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Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2

Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2
Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2
Copy number variants visible with the light microscope have been described as euchromatic variants (EVs) and EVs with extra G-light material at 8q21.2 have been reported only once before. We report four further patients with EVs of 8q21.2 ascertained for clinical (3) or reproductive reasons (1). Enhanced signal strength from two overlapping bacterial artificial chromosomes (BACs) and microarray analysis mapped the EV to a 284-kb interval in the reference genome. This interval consists of a sequence gap flanked by segmental duplications that contain the 12-kb components of one of the largest Variable Number Tandem Repeat arrays in the human genome. Using digital NanoString technology with a custom probe for the RNA exonuclease 1 homologue (S. cerevisiae)-like 1 (REXO1L1) gene within each 12-kb repeat, significantly enhanced diploid copy numbers of 270 and 265 were found in an EV family and a median diploid copy number of 166 copies in 216 controls. These 8q21.2 EVs are not thought to have clinical consequences as the phenotypes of the probands were inconsistent, those referred for reproductive reasons were otherwise phenotypically normal and the REXO1L1 gene has no known disease association. This EV was found in 4/3078 (1 in 770) consecutive referrals for chromosome analysis and needs to be distinguished from pathogenic imbalances of medial 8q. The REXO1L1 gene product is a marker of hepatitis C virus (HCV) infection and a possible association between REXO1L1 copy number and susceptibility to HCV infection, progression or response to treatment has not yet been excluded.
8q21.2, copy number variant, euchromatic variant, dna array, nanostring technology, REXO1L1, hepatitis c
1018-4813
458-463
Tyson, Christine
58b11f2c-c09a-4a59-93d9-cc2ec31977cc
Sharp, Andrew J.
4f814cb9-0069-4850-ad81-5ad57435f414
Hrynchak, Monica
b2484204-7124-45bd-a49d-3e6ec065fe60
Yong, Siu L.
e2e07cb0-ad54-4d2c-b938-fcc73fea4170
Hollox, Edward J.
a07bae66-67dc-4c2c-a655-500ee79f081b
Warburton, Peter
630ee512-b1c6-4adc-92e6-f15ab03a7e66
Barber, John C.K.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Tyson, Christine
58b11f2c-c09a-4a59-93d9-cc2ec31977cc
Sharp, Andrew J.
4f814cb9-0069-4850-ad81-5ad57435f414
Hrynchak, Monica
b2484204-7124-45bd-a49d-3e6ec065fe60
Yong, Siu L.
e2e07cb0-ad54-4d2c-b938-fcc73fea4170
Hollox, Edward J.
a07bae66-67dc-4c2c-a655-500ee79f081b
Warburton, Peter
630ee512-b1c6-4adc-92e6-f15ab03a7e66
Barber, John C.K.
4785a6e4-bd63-4230-ab61-41a0ae12c761

Tyson, Christine, Sharp, Andrew J., Hrynchak, Monica, Yong, Siu L., Hollox, Edward J., Warburton, Peter and Barber, John C.K. (2014) Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2. European Journal of Human Genetics, 22 (4), 458-463. (doi:10.1038/ejhg.2013.185). (PMID:24045839)

Record type: Article

Abstract

Copy number variants visible with the light microscope have been described as euchromatic variants (EVs) and EVs with extra G-light material at 8q21.2 have been reported only once before. We report four further patients with EVs of 8q21.2 ascertained for clinical (3) or reproductive reasons (1). Enhanced signal strength from two overlapping bacterial artificial chromosomes (BACs) and microarray analysis mapped the EV to a 284-kb interval in the reference genome. This interval consists of a sequence gap flanked by segmental duplications that contain the 12-kb components of one of the largest Variable Number Tandem Repeat arrays in the human genome. Using digital NanoString technology with a custom probe for the RNA exonuclease 1 homologue (S. cerevisiae)-like 1 (REXO1L1) gene within each 12-kb repeat, significantly enhanced diploid copy numbers of 270 and 265 were found in an EV family and a median diploid copy number of 166 copies in 216 controls. These 8q21.2 EVs are not thought to have clinical consequences as the phenotypes of the probands were inconsistent, those referred for reproductive reasons were otherwise phenotypically normal and the REXO1L1 gene has no known disease association. This EV was found in 4/3078 (1 in 770) consecutive referrals for chromosome analysis and needs to be distinguished from pathogenic imbalances of medial 8q. The REXO1L1 gene product is a marker of hepatitis C virus (HCV) infection and a possible association between REXO1L1 copy number and susceptibility to HCV infection, progression or response to treatment has not yet been excluded.

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More information

e-pub ahead of print date: 18 September 2013
Published date: April 2014
Keywords: 8q21.2, copy number variant, euchromatic variant, dna array, nanostring technology, REXO1L1, hepatitis c
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 359146
URI: http://eprints.soton.ac.uk/id/eprint/359146
ISSN: 1018-4813
PURE UUID: 6e36dda0-0806-4035-bd36-0d19764650af

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Date deposited: 23 Oct 2013 08:43
Last modified: 14 Mar 2024 15:17

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Contributors

Author: Christine Tyson
Author: Andrew J. Sharp
Author: Monica Hrynchak
Author: Siu L. Yong
Author: Edward J. Hollox
Author: Peter Warburton
Author: John C.K. Barber

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