Arid
DOI10.1038/s41598-017-06387-6
Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus
Cipriani, Valentina1,2,3; Silva, Raquel S.1,2; Arno, Gavin1,2; Pontikos, Nikolas1,3; Kalhoro, Ambreen1,2; Valeina, Sandra4; Inashkina, Inna5; Audere, Mareta5,6; Rutka, Katrina5,6; Puech, Bernard7; Michaelides, Michel1,2; van Heyningen, Veronica1; Lace, Baiba5,8; Webster, Andrew R.1,2; Moore, Anthony T.1,2,9
通讯作者Cipriani, Valentina ; Webster, Andrew R. ; Moore, Anthony T.
来源期刊SCIENTIFIC REPORTS
ISSN2045-2322
出版年2017
卷号7
英文摘要

Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development.


类型Article
语种英语
国家England ; Latvia ; France ; Canada ; USA
收录类别SCI-E
WOS记录号WOS:000407180200013
WOS关键词INTEGRATIVE GENOMICS VIEWER ; FAMILY ; PRDM13 ; GENE ; RETINA ; PHENOTYPE ; MAPS
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
来源机构University of London
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/202334
作者单位1.UCL Inst Ophthalmol, London, England;
2.Moorfields Eye Hosp, London, England;
3.UCL Genet Inst, London, England;
4.Childrens Clin Univ Hosp, Riga, Latvia;
5.Latvian Biomed Res & Study Ctr, Riga, Latvia;
6.Riga Stradins Univ, Riga, Latvia;
7.CHU, Explorat Vis & Neuroophtalmol, Lille, France;
8.CHU Laval, Quebec City, PQ, Canada;
9.UCSF Sch Med, Ophthalmol Dept, San Francisco, CA 94143 USA
推荐引用方式
GB/T 7714
Cipriani, Valentina,Silva, Raquel S.,Arno, Gavin,et al. Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus[J]. University of London,2017,7.
APA Cipriani, Valentina.,Silva, Raquel S..,Arno, Gavin.,Pontikos, Nikolas.,Kalhoro, Ambreen.,...&Moore, Anthony T..(2017).Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus.SCIENTIFIC REPORTS,7.
MLA Cipriani, Valentina,et al."Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus".SCIENTIFIC REPORTS 7(2017).
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