How can a recessive allele be heterozygous

Glossary: ​​Technical terms in human genetics


Alternative forms of a gene that occur at corresponding gene loci on the homologous chromosomes. Within the population there are often many different alleles that can be classified as normal (so-called multiple alleles). The differences in the alleles are caused by sequence variations (polymorphism), which do not have to be important for the function of the corresponding gene product. As a rule, an individual inherits one allele of a gene from the mother and one from the father. If these alleles are identical, the individual is referred to as homozygous for this allele, if they are different as heterozygous.


Carrier of a mutation in an allele of a gene (= heterozygous). In these cases, the mutation in one allele is usually insufficient for the clinical manifestation of the disease. In the case of autosomal recessive inheritance, clinical manifestation only occurs when the second allele is also changed by a mutation.


If the disease manifests earlier and earlier in successive generations, one speaks of genetic anticipation.


Another word for it is "body chromosomes". There are chromosomes that are not involved in gender formation.


Chromosomes are the carriers of genetic information in the cell nucleus. They are carriers of many genes or alleles that are located at different gene loci on the chromosome. They consist of a long, continuous strand of DNA and proteins that is shaped like a double helix. If no nucleus division takes place, the chromosomes are in a relaxed, unspiralized state, as long strands of DNA. In order to be able to divide, the DNA strand in the cell nucleus must first double and connect to the newly created strand. The chromosomes are only visible under the microscope during the cell nucleus division, as the strands shorten by spiraling into a compact transport form. At the beginning of the nucleus division, the chromosomes consist of two identical strands of DNA that have spiraled into two "chromosome arms" (chromatids) (two-chromatid chromosome). The junction of the two chromatids is called the centromere. After successful nuclear division, the chromosomes again consist of only one chromatid / DNA strand (single chromatid chromosome) and then double again after a while.

Chromosomal aberration / chromosomal abnormality / chromosomal abnormality

A variation in the structure or number of chromosomes in a genome.

Contiguous gene syndromes

These are very small chromosomal malformations (mostly deletions or duplications) that are characterized by a specific complex appearance (phenotype). The causally affected DNA segment comprises several genes adjoining each other in a chromosome region, which independently contribute to the appearance.

Direct diagnostics

If the gene affected by a hereditary disease is known in terms of its location and nucleotide sequence (sequence of the chemical building blocks of DNA and RNA), the mutation in this gene can be identified directly in patients and carriers.

Disomy, uniparental

This means the presence of two homologous (identical) chromosomes or chromosome segments (partial disomy), both of which were inherited from one parent.


Lack of a chromosome or DNA segment. Interstitial deletion means loss of fragments within a chromosome in contrast to the terminal deletion, in which end sections of a chromosome are lost.

De novo deletion / de novo mutation

Deletion / mutation not inherited from one of the parents, but a new deletion / mutation in the affected individual.

DNA methylation

Term for the electrostatic attraction between two atoms (covalent bond) of a methyl radical to certain bases of the DNA. Methyl residues are the simplest atomic arrangement in organic chemistry, made up of carbon and hydrogen molecules. In human cells only cytosine residues (5-methyl-cytosine) are methylated in CG dinucleotides. DNA methylation has an important function in cells with a cell nucleus (eukaryotic cells) because it is involved in the organization of DNA structure and in the regulation of genes.

DNA replication

please refer Replication.

Dominant hereditary factor

Dominant means "dominating". A dominant hereditary factor in "mixed hereditary" (heterozygous) alleles prevails over a recessive hereditary factor in terms of trait expression. Recessive means "receding". So the allele just has to be present.


Two occurrences of the same chromosome segment or gene in the single (haploid) chromosome set.


Autosomal dominant inheritance

Mode of inheritance in which a trait is already pronounced if the triggering allele is only present once (heterozygous). The corresponding gene is on an autosome (not on a sex chromosome) and is inherited regardless of gender. The offspring of an affected person has a 50 percent risk of inheriting the triggering allele and also being a carrier of the trait.

Autosomal recessive inheritance

Mode of inheritance in which a trait only occurs if the triggering allele is present twice (= homozygosity). Heterozygous gene carriers (allele only present) are usually not recognizable clinically; they are referred to as carriers. The corresponding gene is located on an autosome and is inherited regardless of gender. In the case of heterozygous, clinically healthy parents, there is a risk of 25 percent for an affected child.

