Monogenic disease

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A monogenic disease , also known as monogenic disease is designated, a disease caused by a defect in a single gene (= mono-gen ) is caused, so they "gene's disease A" is sometimes referred to as. Mostly these are inherited diseases . It is characteristic of monogenic diseases that they follow Mendelian rules in their inheritance pattern . They often appear in early childhood and in many cases have a serious chronic or even fatal course .

Since in principle all genes are susceptible to mutating from time to time , the number of different monogenic diseases is very large. The online database OMIM ( Online Mendelian Inheritance in Man ) recorded 2310 monogenic diseases as of June 2008, the genetic causes of which have been fully elucidated. In a further 1621 diseases, an inheritance pattern according to Mendel's rules could be demonstrated, but no knowledge was yet available about the molecular basis. In addition, a Mendelian inheritance pattern was assumed for a further 2084 phenotypic disease manifestations, so that the total number of confirmed or potentially monogenic diseases and phenotypes at this point in time was 6015. This contrasts with an estimate of the World Health Organization (for English. World Health Organization , WHO), according to the currently over 10,000 monogenic hereditary diseases with differentiable phenotype are known. While most of these diseases are extremely rare, taken together they are quite common. About one percent of newborns are affected. Here, however, just a handful of the most common single-gene diseases make up the lion's share: they represent almost half of all monogenic diseases occurring worldwide.

Since one and the same gene can be affected by different mutations , monogenetic diseases can also occur in different forms or manifestations. So today more than 500 mutations in and near for are phenylketonuria responsible PAH - gene known that the enzyme phenylalanine hydroxylase encoded. In the case of cystic fibrosis , 'monogenic' does not mean that there is only a single “disease allele ”: there are even more than 1000 allele variants in the gene that codes for CFTR (for Cystic Fibrosis Transmembrane Conductance Regulator ). These mutations are almost exclusively point mutations or deletions of between 1 and 84 base pairs . Even in the lysosomal storage disease Gaucher disease , more than 200 mutations in and near the GBA gene ( glucosylceramide β-glucosidase gene ) have been described to date . These examples are not special cases, but it appears that most, if not all monogenic diseases countless allelic variants have, we speak of thus, allelic heterogeneity '(Engl .: allelic heterogeneity ). Although referred to as monogenic , it is now known that some of these diseases are influenced by other genes, at least to a lesser extent. Other examples of diseases that are traced back to a single gene inherited Huntington's disease , severe combined immunodeficiency , muscular dystrophy or amyotrophic lateral sclerosis .

In July 2011, the steadily growing number of monogenic diseases diagnosable by means of DNA analysis was already well over 1,000, in comparison to this, a little more than 3,000 monogenic hereditary diseases are molecularly characterized today and could theoretically also be investigated using molecular biological methods.

Diseases that are caused by defects in several genes are called polygenetic diseases .

Allele variants that lead to different diseases are called allelic disease .

Individual evidence

  1. ↑ a b Hilke Stamatiadis-Smidt, Harald zur Hausen : The genome puzzle. Springer , Berlin 1998, ISBN 3-540-64326-5 , pp. 138f. limited preview in Google Book search
  2. ↑ a b Control of Hereditary Deseases, Report of a WHO Scientific Group (1996). (PDF; 4.8 MB) World Health Organization , accessed on May 6, 2010 .
  3. ^ Rare Genetic Disorders: Learning About Genetic Disease Through Gene Mapping, SNPs, and Microarray Data. Scitable by nature EDUCATION, accessed May 5, 2010 .
  4. ↑ Genomic resource center: Genetic Deseases. World Health Organization , accessed May 5, 2010 .
  5. ↑ a b D. W. Nebert et al: From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions . In: Drug Metab Rev . tape 40 , no. 2 , 2008, p. 187-224 , PMID 18464043 .
  6. ↑ Human Genetic Quality Network (HGQN) - A database of the BVDH ( see «Diseases»). Professional Association of German Human Geneticists V., accessed on July 15, 2011 .