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De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy

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Abstract
X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L-and M-cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of >= 20% of transcripts including the known pathogenic haplotypes (i.e. 'LIAVA', 'LVAVA') with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the 'LIAVA' haplotype derived from an ancestral less deleterious 'LIAVS' haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.
Keywords
GREEN OPSIN GENES, HUMAN RED, HUMAN COLOR-VISION, SEGMENTAL DUPLICATIONS, MOLECULAR-GENETICS, PIGMENT GENES, ARRAY, MUTATIONS, VARIANTS, EVOLUTION

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Chicago
Buena-Atienza, Elena, Klaus Rüther, Britta Baumann, Richard Bergholz, David Birch, Elfride De Baere, Helene Dollfus, et al. 2016. “De Novo Intrachromosomal Gene Conversion from OPN1MW to OPN1LW in the Male Germline Results in Blue Cone Monochromacy.” Scientific Reports 6.
APA
Buena-Atienza, E., Rüther, K., Baumann, B., Bergholz, R., Birch, D., De Baere, E., Dollfus, H., et al. (2016). De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy. SCIENTIFIC REPORTS, 6.
Vancouver
1.
Buena-Atienza E, Rüther K, Baumann B, Bergholz R, Birch D, De Baere E, et al. De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy. SCIENTIFIC REPORTS. 2016;6.
MLA
Buena-Atienza, Elena, Klaus Rüther, Britta Baumann, et al. “De Novo Intrachromosomal Gene Conversion from OPN1MW to OPN1LW in the Male Germline Results in Blue Cone Monochromacy.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.
@article{8099546,
  abstract     = {X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L-and M-cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of {\textrangle}= 20\% of transcripts including the known pathogenic haplotypes (i.e. 'LIAVA', 'LVAVA') with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the 'LIAVA' haplotype derived from an ancestral less deleterious 'LIAVS' haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.},
  articleno    = {28253},
  author       = {Buena-Atienza, Elena and R{\"u}ther, Klaus and Baumann, Britta and Bergholz, Richard and Birch, David and De Baere, Elfride and Dollfus, Helene and Greally, Marie T and Gustavsson, Peter and Hamel, Christian P and Heckenlively, John R and Leroy, Bart and Plomp, Astrid S and Pott, Jan Willem R and Rose, Katherine and Rosenberg, Thomas and Stark, Zornitza and Verheij, Joke BGM and Weleber, Richard and Zobor, Ditta and Weisschuh, Nicole and Kohl, Susanne and Wissinger, Bernd},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {GREEN OPSIN GENES,HUMAN RED,HUMAN COLOR-VISION,SEGMENTAL DUPLICATIONS,MOLECULAR-GENETICS,PIGMENT GENES,ARRAY,MUTATIONS,VARIANTS,EVOLUTION},
  language     = {eng},
  pages        = {11},
  title        = {De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy},
  url          = {http://dx.doi.org/10.1038/srep28253},
  volume       = {6},
  year         = {2016},
}

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