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DOI | 10.1038/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
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ISSN | 2045-2322 |
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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