Every human being has a unique genome with variations in an enormously large number of gene loci and this means nothing else than all human beings differ from each other in a huge number of individual bases on their chromosomes. One also terms such punctual differences of the base sequence "SNPs" or "single nucleotide polymorphism". How SNPs and diseases are connected has still been too rarely investigated.
If a genetically determined characteristic does not fit in with the simple Mendel's inheritance laws and, in addition, is variably expressed, one can assume that either several genes take part in the expression of the characteristic (--> polygeny) or a genetic disposition is present that, in an interplay with partially unknown factors, is also responsible for it (--> multifactorial inheritance).
If it is only environmental factors that have influence on the phenotype in the same genotype, one speaks of flowing modifications.
Furthermore it must be taken into account that some diseases and abnormalities do not occur equally frequently or with the same intensity in both sexes. Probably the genetic disposition or genomic imprinting plays an important role thereby.
SNPs or single nucleotide polymorphism
Not every mutation of the base sequence means a pathogenic alteration of the genome. There are the single nucleotide polymorphisms (SNPs) or single letter variations in the DNA sequence. Today SNP maps exist in which all currently known polymorphisms are stored and are available for scientists to use. One knows between 1.42 and 2.1 million SNPs. They occur on average with a frequency of 1 SNP per 1910 bases with regional differences. The least SNPs happen to the X chromosome and, in general, SNPs occur more often in the intron DNA segments as in the exon segments that contain information regarding the AS sequence of the proteins. The SNPs represent very individual information with whose help, today, the genetic "fingerprinting" for paternity cases or in forensics are performed.
A more exact study of SNPs is also very interesting from the point of view of diseases that are complex and are probably based on combined changes to various genes (polygeny).
Combinations of SNPs are known that make certain diseases more likely or, in the best case, improve resistance to certain illnesses.
Polygenic and multifactorial hereditary disease
Today one knows diseases that are caused by the combined effects of various genes. Such illnesses are most often due to polygeny or multifactorial inheritance. If a predisposition (due to genetic and environmental factors) is known, prophylactic measures can possibly be undertaken against it. The search for underlying, predisposing genetic variations as well as the number and kind of the environmental factors that are involved is very difficult, however, since such diseases do not obey the simple mendelian laws.
The following example should show a disease that, on the one hand, is caused polygenically and, on the other hand, is influenced by environmental factors. In epidemiological studies the incidence for gene variants that are responsible for this disease were determined in a population of patients with this illness.
In examining individual families that have been affected, it can happen that distribution patterns of the various gene variants are found that are totally different than in the general population (compare the multifactorial inheritance figure). This shows that in many complex diseases predisposing polygenic factors must indeed be present. These factors alone are not enough, though, to explain the disease or abnormality sufficiently well. In individual families environmental factors and differences in lifestyle must also be involved that cannot be known in detail.
Finally, one must mention that the proportion of the genes and environmental factors change in how they influence a symptom and this can only be investigated through twin and adoption studies. It is indeed true that the genes that are involved are inherited in accordance with Mendel's laws, but how the symptoms are expressed and the appearance of the disease/abnormality is the sum of the individual genes. This is also termed an additive gene effect. In certain symptoms, though, the additive gene effect for their expression must exceed a threshold, whereby the individual gene variations correspond to the normal distribution in the general population. One also calls such mutual influencing of two genes with different gene locations epistasis.