Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of bloom syndrome cells

Nathan Ellis, D. J. Lennon, M. Proytcheva, B. Alhadeff, E. E. Henderson, J. German

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Cells from persons with Bloom syndrome feature an elevated rate of sister- chromatid exchange (SCE). However, in some affected persons a minority of blood lymphocytes have a normal SCE rate. Persons who inherit the Bloom syndrome gene BLM identical by descent from a common ancestor very rarely exhibit this high SCE/low-SCE mosaicism; conversely, mosaicism arises predominantly in persons who do not share a common ancestor. These population data suggested that most persons with Bloom syndrome in whom the exceptional low-SCE cells arise are not homozygous for a mutation at BLM but instead are compound heterozygotes. Following this clue, we carried out a genotype analysis of loci syntenic with BLM in 11 persons who exhibited mosaicism. In five of them, polymorphic loci distal to BLM that were heterozygous in their high-SCE cells had become homozygous in their low-SCE cells, whereas heterozygous loci proximal to BLM remained heterozygous. These observations are interpreted to mean that intragenic recombination between paternally derived and maternally derived mutated sites within BLM can generate a functionally wild-type gene and that low-SCE lymphocytes are progeny of a somatic cell in which such intragenic recombination had occurred.

Original languageEnglish (US)
Pages (from-to)1019-1027
Number of pages9
JournalAmerican Journal of Human Genetics
Volume57
Issue number5
StatePublished - 1995
Externally publishedYes

Fingerprint

Bloom Syndrome
Sister Chromatid Exchange
Genetic Recombination
Phenotype
Mosaicism
Lymphocytes
Heterozygote
Genes
Genotype
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of bloom syndrome cells. / Ellis, Nathan; Lennon, D. J.; Proytcheva, M.; Alhadeff, B.; Henderson, E. E.; German, J.

In: American Journal of Human Genetics, Vol. 57, No. 5, 1995, p. 1019-1027.

Research output: Contribution to journalArticle

Ellis, Nathan ; Lennon, D. J. ; Proytcheva, M. ; Alhadeff, B. ; Henderson, E. E. ; German, J. / Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of bloom syndrome cells. In: American Journal of Human Genetics. 1995 ; Vol. 57, No. 5. pp. 1019-1027.
@article{4842bf8b8c3943a5ae7b2b47e32f92f6,
title = "Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of bloom syndrome cells",
abstract = "Cells from persons with Bloom syndrome feature an elevated rate of sister- chromatid exchange (SCE). However, in some affected persons a minority of blood lymphocytes have a normal SCE rate. Persons who inherit the Bloom syndrome gene BLM identical by descent from a common ancestor very rarely exhibit this high SCE/low-SCE mosaicism; conversely, mosaicism arises predominantly in persons who do not share a common ancestor. These population data suggested that most persons with Bloom syndrome in whom the exceptional low-SCE cells arise are not homozygous for a mutation at BLM but instead are compound heterozygotes. Following this clue, we carried out a genotype analysis of loci syntenic with BLM in 11 persons who exhibited mosaicism. In five of them, polymorphic loci distal to BLM that were heterozygous in their high-SCE cells had become homozygous in their low-SCE cells, whereas heterozygous loci proximal to BLM remained heterozygous. These observations are interpreted to mean that intragenic recombination between paternally derived and maternally derived mutated sites within BLM can generate a functionally wild-type gene and that low-SCE lymphocytes are progeny of a somatic cell in which such intragenic recombination had occurred.",
author = "Nathan Ellis and Lennon, {D. J.} and M. Proytcheva and B. Alhadeff and Henderson, {E. E.} and J. German",
year = "1995",
language = "English (US)",
volume = "57",
pages = "1019--1027",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of bloom syndrome cells

AU - Ellis, Nathan

AU - Lennon, D. J.

AU - Proytcheva, M.

AU - Alhadeff, B.

AU - Henderson, E. E.

AU - German, J.

PY - 1995

Y1 - 1995

N2 - Cells from persons with Bloom syndrome feature an elevated rate of sister- chromatid exchange (SCE). However, in some affected persons a minority of blood lymphocytes have a normal SCE rate. Persons who inherit the Bloom syndrome gene BLM identical by descent from a common ancestor very rarely exhibit this high SCE/low-SCE mosaicism; conversely, mosaicism arises predominantly in persons who do not share a common ancestor. These population data suggested that most persons with Bloom syndrome in whom the exceptional low-SCE cells arise are not homozygous for a mutation at BLM but instead are compound heterozygotes. Following this clue, we carried out a genotype analysis of loci syntenic with BLM in 11 persons who exhibited mosaicism. In five of them, polymorphic loci distal to BLM that were heterozygous in their high-SCE cells had become homozygous in their low-SCE cells, whereas heterozygous loci proximal to BLM remained heterozygous. These observations are interpreted to mean that intragenic recombination between paternally derived and maternally derived mutated sites within BLM can generate a functionally wild-type gene and that low-SCE lymphocytes are progeny of a somatic cell in which such intragenic recombination had occurred.

AB - Cells from persons with Bloom syndrome feature an elevated rate of sister- chromatid exchange (SCE). However, in some affected persons a minority of blood lymphocytes have a normal SCE rate. Persons who inherit the Bloom syndrome gene BLM identical by descent from a common ancestor very rarely exhibit this high SCE/low-SCE mosaicism; conversely, mosaicism arises predominantly in persons who do not share a common ancestor. These population data suggested that most persons with Bloom syndrome in whom the exceptional low-SCE cells arise are not homozygous for a mutation at BLM but instead are compound heterozygotes. Following this clue, we carried out a genotype analysis of loci syntenic with BLM in 11 persons who exhibited mosaicism. In five of them, polymorphic loci distal to BLM that were heterozygous in their high-SCE cells had become homozygous in their low-SCE cells, whereas heterozygous loci proximal to BLM remained heterozygous. These observations are interpreted to mean that intragenic recombination between paternally derived and maternally derived mutated sites within BLM can generate a functionally wild-type gene and that low-SCE lymphocytes are progeny of a somatic cell in which such intragenic recombination had occurred.

UR - http://www.scopus.com/inward/record.url?scp=0028859379&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028859379&partnerID=8YFLogxK

M3 - Article

C2 - 7485150

AN - SCOPUS:0028859379

VL - 57

SP - 1019

EP - 1027

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -