Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus

Simple item page
dc.contributor.authorCipriani, Valentina
dc.contributor.authorSilva, Raquel S.
dc.contributor.authorArno, Gavin
dc.contributor.authorPontikos, Nikolas
dc.contributor.authorKalhoro, Ambreen
dc.contributor.authorValeina, Sandra
dc.contributor.authorInashkina, Inna
dc.contributor.authorAudere, Mareta
dc.contributor.authorRutka, Katrina
dc.contributor.authorPuech, Bernard
dc.contributor.authorMichaelides, Michel
dc.contributor.authorVan Heyningen, Veronica
dc.contributor.authorLace, Baiba
dc.contributor.authorWebster, Andrew R.
dc.contributor.authorMoore, Anthony T.
dc.contributor.institutionRīga Stradiņš University
dc.date.accessioned2021-09-14T09:55:01Z
dc.date.available2021-09-14T09:55:01Z
dc.date.issued2017-12-01
dc.descriptionPublisher Copyright: © 2017 The Author(s).
dc.description.abstractAutosomal 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.en
dc.description.statusPeer reviewed
dc.format.extent9
dc.format.extent1671496
dc.identifier.citationCipriani, V, Silva, R S, Arno, G, Pontikos, N, Kalhoro, A, Valeina, S, Inashkina, I, Audere, M, Rutka, K, Puech, B, Michaelides, M, Van Heyningen, V, Lace, B, Webster, A R & Moore, A T 2017, 'Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus', Scientific Reports, vol. 7, no. 1, 7512. https://doi.org/10.1038/s41598-017-06387-6
dc.identifier.doi10.1038/s41598-017-06387-6
dc.identifier.issn2045-2322
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/6339
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85027037545&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofScientific Reports
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.2 Clinical medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectGeneral
dc.subjectSDG 3 - Good Health and Well-being
dc.titleDuplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locusen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Duplication_events_downstream_of_IRX1_cause.pdf
Size:
1.59 MB
Format:
Adobe Portable Document Format
Download

Collections

Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure