Glossary

Variants of a gene. Every gene occupies a specific site on a chromosome, known as its gene locus. Alternative forms of the genetic information can occur at each locus – variants that developed in the past as a result of mutation. Each variant is termed an allele. From classical genetics we know, for example, that there are a number of alleles for flower color (red, white, etc.). Higher organisms have two copies of each chromosome (homologous chromosomes), except the sex chromosomes. By definition, homologous chromosomes always carry the same genes on corresponding sections. Those genes can be represented by either identical alleles (homozygosity) or non-identical alleles (heterozygosity).

A hereditary (genetic) disorder in which serum levels of alpha-1 antitrypsin are greatly reduced due to decreased production of the enzyme. This deficiency can lead to chronic diseases, which in adults mainly affect the lungs. In children the enzyme deficiency can cause liver damage.

The AlphaKit® is a system for applying and sending off blood drops – drawn for example from the fingertip. It consists of a piece of filter paper that is then saturated with blood. Once dry, it can be sent by normal mail to a special laboratory, where tests are performed to detect alpha-1 antitrypsin deficiency.

The building blocks of proteins. Around 20 amino acids occur in nature. Of these, the human body is able to synthesize only ten itself; the others must all be included in the diet. The various amino acids can link together in an infinite number of combinations to form protein molecules. The amino acid chains fold into specific three-dimensional structures. The function of a protein in the body is largely determined by how the amino acids combine and in what order they are linked. The structural plans for some proteins involve a combination of several gene segments. This is why there are more proteins than genes.

Chromosomes are long, thread-like structures in the cell nucleus. They consist of deoxyribonucleic acid (DNA), i.e. the genetic material, and proteins. Each animal and plant species has a characteristic number of chromosomes. The body cells of mammals contain two copies of each chromosome (diploid organism), except the X and Y sex chromosomes in males. One chromosome comes from the father, the other from the mother. The two match in terms of shape, structure and sequence of gene loci and are therefore described as homologous (matching). However, they are not identical, as different gene forms (alleles) can reside at corresponding gene loci.

The abbreviation COPD stands for chronic obstructive pulmonary disease. It does not refer to a unique disease entity but to a group of persistent (chronic) diseases of the lungs having similar symptoms. Doctors refer to COPD if one or more of the following pulmonary diseases is present:

• Chronic obstructive (= constricted) bronchitis)
• Abnormal hyperinflation of the lungs (pulmonary emphysema)

The main symptoms of COPD are: shortness of breath, cough and sputum production.

The chemical substance that carries genetic information. The building blocks of DNA (deoxyribonucleic acid) are nucleotides, which consist of a sugar (deoxyribose), a phosphate and a base. These building blocks link together to form an enormous molecule made up of two nucleotide strands in the form of a double helix.

ELISA (enzyme-linked immunosorbent assay) is a highly sensitive method for identifying certain molecules (proteins). It makes use of the mechanisms of the immune system. When the immune system recognizes a substance as foreign, it produces antibodies that attach to the foreign molecules, thus labeling it for destruction. ELISA exploits this process, known as the antibody-antigen reaction. Say a certain protein has to be identified and its antibody has been synthesized and is available. If the protein is present in a sample, the antibodies labelled with a colour substance and fixed on a carrier medium, will seek it out and dock to it. This triggers an enzyme-controlled reaction, resulting in a visible colored precipitate.

Pulmonary emphysema is due to chronic abnormal hyperinflation of the lungs and occurs predominantly in smokers. It can be caused by a genetic predisposition (alpha-1 antitrypsin deficiency) or chronic bronchitis, for example. Chronic or recurrent inflammatory processes lead to dilation of the air-filled structures in the lung tissue and damage to the lung structure. The unstable bronchi collapse, and the affected individual has trouble exhaling, as the inhaled air remains trapped in the resulting air cavities. In the course of time the lungs inflate more and more due to the trapped air, and the delicate walls separating the air sacs (alveoli) tear and sustain irreparable damage. The millions of elastic alveoli are replaced by few large cavities (sometimes several centimeters wide) from which air is unable to escape. The loss of alveoli leads to a considerable reduction in the surface area available for gas exchange in the lungs (absorption of oxygen and release of carbon dioxide).

