INTRODUCTION

Even though we carry the same basic genetic material, we are all different. Even individuals with the same genetic disease may have very different presenting features, severity of disease, and clinical progression. What accounts for these differences? Some of our differences can be due to environmental influences, but others are caused by differences in our genes. The degree to which either genetics or the environment affects our external appearance forms the basis of the ‘nature and nurture’ debate. This chapter examines some of the reasons why individuals with the same genetic disease may differ from each other.

A person's phenotype is their external form (physical, physiological and biochemical), which may be within or outside normal boundaries. Their genotype refers to their underlying genetic make-up. The genotypephenotype correlation refers to the degree to which the genetic component influences the final physical form, and to what extent knowledge of the genotype might predict the phenotype. Heterogeneity is a term which indicates that something is ‘different in character’ or ‘varies in content’ (Oxford English Dictionary, 9th Edition). Phenotypes and genotypes are generally heterogeneous.

GENOTYPIC VARIATION

Different forms of a gene (alleles) exist in Hardy-Weinberg equilibrium in large randomly mating populations. However, certain alleles become more common in certain populations because several factors disturb this Hardy-Weinberg equilibrium. These factors include non-random mating, a rapid mutation rate, selection, a small population size, migration (gene flow between populations) and random drift.

Some of these factors may result in a disease-causing allele becoming common in a certain ethnic group, and the disease caused by this allele will then be more common in that ethnic group. It is important for medical professionals to be aware of the ethnicity of their patients for the following reasons: 1) certain diseases are more common in certain populations and therefore a high index of suspicion should be maintained in individuals with certain ethnic backgrounds, and 2) certain gene mutations are more common in certain population groups, and by providing a laboratory with information on the ethnic background of a patient, appropriate testing can be done, preventing a waste of time and money, and minimising the chance of obtaining false negative results.