Genetic defects and diseases

There are over 4,000 separately identified genetic disorders and diseases which are a major contributing factor to human mortality and morbidity. The burden imposed upon the individual, the family, and society by genetic disease and genetically determined detrimental deviations from normal, although varying according to situation, is considerable. It is recognized today that between three and four percent of all individuals are born with genetic anomalies. One-third of these are attributable to gene-mutations, whose frequency is 1 per 1,000 individuals (per generation and per gene): the diseases in this group include haemophilia, albinism and various metabolic diseases (alkaptonuria, phenylketonuria, galactosemia, etc). Another third are due to chromosomal aberrations – one out of every hundred persons is born carrying an anomaly of this type. Trisomy 21 (Down's syndrome, formerly called mongolism) is the most frequent example. The rest are induced by untoward events during the intra-uterine life of the foetus such as X-rays or other forms of radiation, rubella (German measles) or certain other viruses, and chemical substances. The vast majority of the 'errors' caused by chromosome rearrangements or by gene mutations are of a non-beneficial character for the individual affected. Each category of genetic disease presents different problems with respect to causes, prevention, diagnosis and treatment. There are 3,000 to 4,000 human genetic diseases, 500 of them linked to a defect in a single gene. Many of the disorders are extremely rare, but they also include: cystic fibrosis, sickle-cell anaemia, haemophilia, and Tay-Sachs disease.

Genetic disorders can be either chromosomal or genic. Chromosomal disorders involve the lack, excess, or abnormal arrangement of chromosomes. Genic disorders are caused by either major mutant genes or by the interaction of many genes, each with a small effect. Environmental factors often cause modifications as well, and sometimes involve a developmental or physiological threshold. The origin of genetic disorders is mutation. Broadly defined, mutation refers to any stable change in the genetic material; it includes both numerical and structural chromosomal aberrations, such as extra or missing chromosomes, inversions, translocations, duplications, and deletions, as well as the whole range of single-gene alterations such as duplications, frame-shift insertions or deletions, inversions, and base-pair substitutions.

It has been estimated that 10% of all admissions to hospitals in industrialized countries are for genetic diseases. In the UK, about 15,000 children are born every year suffering from severe genetic physical and mental disease and genetic predispositions. Infants with defects are increasing at a rate of 12% per year and 40% of paediatric deaths in the UK are more or less directly related to genetic disease.