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Population mutation scanning of human GHR by meltMADGE and identification of a paucimorphic variant

Population mutation scanning of human GHR by meltMADGE and identification of a paucimorphic variant
Population mutation scanning of human GHR by meltMADGE and identification of a paucimorphic variant
Current studies of human genetic diversity are focused in two areas: first, detection of rare mutations in highly selected clinical cases; and second, in common single-nucleotide polymorphism (SNP) and haplotype effects in the general population. Less frequent SNPs and "paucimorphisms" remain underexplored, although lower frequency coding SNPs are more likely to have functional impact. We have developed a cost-efficient mutation scanning technology, meltMADGE, for population mutation scanning. Previous research in GHR has explored its role in extreme (-3 SD) growth retardation and, subsequently, "moderate" (-2 SD) growth retardation cases. Here, we describe meltMADGE assays for the entire coding region of GHR. As a first step we have established long polymerase chain reaction subbanks for GHR from 2423 unselected subjects and have applied meltMADGE scanning assays of exons 4 and 5 to these subbanks. A novel paucimorphism present at 439+30A>C (allele frequency: 0.0021) in intron 5 (location chr5:42,695,221 in GRCh37/hg19) was identified in 10 individuals, confirmed by sequencing and analysis made for major phenotypic effects. This approach is relevant to the deep sampling of populations for less frequent sequence diversity, some of which is expected to exert significant phenotypic effects.

1945-0265
855-860
Alharbi, Khalid K.
f8267cbb-ad0a-4ad8-b483-ff896223dfda
Hou, Guangwei
931a83d2-65a0-4574-95d5-02d872e99187
Chen, Xiao-he
fd93b896-d8cc-4b0e-a811-c0e6a8ff8308
Gaunt, Tom R.
ff4bc39d-405c-4ba1-896b-7e7d2f747387
Syddall, Holly E.
a0181a93-8fc3-4998-a996-7963f0128328
Sayer, Avan Aihie
fb4c2053-6d51-4fc1-9489-c3cb431b0ffb
Dennison, Elaine M.
ee647287-edb4-4392-8361-e59fd505b1d1
Phillips, David I. W.
29b73be7-2ff9-4fff-ae42-d59842df4cc6
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Day, Ian N. W.
3063bfd2-a3b5-41f5-98e5-3695b06a0dc3
Alharbi, Khalid K.
f8267cbb-ad0a-4ad8-b483-ff896223dfda
Hou, Guangwei
931a83d2-65a0-4574-95d5-02d872e99187
Chen, Xiao-he
fd93b896-d8cc-4b0e-a811-c0e6a8ff8308
Gaunt, Tom R.
ff4bc39d-405c-4ba1-896b-7e7d2f747387
Syddall, Holly E.
a0181a93-8fc3-4998-a996-7963f0128328
Sayer, Avan Aihie
fb4c2053-6d51-4fc1-9489-c3cb431b0ffb
Dennison, Elaine M.
ee647287-edb4-4392-8361-e59fd505b1d1
Phillips, David I. W.
29b73be7-2ff9-4fff-ae42-d59842df4cc6
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Day, Ian N. W.
3063bfd2-a3b5-41f5-98e5-3695b06a0dc3

Alharbi, Khalid K., Hou, Guangwei, Chen, Xiao-he, Gaunt, Tom R., Syddall, Holly E., Sayer, Avan Aihie, Dennison, Elaine M., Phillips, David I. W., Cooper, Cyrus and Day, Ian N. W. (2011) Population mutation scanning of human GHR by meltMADGE and identification of a paucimorphic variant. Genetic Testing and Molecular Biomarkers, 15, 855-860. (PMID:21689014)

Record type: Article

Abstract

Current studies of human genetic diversity are focused in two areas: first, detection of rare mutations in highly selected clinical cases; and second, in common single-nucleotide polymorphism (SNP) and haplotype effects in the general population. Less frequent SNPs and "paucimorphisms" remain underexplored, although lower frequency coding SNPs are more likely to have functional impact. We have developed a cost-efficient mutation scanning technology, meltMADGE, for population mutation scanning. Previous research in GHR has explored its role in extreme (-3 SD) growth retardation and, subsequently, "moderate" (-2 SD) growth retardation cases. Here, we describe meltMADGE assays for the entire coding region of GHR. As a first step we have established long polymerase chain reaction subbanks for GHR from 2423 unselected subjects and have applied meltMADGE scanning assays of exons 4 and 5 to these subbanks. A novel paucimorphism present at 439+30A>C (allele frequency: 0.0021) in intron 5 (location chr5:42,695,221 in GRCh37/hg19) was identified in 10 individuals, confirmed by sequencing and analysis made for major phenotypic effects. This approach is relevant to the deep sampling of populations for less frequent sequence diversity, some of which is expected to exert significant phenotypic effects.

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More information

Published date: 1 December 2011
Organisations: Faculty of Health Sciences

Identifiers

Local EPrints ID: 208259
URI: https://eprints.soton.ac.uk/id/eprint/208259
ISSN: 1945-0265
PURE UUID: d23c5dcc-e0ba-4e93-af29-1c3dcc2a26c1
ORCID for Holly E. Syddall: ORCID iD orcid.org/0000-0003-0171-0306
ORCID for Elaine M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 17 Jan 2012 15:17
Last modified: 20 Jul 2019 01:17

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Contributors

Author: Khalid K. Alharbi
Author: Guangwei Hou
Author: Xiao-he Chen
Author: Tom R. Gaunt
Author: David I. W. Phillips
Author: Cyrus Cooper ORCID iD
Author: Ian N. W. Day

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