X-linked recessive inheritance

Inheritance in which the causative gene is located on the X chromosome and in men (hemizygous) leads to the expression of traits. Women are only carriers of traits if they have inherited the triggering allele twice (homozygous). Heterozygous (single allele) affected women usually show no clinical symptoms, but are carriers of the trait and have a 50 percent risk for affected sons and daughters, who in turn are carriers.

X-linked dominant inheritance

Inheritance in which the gene is located on the X chromosome and the corresponding characteristic is expressed in the presence of only one triggering allele. In contrast to the X-linked recessive inheritance, in addition to hemizygous men (the allele is on the X chromosome, which occurs only once in the otherwise double set of chromosomes), heterozygous women are also affected, in whom the allele is simply present.


DNA segment of a eukaryotic gene (forms cells with a cell nucleus) that carries information for the corresponding protein. The non-coding DNA segments, the so-called introns, are located between the exons of a gene.


please refer Gene expression.


Type and extent of the phenotypic expression (appearance) of a penetrant gene (see also Penetrance).

Fluorescence In Situ Hybridization (FISH)

Molecular cytogenetic method for the detection of chromosomal rearrangements, (micro) deletions, chromosomal localization or the number of copies of a gene. In the first step, biotinylated nucleotides (DNA building blocks that have combined with a certain vitamin) are incorporated into specific DNA probes. Specific DNA probes are short, single-stranded DNA fragments that are used to detect complementary DNA or RNA sequences. After subsequent hybridization of metaphase cells with these probes, they are made visible with fluorescein isothiocyanate-labeled avidin, a special protein. The number and location of the detectable fluorescent points corresponds to the number of gene copies (usually 2) and their chromosomal location.

Gel electrophoresis

DNA molecules carry negative charges, which enables the molecules to move in the electric field. If this movement takes place within a suitable matrix (agarose or polyacrylamide), DNA molecules migrate according to their molecular weight and can be separated according to their size.

Gene dose

All autosomal genes, i.e. all genes that are not involved in gender development, are present in duplicate in the genome. Many genes must also be expressed from both alleles in order to maintain normal cell function. Is z. For example, if an allele of a gene has been lost, half the gene dose may not be sufficient for normal cell function.

Gene expression

Term for all processes in which a copy in the form of RNA (messenger RNA) is made from the nucleotide sequence of a gene by transcription and then the corresponding protein (gene product) is synthesized by translation.

Gene locus, locus

Physical position at which an allele is on a chromosome.

Haplotype analysis

In the haplotype analysis, so-called polymorphic DNA markers can be used to track the inheritance of a chromosomal area within a family. Even if the exact location and sequence of the gene that causes the disease is unknown within this range, knowledge of the inheritance of the chromosome region can indirectly indicate the inheritance of the mutation. An unknown mutation can also be detected indirectly in a known gene. This procedure is chosen if the direct search for mutations in the corresponding gene is too time-consuming. The haplotype analysis is a family examination. It is therefore necessary that as many family members as possible take part in addition to the person affected.


Heterologous means "different" or "different". It's the opposite of homologous. Heterologous means that the chromosomes of a chromosome pair from a diploid chromosome set (a maternal and a paternal chromosome) differ from one another.


Homolog means "similar". Homologous pairs of chromosomes mean that every chromosome in a human cell is present in duplicate (a maternal and a paternal chromosome).

Imprinting, genomic

An imprinting of certain genes that takes place in the early embryonic development, depending on whether they are of maternal or paternal origin. Depending on the parental origin of the genes, imprinting causes their gene activity to differ, i. H. a few genes are only active on the chromosomes inherited from the mother, other genes only on the chromosomes inherited from the father. At the biochemical level, imprinting is probably based on methylation of DNA.

Imprinting mutation

In some clinical pictures, reduced or increased methylation of the DNA can be detected, which is presumably the cause of the disease. The mutations that lead to disturbed methylation are known as imprinting mutations.

Indirect diagnostics

If the chromosomal position of a gene affected by a genetic disease is known, but the gene itself has not yet been isolated, or if a known gene is so large that not every mutation can be detected directly, a genetic defect can be diagnosed indirectly. Please referHaplotype analysis.

