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

• Published in: European journal of human genetics : EJHG Vol. 14; no. 4; pp. 410 - 417
• Main Authors: Bache, Iben, Hjorth, Mads, Bugge, Merete, Holstebroe, Søren, Hilden, Jørgen, Schmidt, Lone, Brondum-Nielsen, Karen, Bruun-Petersen, Gert, Jensen, Peter K A, Lundsteen, Claes, Niebuhr, Erik, Rasmussen, Kirsten, Tommerup, Niels
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2006; Nature Publishing; Nature Publishing Group
• Subjects: Age; Age of Onset; Biochemistry; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bipolar disorder; Breakpoints; Chromosome aberrations; Chromosome Mapping; Chromosome translocations; Chromosomes; Cohort Studies; Cytogenetics; Dyslexia; Epidemiology; Female; Gene Expression; General aspects. Genetic counseling; Genetic Carrier Screening; Genetics; Genomes; Genomics; Genotypes; Human Genetics; Humans; Male; Medical genetics; Medical sciences; Pedigree; Phenotypes; Population; Questionnaires; Studies; Surveys and Questionnaires; Translocation, Genetic; Denmark; late-onset disorders; reciprocal translocation; questionnaire-based study; complex diseases; clinical epidemiology; Chromosomal aberration; Late; Questionnaire; Epidemiology; Genetic disease; Genetic counseling; Abnormal chromosome; Genetics; Strategy; Carrier; Complex syndrome; Chromosome translocation
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/sj.ejhg.5201592

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.