AustralieFrV1, Main, Exploration, bibRecord, 004827

Association Mapping of the High-Grade Myopia MYP3 Locus Reveals Novel Candidates UHRF1BP1L, PTPRR, and PPFIA2

Identifieur interne : 004827 ( Main/Exploration ); précédent : 004826; suivant : 004828

Association Mapping of the High-Grade Myopia MYP3 Locus Reveals Novel Candidates UHRF1BP1L, PTPRR, and PPFIA2

Auteurs : Felicia Hawthorne ; Sheng Feng ; Ravikanth Metlapally ; Yi-Ju Li ; Khanh-Nhat Tran-Viet ; Jeremy A. Guggenheim ; Francois Malecaze ; Patrick Calvas ; Thomas Rosenberg ; David A. Mackey [Australie] ; Cristina Venturini [Royaume-Uni] ; Pirro G. Hysi [Royaume-Uni] ; Christopher J. Hammond [Royaume-Uni] ; Terri L. Young

Source :

Investigative Ophthalmology & Visual Science [ 0146-0404 ] ; 2013.

RBID : PMC:3621505

Abstract

Purpose.

Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21–23 by four independent linkage studies.

Methods.

We performed a genetic association study of the MYP3 locus in a family-based high-grade myopia cohort (n = 82) by genotyping 768 single-nucleotide polymorphisms (SNPs) within the linkage region. Qualitative testing for high-grade myopia (sphere ≤ −5 D affected, > −0.5 D unaffected) and quantitative testing on the average dioptric sphere were performed.

Results.

Several genetic markers were nominally significantly associated with high-grade myopia in qualitative testing, including rs3803036, a missense mutation in PTPRR (P = 9.1 × 10⁻⁴) and rs4764971, an intronic SNP in UHRF1BP1L (P = 6.1 × 10⁻⁴). Quantitative testing determined statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10⁻⁶); rs7134216, in the 3′ untranslated region (UTR) of DEPDC4 (P = 5.4 × 10⁻⁷); and rs17306116, an intronic SNP within PPFIA2 (P < 9 × 10⁻⁴). Independently conducted whole genome expression array analyses identified protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR).

Conclusions.

In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs4764971, was validated for quantitative association, and SNPs within PTPRR (quantitative) and PPFIA2 (qualitative and quantitative) approached significance. Three genes identified by our association study and supported by ocular expression and/or replication, UHRF1BP1L, PTPRR, and PPFIA2, are novel candidates for myopic development within the MYP3 locus that should be further studied.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621505

DOI: 10.1167/iovs.12-11102
PubMed: 23422819
PubMed Central: 3621505

Affiliations:

Le document en format XML

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 Locus Reveals Novel Candidates <italic>UHRF1BP1L</italic>
, <italic>PTPRR</italic>
, and <italic>PPFIA2</italic>
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<region type="région" nuts="1">Grand Londres</region>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Association Mapping of the High-Grade Myopia <italic>MYP3</italic>
 Locus Reveals Novel Candidates <italic>UHRF1BP1L</italic>
, <italic>PTPRR</italic>
, and <italic>PPFIA2</italic>
</title>
<author><name sortKey="Hawthorne, Felicia" sort="Hawthorne, Felicia" uniqKey="Hawthorne F" first="Felicia" last="Hawthorne">Felicia Hawthorne</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Feng, Sheng" sort="Feng, Sheng" uniqKey="Feng S" first="Sheng" last="Feng">Sheng Feng</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina; the</nlm:aff>
<wicri:noCountry code="subfield">North Carolina; the</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Metlapally, Ravikanth" sort="Metlapally, Ravikanth" uniqKey="Metlapally R" first="Ravikanth" last="Metlapally">Ravikanth Metlapally</name>
<affiliation><nlm:aff id="aff3">School of Optometry, University of California-Berkeley, Berkeley, California; the</nlm:aff>
<wicri:noCountry code="subfield">California; the</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tran Viet, Khanh Nhat" sort="Tran Viet, Khanh Nhat" uniqKey="Tran Viet K" first="Khanh-Nhat" last="Tran-Viet">Khanh-Nhat Tran-Viet</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Guggenheim, Jeremy A" sort="Guggenheim, Jeremy A" uniqKey="Guggenheim J" first="Jeremy A." last="Guggenheim">Jeremy A. Guggenheim</name>
<affiliation><nlm:aff id="aff4">School of Optometry, Hong Kong Polytechnic University, Hong Kong; the</nlm:aff>
<wicri:noCountry code="subfield">Hong Kong; the</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Malecaze, Francois" sort="Malecaze, Francois" uniqKey="Malecaze F" first="Francois" last="Malecaze">Francois Malecaze</name>
<affiliation><nlm:aff id="aff5">Institut National de la Santé et de la Recherche Médicale, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; the</nlm:aff>
<wicri:noCountry code="subfield">France; the</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Calvas, Patrick" sort="Calvas, Patrick" uniqKey="Calvas P" first="Patrick" last="Calvas">Patrick Calvas</name>
<affiliation><nlm:aff id="aff5">Institut National de la Santé et de la Recherche Médicale, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; the</nlm:aff>
<wicri:noCountry code="subfield">France; the</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Rosenberg, Thomas" sort="Rosenberg, Thomas" uniqKey="Rosenberg T" first="Thomas" last="Rosenberg">Thomas Rosenberg</name>
<affiliation><nlm:aff id="aff6">National Eye Clinic, Kennedy Institute, Hellerup, Denmark; the</nlm:aff>
<wicri:noCountry code="subfield">Denmark; the</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Mackey, David A" sort="Mackey, David A" uniqKey="Mackey D" first="David A." last="Mackey">David A. Mackey</name>
<affiliation wicri:level="4"><nlm:aff id="aff7">Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, Parkville, Victoria, Australia; the</nlm:aff>
<orgName type="university">Université de Melbourne</orgName>
<country>Australie</country>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Venturini, Cristina" sort="Venturini, Cristina" uniqKey="Venturini C" first="Cristina" last="Venturini">Cristina Venturini</name>
<affiliation><nlm:aff id="aff8">Institute of Ophthalmology, University College of London, London, United Kingdom; the</nlm:aff>
<wicri:noCountry code="subfield">United Kingdom; the</wicri:noCountry>
</affiliation>
<affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff9">Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hysi, Pirro G" sort="Hysi, Pirro G" uniqKey="Hysi P" first="Pirro G." last="Hysi">Pirro G. Hysi</name>
<affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff9">Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hammond, Christopher J" sort="Hammond, Christopher J" uniqKey="Hammond C" first="Christopher J." last="Hammond">Christopher J. Hammond</name>
<affiliation wicri:level="3"><nlm:aff wicri:cut="; and" id="aff9">Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Young, Terri L" sort="Young, Terri L" uniqKey="Young T" first="Terri L." last="Young">Terri L. Young</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff10">Duke Eye Center, Duke University Health System, Durham, North Carolina.</nlm:aff>
<wicri:noCountry code="subfield">North Carolina.</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">Investigative Ophthalmology & Visual Science</title>
<idno type="ISSN">0146-0404</idno>
<idno type="eISSN">1552-5783</idno>
<imprint><date when="2013">2013</date>
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<front><div type="abstract" xml:lang="en"><sec id="st1"><title>Purpose.</title>
<p>Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, <italic>MYP3</italic>
, has been reported on chromosome 12q21–23 by four independent linkage studies.</p>
</sec>
