Haploinsufficiency

Haploinsufficiency is a term from genetics . Haploinsufficiency refers to a diploid (“double”) gene that cannot cause the normal phenotype in the haploid (“half”) state . Haploinsufficiency is an example of how the dominance of a disease- causing allele comes about.

Every diploid organism has two copies of a gene on its homologous chromosomes . When one copy has become inoperable due to an inherited mutation , and the one working copy of the gene does not produce a sufficient amount of the gene product (usually a protein), the hereditary disease occurs. A single mutated allele is therefore sufficient to develop the disease; heterozygous , i.e. mixed-breed carriers of the hereditary disease also fall ill .

For proteins that are present as oligomers in the organism, missense or nonsense mutations occur on an allele and can lead to inactive oligomers. The functionality of preserved alleles is thus dramatically reduced. One example is the tumor suppressor gene p53 , which (in addition to its importance for many tumors) is associated with Li-Fraumeni syndrome .

Mutants on one allele also favor the same mutation on the second allele through mitotic recombination or through copy choice in DNA replication. In addition to spontaneous mutations, these variants lead to a loss of heterozygosity and can lead to cancer . Examples include hereditary, bilateral retinoblastoma or familial adenomatous polyposis .

In contrast, with recessive inherited diseases, only homozygous , i.e. pure- inherited , gene carriers are affected .

Other examples of human hereditary diseases that are due to haploinsufficiency are:

• Chondrodysplasia
• Chorea huntington
• Polydactyly
• Marfan's Syndrome

literature

• Griffiths, Anthony J. et al .: Introduction to Genetic Analysis 8th Edition 2006, WH Freeman. ISBN 0-7167-4939-4
• Robinson P et al .: The molecular genetics of Marfan syndrome and related disorders . Journal of Medical Genetics (2006) 43: 769-787 PMID 16571647
• Eberhard Passarge, Jürgen Wirth: Pocket Atlas of Genetics . 2., completely revised and exp. Edition. Thieme, Stuttgart 2004, ISBN 3-13-759502-9 .