Index patient

At z. B. autosomal dominant inheritance, the molecular genetic examination of a hereditary condition is initially only carried out in one affected family member (= index patient), since the disease is very likely to be caused by the same mutation in the other affected family members. Only after identifying the mutation causing the disease in the index patient are the other family members specifically examined for this mutation.


Non-information-carrying DNA section of a eukaryotic gene (forms cells with a cell nucleus) that is located between exons.


Chromosome set of an individual, which is defined both by the number of chromosomes and by their microscopic shape and structure in the mitotic metaphase (phase of cell nucleus division = mitosis).


Pairwise arrangement of the homologous chromosomes according to length, position of the centromere (constriction cell) and according to the pattern of the chromosome bands for systematic analysis of the chromosomes.

Germline mutation

A mutation that originated in the germline (egg or sperm) of one of the parents. If it is passed on to a child (50 percent probability), it can be detected in all of the child's cells (again also in cells of the germ line).


z. B. Hemophilia A: If a woman carries a mutation in an allele of the factor VIII gene (= heterozygous), she is not clinically affected by the disease. However, it is the carrier or carrier for the disease because it has a 50 percent risk for affected male offspring and for daughters with carrier characteristics.


Small deletion (<2Mb), which is usually not cytogenetically recognizable, which can be detected by means of FISH or other molecular genetic methods.

Mismatch repair

In DNA replication (see:Replication) resulting errors such as B. Incorrect base pairings (= mismatch) are corrected in the cell nucleus by an enzyme complex.


Diseases caused by mutations in a certain gene are called monogenic hereditary diseases. About 6000 such diseases have been described so far.


Monosomy means the absence of one or more individual chromosomes in an otherwise diploid set of chromosomes (each containing two homologous chromosomes). In interstitial monosomy, only a fragment within a chromosome is missing.


Missense mutation

The base exchange at a position in the DNA sequence can lead to the incorporation of the wrong amino acid in the corresponding protein.

New mutation

New mutation after fertilization of the egg. Depending on the point in time of occurrence in development, a distinction is essentially made between two cases: If the occurrence is very early, almost all cells of the developing individual are affected, possibly including the cells of the germ line, as a rule, full clinical manifestation occurs. If it occurs later, only the cells of certain tissues are affected; this is called a somatic mutation with a mosaic for certain tissues. Clinically, all variations from severely to not affected are possible.

Nonsense mutation

In protein biosynthesis (expression; production of a protein in a living being), termination takes place through so-called stop codons (three-part base combination), which are recognized as such by the protein synthesis apparatus. If a new stop codon is generated as a result of a mutation in the coding region of a gene, the protein synthesis is prematurely terminated. The result is a shortened, possibly functionless protein.

Point mutation

Change at one point in the DNA sequence, e.g. B. Exchange of a nucleotide (DNA building block). This term also includes changes that are caused by deletion or insertion (incorporation) of one or more base pairs.

Splice site mutation

The coding exon sequences of a gene must be assembled at the level of the RNA; H. the intron sequences must be removed. This process is called "splicing". The splice apparatus recognizes the beginning and the end of an exon, the so-called exon-intron boundary, by the base sequence in this area. If an essential base of this recognition sequence is exchanged, the corresponding exon is not taken into account during the splicing process, which leads to the synthesis of an altered protein.

Triplet repeat extension, dynamic mutation

Successive identical nucleotide triplets occur in different areas in the human genome. The number of such nucleotide triplets (triplet repeats, triplet repeats) at a gene locus is variable in the general population, but limited to a certain normal range and shows only minor changes within a family over generations. A previously unknown mechanism can lead to an increase in the number of triplet repetitions above a critical threshold value. If this too large number of nucleotide triplets (triplet repeat extension) is present in the range of genes, it can cause diseases. The effects of the increased number of triplet repetitions are different, usually they cause a decreased synthesis or a dysfunction of the corresponding protein. A special feature of this mutation mechanism is its dynamics: once the number of triplet repetitions has exceeded the critical value, it can increase from generation to generation (dynamic mutation). Since the severity and age of manifestation of the diseases are related to the number of triplet repetitions, the phenomenon of genetic anticipation (see above) can be explained in this way.