Biocatalysts that facilitate and accelerate biochemical reactions. Enzymes are synthesized by all living cells and microorganisms. They work both inside and outside cells. Several tens of thousands of enzymes exist. They are highly specific in their action, i.e. each enzyme controls one type of biochemical reaction. The names of individual enzymes have the suffix  “ase”: an amylase splits starch, a chitinase chitin.

Significant worsening of the symptoms of a pre-existing chronic disease. If it develops suddenly, one speaks of an acute exacerbation.

Carriers of hereditary information on defined segments of DNA. A gene codes for a specific feature and resides at a specific site on a chromosome (the gene locus). A gene can occur in different variants (alleles). The expression of a trait may be controlled by several genes, or one gene may influence several traits. Humans have around 30,000 to 40,000 genes, all of which are present in every body cell. However, only those genes that are needed in a given cell are active.

The collective genetic information (residing on chromosomes) in a cell. The human genome contains 30,000 to 40,000 genes.

Genotype refers to all the genetic information encoded in DNA. It is distinguished from the phenotype (expressed traits) of an organism.

The body cells of all higher animals and many plants each contain two copies of chromosomes (diploid) – one from the father and the other from the mother. If a diploid organism has two different variants of a gene (alleles) for a given trait, it is said to be heterozygous for that trait. In such cases either one allele is expressed (i.e. it is dominant) or a mixed type results, for example in flower color, where a white allele and a red allele result in a pink flower.

The body cells of all higher animals and many plants each contain two copies of chromosomes (diploid) – one from the father and the other from the mother. If a diploid organism has identical genes for a specific trait on both (homologous) chromosomes, it is said to be homozygous for that trait.

These are the four variants (alleles) of the alpha-1 antitrypsin gene. M ist is the healthy allele, whereas S and Z are defective versions that can lead to alpha-1 antitrypsin deficiency. If the 0 allele is present, no alpha-1 antitrypsin is produced.

An undirected change in the genome. The change occurs at a more or less random site and affects a single gene. In some cases it has no effect, because the mutation occurs in an intron, a region of DNA that is not read. Mutations can occur spontaneously. However, they can also be artificially produced, for example by chemicals known as mutagens or by radioactivity.

An enzyme produced by neutrophil granulocytes (white blood cells) that is able to split peptide bonds (i.e. it is a protease). It is also able to digest elastin (a structural protein in the body) and plays a role in inflammatory processes. Neutrophil elastase is inactivated by alpha-1 antitrypsin.

A method by which minute amounts of a DNA segment can be copied in a chain reaction. The PCR method is used in many applications, for example in forensics to identify specific DNA sequences or establishing paternity and in medical diagnostic tests to identify viral DNA in the bloodstream.

The observable characteristics of an individual. The phenotype includes all internal and external structures and functions. The phenotype can change in the course of an individual’s development. Although the external characteristics of an organism are determined by its genetic information (genotype), the phenotype depends on which genes are actually expressed. Thus, sexually reproducing organisms possess many genes in two variants – one from the father and the other from the mother. Only the dominant gene is expressed.

Inhibits enzymes that split proteins (proteases), thus preventing the breakdown of proteins. Alpha-1 antitrypsin, for example, inactivates elastase in the lungs, thus preventing the lungs from self-destruction.

Molecules consisting of amino acids that play structural and functional roles in every living cell. They are responsible for the shape and structure of cells as well as for biochemical metabolic processes. They have manifold functions: There are, for example structural proteins (e.g. collagen), enzyme proteins, transport proteins (e.g. hemoglobin), immunoproteins and hormonal proteins. Humans have hundreds of thousands of different proteins constructed from just twenty amino acids. The sequence in which amino acids are linked together to form proteins is determined in the genetic code (DNA).