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.
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
Iben
I
Bache
Mads
M
Hjorth
Merete
M
Bugge
Søren
S
Holstebroe
Jørgen
J
Hilden
Lone
L
Schmidt
Karen
K
Brondum-Nielsen
Gert
G
Bruun-Petersen
Peter K A
PK
Jensen
Claes
C
Lundsteen
Erik
E
Niebuhr
Kirsten
K
Rasmussen
Niels
N
Tommerup
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