Systematic re-examination of carriers of balanced reciprocal translocations: a strategy to search for candidate regions for common and complex diseases.
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.
Bache
Iben
I
Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Biochemistry and Genetics, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. iben@medgen.ku.dk
Hjorth
Mads
M
Bugge
Merete
M
Holstebroe
Søren
S
Hilden
Jørgen
J
Schmidt
Lone
L
Brondum-Nielsen
Karen
K
Bruun-Petersen
Gert
G
Jensen
Peter K A
PK
Lundsteen
Claes
C
Niebuhr
Erik
E
Rasmussen
Kirsten
K
Tommerup
Niels
N
D017668:Age of Onset; D002874:Chromosome Mapping; D015331:Cohort Studies; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D010375:Pedigree; D011795:Surveys and Questionnaires; D014178:Translocation, Genetic