pathogens and nutrition based and in between we find a class of diseases that are due to the interplay or interaction between genes and environment. Environmental factors that mainly influence the disease spectrum are the changing life styles, Innumerable mutagenic and carcinogenic molecules in the air we breathe, the water we drink and the food we eat.
The genetic disorders are solely determined by genes and chromosomal alterations. Chromosomes are the structures that carry the genes. These 24 in number and occur in pairs there are 23 pairs of chromosomes in each of the pair being inherited from the parents. 23 pairs are called autosomes and one pair is called sex chromosomes. The female has 22 pairs of autosomes and 2 X - chromosomes where as the males have 22 pairs of autosomes and one X chromosome and one Y chromosome. The sex is determined by the sex chromosomes. It is the male that determines the sex of the baby and not the female as often believed.
The genetic disorders stem from gene mutations and genome mutations (chromosomal). The chromosome number is fixed for each species and in human it is 23 pairs. Alterations do occur in chromosomes either in sets or in their structure. The change in sets in termed, as ploidy and the individual chromosomal variations (structural) are triosomy (3) or monosomy (one).
With regard to gene mutations that is gene based genetic disorders the number complied are about 5,000. Many have yet to be detected since of there are about 1,00,000 genes in humans. The effect of genome mutations like Down syndrome, Turners syndrome or Klinefelter syndrome are diagnosable at birth or even in prenatal period at 12 weeks pregnancy.
Chromosomal aberrations contribute to the extent of 15% in recognizable spontaneous.
The gene based are disease are either autotsomal or sex linked the most important genetic disorders most commonly seen in India are
* Duchenna muscular dystrophy
* Hemophilia A and B
* Lesoh - Nyhan syndrome
* Sickle call anemia
* The Taasemia
* Tay sach''s disease
* Polyposis
* Hyperparathyroidism
* Hypercholesterolaemia (high cholesterol leading to heart problems)
* About 200 enzyme defects that contribute to the abnormal metabolism or anemia''s
* Cataract
* Aniridia
* Hypertriglyceriadaemia (leading to cardiac problems)
* Huntington''s disease
* Chorea
* Gucoma
* Icthayosis
* ReEtinits pigmentosa
* Ataxia
* Mental retardation
* Deaf - mutism
* Xeroderma pigment o sum etc.
The disorders due to chromosomal changes are Down syndrome. Klinefelter and turner syndrome Down - translocation and mosaics to be brief.
The other group of diseases where there is an interplay between genes and environment are Common birth defects like neural tube defects cleft lip/palate, clubfoot/congenital heart disease.
Several of these genetic defects can be identified today by gene probes. Not only we identify the gene for causing a genetic defect but also predisposition to various diseases and susceptibility to other disease besides drug-induced reactions specific in certain individuals. There are three billion nucleotide pairs or chemical links. Forever 1,000 links there in a spot called single nucleotide polymorphyism (SNPs). One person may have A where as the other person has T. These SNPs that give everyone a unique genetic code except identical twins. Some SNPs matter more than others. Those SNPs that occur inside the genes the crucial segments of genetic code that endow people with physical characterists. SNPs in genes that affect how the body processes cholesterol. Those SNPs that fall outside the genes do clash with particular life style and contribute o various cardiovascular and neurogenic disorders.
(To be concluded)
The author is founder director (CRETD); Institute of Genetics Hospital for Genetics Diseases; Osmania University. Hyderabad (AP)
o various cardiovascular and neurogenic disorders.
(To be concluded)
The author is founder director (CRETD); Institute of Genetics Hospital for Genetics Diseases; Osmania University. Hyderabad (AP)