Systematic re-examination of carriers of balanced reciprocal translocations: a strategy to search for candidate regions for common and complex diseases

TY - JOUR

T1 - Systematic re-examination of carriers of balanced reciprocal translocations: a strategy to search for candidate regions for common and complex diseases

AU - Bache, Iben

AU - Hjorth, Mads

AU - Bugge, Merete

AU - Holstebroe, Søren

AU - Hilden, Jørgen

AU - Schmidt, Lone

AU - Brondum-Nielsen, Karen

AU - Bruun-Petersen, Gert

AU - Jensen, Peter K A

AU - Lundsteen, Claes

AU - Niebuhr, Erik

AU - Rasmussen, Kirsten

AU - Tommerup, Niels

N1 - Keywords: Age of Onset; Chromosome Mapping; Cohort Studies; Female; Heterozygote Detection; Humans; Male; Pedigree; Questionnaires; Translocation, Genetic

PY - 2006

Y1 - 2006

N2 - Balanced reciprocal translocations associated with genetic disorders have facilitated the identification of a variety of genes for early-onset monogenic disorders, but only rarely the genes associated with common and complex disorders. To assess the potential of chromosomal breakpoints associated with common/ complex disorders, we investigated the full spectrum of diseases in 731 carriers of balanced reciprocal translocations without known early-onset disorders in a nation-wide questionnaire-based re-examination. In 42 families, one of the breakpoints at the cytogenetic level concurred with known linkage data and/or the translocation co-segregated with the reported phenotype, for example, we found a significant linkage (lod score=2.1) of dyslexia and a co-segregating translocation with a breakpoint in a previously confirmed locus for dyslexia. Furthermore, we identified 441 instances of at least two unrelated carriers with concordant breakpoints and traits. If applied to other populations, re-examination of translocation carriers may identify additional genotype-phenotype associations, some of which may be novel and others that may coincide with and provide additional support of data presented here.

AB - Balanced reciprocal translocations associated with genetic disorders have facilitated the identification of a variety of genes for early-onset monogenic disorders, but only rarely the genes associated with common and complex disorders. To assess the potential of chromosomal breakpoints associated with common/ complex disorders, we investigated the full spectrum of diseases in 731 carriers of balanced reciprocal translocations without known early-onset disorders in a nation-wide questionnaire-based re-examination. In 42 families, one of the breakpoints at the cytogenetic level concurred with known linkage data and/or the translocation co-segregated with the reported phenotype, for example, we found a significant linkage (lod score=2.1) of dyslexia and a co-segregating translocation with a breakpoint in a previously confirmed locus for dyslexia. Furthermore, we identified 441 instances of at least two unrelated carriers with concordant breakpoints and traits. If applied to other populations, re-examination of translocation carriers may identify additional genotype-phenotype associations, some of which may be novel and others that may coincide with and provide additional support of data presented here.

U2 - 10.1038/sj.ejhg.5201592

DO - 10.1038/sj.ejhg.5201592

M3 - Journal article

C2 - 16493440

SN - 1018-4813

VL - 14

SP - 410

EP - 417

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 4

ER -