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Bloom's syndrome. XIX. Cytogenetic and population evidence for genetic heterogeneity
Author(s) -
German James,
Ellis Nathan A.,
Proytcheva Maria
Publication year - 1996
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1996.tb03778.x
Subject(s) - genetics , bloom syndrome , biology , sister chromatid exchange , locus (genetics) , population , loss of heterozygosity , most recent common ancestor , allele , phenotype , ancestor , gene , demography , dna , phylogenetics , helicase , history , rna , archaeology , sociology
Cells with abnormally high rates of sister‐chromatid exchange (SCE) are uniquely characteristic of Bloom's syndrome (BS). However, in one in five persons a minor population of cells with a low‐SCE phenotype circulates in the blood. The origin and significance of the low‐SCE cells in BS have never been understood, although they are assumed to arise by somatic mutation. In the present investigation, the enigmatic high‐SCE/low‐SCE mosaicism was investigated by comparing the incidence in several subpopulations of persons in the Bloom's Syndrome Registry who exhibit the two types of cells, and a striking negative correlation emerged: in persons with BS whose parents share a common ancestor, the case in approximately half of registered persons, low‐SCE cells are found only rarely; conversely, the mosaicism occurs almost exclusively in persons with BS whose parents are not known to share a common ancestor. Because those who share a common ancestor are predominantly homozygous‐by‐descent at the mutated BS locus, the negative correlation is interpreted to mean that the emergence of low‐SCE cells in BS in some way depends on the pre‐existence of compound heterozygosity. A corollary to this is that BS is genetically heterogeneous.