Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/10139
Full metadata record
DC FieldValueLanguage
dc.contributor.authorMacLean, Helen Een
dc.contributor.authorFavaloro, Jenny Men
dc.contributor.authorWarne, Garry Len
dc.contributor.authorZajac, Jeffrey Den
dc.date.accessioned2015-05-15T23:29:43Z
dc.date.available2015-05-15T23:29:43Z
dc.date.issued2006-05-01en
dc.identifier.citationHuman Mutation; 27(5): 483-9en
dc.identifier.govdoc16619235en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/10139en
dc.description.abstractWe have characterized an unusual family with two different androgen receptor (AR) gene deletions, in which we propose a novel mechanism of deletion formation has occurred. Affected individuals have the X-linked disorder androgen insensitivity syndrome, and we previously showed that different family members have deletions of different exons of the AR gene. We have now fully sequenced the deletions from affected individuals, and confirmed the presence of different deletions in different affected family members. Most affected and heterozygote individuals have a 4,430-bp deletion of exon 5 that occurred between repeated GTGGCAT motifs in introns 4 and 5. One affected hemizygous individual has a 4,033-bp deletion of exons 6 and 7 that occurred between repeated CCTC motifs in introns 5 and 7. The intron 5 breakpoint junctions of the two deletions are only 11 bp apart. Surprisingly, the maternal grandmother of the original index case was found to be mosaic for both deletional events, as well as having the normal AR gene. Karyotyping ruled out 47,XXX trisomy, indicating triple mosaicism for the two different deleted AR alleles and a normal AR allele. This triple mosaicism must have occurred early in embryonic development, as both deletions were passed on to different children. Based on these findings, we propose a novel mechanism of deletion formation. We suggest that during AR gene replication, a double strand DNA break occurred in intron 5, and that a variant of replication slippage occurred on both newly synthesized strands between the repeat motifs of microhomology, leading to the formation of the two different AR gene deletions.en
dc.language.isoenen
dc.subject.otherAndrogen-Insensitivity Syndrome.geneticsen
dc.subject.otherChromosomes, Human, Xen
dc.subject.otherDNA Mutational Analysisen
dc.subject.otherDNA Repairen
dc.subject.otherDNA Replication.physiologyen
dc.subject.otherExonsen
dc.subject.otherFemaleen
dc.subject.otherGene Deletionen
dc.subject.otherGenetic Linkageen
dc.subject.otherHeterozygoteen
dc.subject.otherHumansen
dc.subject.otherKaryotypingen
dc.subject.otherMaleen
dc.subject.otherMolecular Sequence Dataen
dc.subject.otherMosaicismen
dc.subject.otherPedigreeen
dc.subject.otherReceptors, Androgen.geneticsen
dc.titleDouble-strand DNA break repair with replication slippage on two strands: a novel mechanism of deletion formation.en
dc.typeJournal Articleen
dc.identifier.journaltitleHuman mutationen
dc.identifier.affiliationDepartment of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australiaen
dc.identifier.doi10.1002/humu.20327en
dc.description.pages483-9en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/16619235en
dc.type.austinJournal Articleen
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
item.grantfulltextnone-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
crisitem.author.deptEndocrinology-
crisitem.author.deptMedicine (University of Melbourne)-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

2
checked on Jan 29, 2023

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.