Basic building block of DNA and RNA. It is a molecule with a phosphate, a sugar and a base component.

Nucleotide triplet

Sequence of three nucleotides (e.g. CAG).

PCR, polymerase chain reaction

Method for in vitro amplification (reproduction of DNA sections) of a specific DNA sequence with the help of DNA polymerases (enzyme for the synthesis of DNA). The amplification takes place by cyclically repeated addition of single-stranded, synthetically produced DNA fragments (primers) to denatured (single-stranded) genomic DNA and extension of these fragments by a DNA polymerase. The DNA sequences to which the primers attach must be known.


Frequency in percent with which a gene or a mutation in a gene manifests itself in the phenotype.


Occurrence of two or more different genotypes in a population. The different genotypes can be traced back to DNA sequence variations, which are found to a certain percentage in the population and have no pathogenetic correlate.


In eukaryotic genes (cells with a cell nucleus), a DNA region approx. 100 bp long before the start of transcription of a gene, from which the transcription of the gene is controlled. In this area there are recognition sequences for the enzyme complex of transcription and for regulatory proteins.


Before each cell division, the set of chromosomes must be duplicated in order to ensure that all genetic material is passed on to the daughter cells. This happens through DNA replication, in which specific enzymes lead to an identical duplication of the DNA molecules in the cell.

Restriction enzymes

DNA endonucleases that bind to specific nucleotide sequences on the DNA and cut the DNA strand at this point.


Recessive means "receding". Hereditary factors in "mixed hereditary" (heterozygous) alleles are recessive if they do not appear in the characteristic expression compared to a dominant hereditary factor. In order for the recessive factor to prevail, it must be "homozygous"; H. it must be inherited from both parents. The hereditary factor must therefore be present twice.

Sequence analysis, sequencing

Automated methods for analyzing the nucleotide sequence of DNA fragments.

Sequence gel electrophoresis

Special form of gel electrophoresis for analyzing the nucleotide sequence of DNA fragments. Here, very short, single-stranded DNA fragments (denatured DNA strands) are separated and detected in a polyacrylamide gel according to their length and nucleotide sequence.

Somatic mutation

If a mutation occurs after an egg cell has been fertilized, not all tissues of the resulting individual are usually affected by this mutation. By definition, the cells of the germline are not affected by the mutation.

Southern blot hybridization

A technique to detect specific DNA fragments and analyze their size. For this purpose, genomic DNA is usually split into fragments with restriction enzymes, which are separated according to size by means of gel electrophoresis and then transferred to a membrane (Southern blot). This membrane is then incubated with a specific, radioactively labeled DNA probe. If the complementary DNA sequence is present on the membrane, the probe attaches to this sequence (hybridization) and can then be detected with an autoradiography.

SSCP analysis, single-stranded conformation polymorphism analysis

Single-stranded conformational polymorphism analysis: screening method for mutations that is based on the different electrophoretic behavior of single-stranded DNAs with minimally different nucleotide sequences. For this examination, the affected area of ​​DNA (mostly individual exons of genes that are mutated in certain diseases) is first amplified using PCR. After the multiplication, the double-stranded PCR products are denatured in order to obtain single strands, which are then examined for their running behavior in gel electrophoresis. A difference of a single nucleotide leads to a changed conformation of the single strand and to a changed running behavior in the gel.


First step in the expression of genes. A messenger RNA copy of an information-carrying DNA segment (gene) is synthesized in the cell nucleus by means of an RNA polymerase enzyme complex. Translation then takes place in the cytosol of the cell.


Second step in the expression of genes. The information transferred to messenger RNA during transcription is read on the ribosomal protein synthesis apparatus and translated into the corresponding amino acid sequence.


Chromosomal structure change through rearrangement of a chromosome segment, e.g. B. Loss, replacement or displacement of individual chromosome pieces.

Trinucleotide repeat, triplet repeat

Repetitions of a DNA sequence that occur several times in a row, each consisting of three nucleotides (e.g. CAG).


please refer Inheritance.

X inactivation

Inactivation of one of the two X chromosomes in somatic cells of female organisms during the early embryonic period (Lyon hypothesis). Originally paternal or maternal X chromosomes are randomly inactivated (random X inactivation).