Back mutation can produce phenotype reversion in Bloom syndrome somatic cells Journal Article
| Authors: | Ellis, N. A.; Ciocci, S.; German, J. |
| Article Title: | Back mutation can produce phenotype reversion in Bloom syndrome somatic cells |
| Abstract: | A unique and constant feature of Bloom syndrome (BS) cells is an excessive rate of sister-chromatid exchange (SCE). However, in approximately 20% of persons with typical BS, mosaicism is observed in which a proportion of lymphocytes (usually a small one) exhibits a low-SCE rate. Persons with such mosaicism predominantly are genetic compounds for mutation at BLM, and the low-SCE lymphocytes are the progeny of a precursor cell in which intragenic recombination between the two sites of BLM mutation had generated a normal allele. Very exceptionally, however, persons with BS who exhibit mosaicism are homozygous for the causative mutation. In two such exceptional homozygous persons studied here, back mutation has been demonstrated: one person constitutionally was homozygous for the mutation 1544insA and the other for the mutation 2702G→A. Revertant (low-SCE) lymphoblastoid cells in each person were heterozygous for their mutations, i.e., a normal allele was now present. The normal alleles must have arisen by back mutation in a precursor cell, in one person by the deletion of an A base and, in the other, the nucleotide substitution of a G base for an A base. Thus, back mutation now becomes, together with intragenic recombination, an important genetic mechanism to consider when explaining examples of a reversion of somatic cells to "normal" in persons with a genetically determined abnormal phenotype. |
| Keywords: | clinical article; human cell; gene deletion; mutation; molecular genetics; phenotype; allele; somatic cell; heterozygote; stem cell; homozygosity; dna; heterozygosity; homozygote; sister chromatid exchange; dna sequence; lymphocyte count; mosaicism; lymphoblastoid cell; bloom syndrome; humans; human; male; female; priority journal; article; revertant |
| Journal Title: | Human Genetics |
| Volume: | 108 |
| Issue: | 2 |
| ISSN: | 0340-6717 |
| Publisher: | Springer |
| Date Published: | 2001-02-01 |
| Start Page: | 167 |
| End Page: | 173 |
| Language: | English |
| DOI: | 10.1007/s004390000447 |
| PUBMED: | 11281456 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Erratum/Corrigendum issued, see DOI: 10.1007/s004390100532 -- Export Date: 21 May 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work