<sec id="st2"><title>Methods.</title>
<p>We performed a genetic association study of the <italic>MYP3</italic>
 locus in a family-based high-grade myopia cohort (<italic>n</italic>
 = 82) by genotyping 768 single-nucleotide polymorphisms (SNPs) within the linkage region. Qualitative testing for high-grade myopia (sphere ≤ −5 D affected, > −0.5 D unaffected) and quantitative testing on the average dioptric sphere were performed.</p>
</sec>
<sec id="st3"><title>Results.</title>
<p>Several genetic markers were nominally significantly associated with high-grade myopia in qualitative testing, including <italic>rs3803036</italic>
, a missense mutation in <italic>PTPRR</italic>
 (<italic>P</italic>
 = 9.1 × 10<sup>−<bold>4</bold>
</sup>
) and <italic>rs4764971</italic>
, an intronic SNP in <italic>UHRF1BP1L</italic>
 (<italic>P</italic>
 = 6.1 × 10<sup>−4</sup>
). Quantitative testing determined statistically significant SNPs <italic>rs4764971</italic>
, also found by qualitative testing (<italic>P</italic>
 = 3.1 × 10<sup>−6</sup>
); <italic>rs7134216</italic>
, in the 3′ untranslated region (UTR) of <italic>DEPDC4</italic>
 (<italic>P</italic>
 = 5.4 × 10<sup>−7</sup>
); and <italic>rs17306116</italic>
, an intronic SNP within <italic>PPFIA2</italic>
 (<italic>P</italic>
 < 9 × 10<sup>−4</sup>
). Independently conducted whole genome expression array analyses identified protein tyrosine phosphatase genes <italic>PTPRR</italic>
 and <italic>PPFIA2</italic>
, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR).</p>
</sec>
<sec id="st4"><title>Conclusions.</title>
<p>In an independent high-grade myopia cohort, an intronic SNP in <italic>UHRF1BP1L</italic>
, <italic>rs4764971</italic>
, was validated for quantitative association, and SNPs within <italic>PTPRR</italic>
 (quantitative) and <italic>PPFIA2</italic>
 (qualitative and quantitative) approached significance. Three genes identified by our association study and supported by ocular expression and/or replication, <italic>UHRF1BP1L</italic>
, <italic>PTPRR</italic>
, and <italic>PPFIA2</italic>
, are novel candidates for myopic development within the <italic>MYP3</italic>
 locus that should be further studied.</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Royaume-Uni</li>
</country>
<region><li>Angleterre</li>
<li>Grand Londres</li>
<li>Victoria (État)</li>
</region>
<settlement><li>Londres</li>
<li>Melbourne</li>
</settlement>
<orgName><li>Université de Melbourne</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Calvas, Patrick" sort="Calvas, Patrick" uniqKey="Calvas P" first="Patrick" last="Calvas">Patrick Calvas</name>
<name sortKey="Feng, Sheng" sort="Feng, Sheng" uniqKey="Feng S" first="Sheng" last="Feng">Sheng Feng</name>
<name sortKey="Guggenheim, Jeremy A" sort="Guggenheim, Jeremy A" uniqKey="Guggenheim J" first="Jeremy A." last="Guggenheim">Jeremy A. Guggenheim</name>
<name sortKey="Hawthorne, Felicia" sort="Hawthorne, Felicia" uniqKey="Hawthorne F" first="Felicia" last="Hawthorne">Felicia Hawthorne</name>
<name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name>
<name sortKey="Malecaze, Francois" sort="Malecaze, Francois" uniqKey="Malecaze F" first="Francois" last="Malecaze">Francois Malecaze</name>
<name sortKey="Metlapally, Ravikanth" sort="Metlapally, Ravikanth" uniqKey="Metlapally R" first="Ravikanth" last="Metlapally">Ravikanth Metlapally</name>
<name sortKey="Rosenberg, Thomas" sort="Rosenberg, Thomas" uniqKey="Rosenberg T" first="Thomas" last="Rosenberg">Thomas Rosenberg</name>
<name sortKey="Tran Viet, Khanh Nhat" sort="Tran Viet, Khanh Nhat" uniqKey="Tran Viet K" first="Khanh-Nhat" last="Tran-Viet">Khanh-Nhat Tran-Viet</name>
<name sortKey="Young, Terri L" sort="Young, Terri L" uniqKey="Young T" first="Terri L." last="Young">Terri L. Young</name>
</noCountry>
<country name="Australie"><region name="Victoria (État)"><name sortKey="Mackey, David A" sort="Mackey, David A" uniqKey="Mackey D" first="David A." last="Mackey">David A. Mackey</name>
</region>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Venturini, Cristina" sort="Venturini, Cristina" uniqKey="Venturini C" first="Cristina" last="Venturini">Cristina Venturini</name>
</region>
<name sortKey="Hammond, Christopher J" sort="Hammond, Christopher J" uniqKey="Hammond C" first="Christopher J." last="Hammond">Christopher J. Hammond</name>
<name sortKey="Hysi, Pirro G" sort="Hysi, Pirro G" uniqKey="Hysi P" first="Pirro G." last="Hysi">Pirro G. Hysi</name>
</country>
</tree>
</affiliations>
</record>

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   |texte=   Association Mapping of the High-Grade Myopia MYP3 Locus Reveals Novel Candidates UHRF1BP1L, PTPRR, and PPFIA2
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Association Mapping of the High-Grade Myopia MYP3 Locus Reveals Novel Candidates UHRF1BP1L, PTPRR, and PPFIA2

Association Mapping of the High-Grade Myopia MYP3 Locus Reveals Novel Candidates UHRF1BP1L, PTPRR, and PPFIA2

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	Serveur d'exploration sur les relations entre la France et l'Australie
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