Can the genotype change spontaneously

Human genetics (preclinical)


The genetic information of an organism is stored and passed on in the form of nucleic acids (DNA or RNA). In higher organisms, the DNA is found divided between the chromosomes in the cell nucleus. Every organism has a characteristic number and shape of chromosomes: In humans there are 46 chromosomes in the body cells, 23 of which come from the father and 23 from the mother. These chromosomes can be divided into 22 pairs of autosomes and one pair of gonosomes.

Genetics describes the structure and function of the chromosomes as well as the rules of inheritance and explains the underlying molecular mechanisms. In particular, she deals with diseases, the cause of which lies in the change in genetic information. These genetic diseases occur in families, which is why analyzing family trees can be helpful in identifying them. In addition to the clinical examination, various laboratory methods are also available for diagnosis, e.g. to identify a mutation or chromosome change that is the basis of a disease. If a genetic disease is suspected and the genetic makeup of the parents is unknown, the risk of a child for a recessively inherited disease can at least be estimated using the Hardy-Weinberg law.

Basic concepts

To understand genetics, i.e. inheritance, mutations, hereditary diseases and the associated diagnostics, one should first make it clear at which level one is: At the level of individual molecules (e.g. DNA, bases, nucleotides, nucleosomes) or at the level of the chromosomes visible under a light microscope. Do you deal with the genetic basis of traits or their expression? Are you looking at an individual and their family or a whole population? These levels are of course all interconnected or at least provide explanations for observations on other levels.

Molecular level and chromosomes

  • Gen: basic unit of genetic information; Information-carrying section of DNA that is defined by its base sequence and usually codes for a protein
  • Gene locus: physical location of a gene on a chromosome
  • Allele: One of two or more possible DNA sequences that can occur at a specific gene locus. Typically, one allele is the “normal” (or wild-type allele) and occurs frequently, the other alleles are mutations (or polymorphisms) and occur less frequently.
    • Diploid cells either have the same allele on a gene locus (on each chromosome), in which case they are homozygous. Or they have two different alleles at this gene locus, in which case they are referred to as heterozygous.
    • Polymorphism: A rarer allele that occurs within a population but with a certain frequency
      • example
        • A population consists of 500 individuals with a diploid chromosome set.
        • All genes come in pairs, so there are a total of 1000 copies of each gene in this population.
        • There are two alleles for a particular gene, one of which is a polymorphism.
        • The allele frequency for this mutated gene is 1% = 0.01. This means that 10 of the total of 1000 copies of the gene carry the same mutation.
        • Assuming that the individuals with the polymorphism are heterozygous, that is, they each carry only one copy of the mutated gene, and the other is the “normal” variant of the gene, 10 individuals must have the polymorphism.
        • 10 individuals in a population of 500 individuals is 10/500 = 0.02 = 2%.

For the structure of DNA and chromosomes see also: Structure of DNA and RNA.

Characteristics, their genetic basis and their expression

  • Genotype: the entirety of the genetic makeup of an individual
    • The term genotype is often used when one means a certain set of alleles at one or more specific gene loci.
    • The phenotype develops from the genotype in interaction with the environment.
    • With regard to the genotype, a distinction is made between the following states:
      • Homozygosity: The two alleles at a certain gene locus are identical
      • Heterozygosity: The two alleles at a certain gene locus are different
      • Hemizygosity: There is only one allele of a gene in the genome. This is the case for genes located on the male's X or Y chromosome.
  • Phenotype: sum of all observable characteristics of an individual
    • The phenotype is determined by the combination of genotype and environmental factors. The characteristics include both the external appearance (e.g. eye or hair color) and the characteristics (e.g. behavior, character) of the individual.
    • A characteristic can be visible to different degrees in the phenotype.

Individual, family, population

  • Multiple allelia: There are more than two different alleles of a gene within a population
    • Occurrence: Likely to be found in all human genes
    • Example: AB0 blood group system
  • Basic terms related to genetic diseases:
    • Penetrance: The penetrance of a genetic disease indicates how likely it is actually to break out in a gene carrier.
    • Expressivity: The expressivity states how strongly a disease manifests itself in a gene carrier once it has broken out.
    • Compound heterozygosity: If the same gene is pathologically changed on both chromosomes, but in different ways (= different alleles), this can lead to a loss of function of the gene and thus to the occurrence of a recessive disease despite heterozygosity.
    • Anticipation: If a disease increases in severity over several generations or manifests itself earlier with each generation, this is called anticipation.


In meiosis, four daughter cells with recombined genetic material (mature sex cells, gametes) are created from one germ cell. This is the molecular biological basis for the inheritance rules, i.e. the estimation of the probabilities of how often certain alleles of a gene are passed on from the parents' generation to the children.

Mendelian rules

  • Requirements for the validity of Mendel's rules:

1. Mendel's rule (rule of uniformity)

  • Children (branch generation, F1 generation) of homozygous parents who differ in the observed characteristic are the same with regard to this characteristic, namely heterozygous.
    • Depending on how the inheritance takes place, the characteristic is different in the F1 generation:
      • Dominant recessive inheritance: All members of the F1 generation resemble the parent homozygous for the dominant allele.
      • Codominant inheritance: all members of the F1 generation look alike but are not like any parent.

1. Mendel's rule: The offspring of parents with different homozygous backgrounds are all uniformly heterozygous!

2. Mendel's rule (splitting rule)

2. Mendel's rule: The offspring of heterozygous parents are not uniform. The genotypes split in a ratio of 1: 2: 1!

3. Mendel's rule (rule of independence)

  • The inheritance of two or more characteristics takes place independently of one another and according to the first two Mendelian rules.
    • Prerequisite: independence of the possibility of combining alleles, either because they are on different chromosomes or so far apart on one chromosome that they are most likely separated by recombination.

3. Mendel's rule: Two or more characteristics are inherited (with certain restrictions) independently of one another!

Autosomal dominant inheritance

Important facts about autosomal dominant inheritance:

In the case of autosomal dominant diseases with complete penetrance, no generations are skipped!