Abstract
Here we report recruitment of a three-generation Romani (Gypsy) family with autosomal dominant cone-rod dystrophy (adCORD). Involvement of known adCORD genes was excluded by microsatellite (STR) genotyping and linkage analysis. Subsequently, two independent total-genome scans using STR markers and single-nucleotide polymorphisms (SNPs) were performed. Haplotype analysis revealed a single 6.7-Mb novel locus between markers D10S1757 and D10S1782 linked to the disease phenotype on chromosome 10q26. Linkage analysis gave a maximum LOD score of 3.31 for five fully informative STR markers within the linked interval corresponding to the expected maximum in the family. Multipoint linkage analysis of SNP genotypes yielded a maximum parametric linkage score of 2.71 with markers located in the same chromosomal interval. There is no previously mapped CORD locus in this interval, and therefore the data reported here is novel and likely to identify a new gene that may eventually contribute to new knowledge on the pathogenesis of this condition. Sequencing of several candidate genes within the mapped interval led to negative findings in terms of the underlying molecular pathogenesis of the disease in the family. Analysis by comparative genomic hybridization excluded large chromosomal aberrations as causative of adCORD in the pedigree.
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Acknowledgements
We thank the Romani patients and their family for taking part in this research. Also we thank the Ethnic Minorities Health Problems Foundation’s team (Bulgaria), Beverly Scott and Valentin Panchev for their excellent technical assistance. We would like to acknowledge the technical assistance of Daniela Dacheva and Stanislava Dimitrova from Molecular Medicine Center. This work was supported by grants from: Fundacíon Progresso y Salud (Project No: 113.GI02.0.0000), Spain; Foundation Fighting Blindness (USA); RP Fighting Blindness (UK); National Science Fund, Bulgarian Ministry of Education, Youth and Science (Contract G-3/2004). The Molecular Medicine Center was supported by infrastructure grants from: National Science Fund, Bulgarian Ministry of Education, Youth and Science (DUNK01-2/2009) and the Science Fund, Medical University – Sofia (8I/2009).
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Kamenarova, K., Cherninkova, S., Romero Durán, M. et al. A novel locus for autosomal dominant cone-rod dystrophy maps to chromosome 10q. Eur J Hum Genet 21, 338–342 (2013). https://doi.org/10.1038/ejhg.2012.158
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DOI: https://doi.org/10.1038/ejhg.2012.158
