---
_id: '2250'
abstract:
- lang: eng
  text: The genome sequences of new viruses often contain many "orphan"
    or "taxon-specific" proteins apparently lacking homologs. However, because
    viral proteins evolve very fast, commonly used sequence similarity detection methods
    such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA
    viruses characterized as "genus specific" by BLAST. More powerful methods
    developed recently, such as HHblits or HHpred (available through web-based, user-friendly
    interfaces), could detect distant homologs of a quarter of these proteins, suggesting
    that these methods should be used to annotate viral genomes. In-depth manual analyses
    of a subset of the remaining sequences, guided by contextual information such
    as taxonomy, gene order, or domain cooccurrence, identified distant homologs of
    another third. Thus, a combination of powerful automated methods and manual analyses
    can uncover distant homologs of many proteins thought to be orphans. We expect
    these methodological results to be also applicable to cellular organisms, since
    they generally evolve much more slowly than RNA viruses. As an application, we
    reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We
    could identify homologs of most of its proteins thought to be orphans; in each
    case, identifying homologs provided functional clues. We discovered that CBPV
    encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase;
    a putative membrane protein, SP24, with homologs in unrelated insect viruses and
    insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses,
    blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found
    in negeviruses. SP24 and ORF2 are probably major structural components of the
    virionsd.
author:
- first_name: Durga
  full_name: Kuchibhatla, Durga
  last_name: Kuchibhatla
- first_name: Westley
  full_name: Sherman, Westley
  last_name: Sherman
- first_name: Betty
  full_name: Chung, Betty
  last_name: Chung
- first_name: Shelley
  full_name: Cook, Shelley
  last_name: Cook
- first_name: Georg
  full_name: Schneider, Georg
  id: 329095A0-F248-11E8-B48F-1D18A9856A87
  last_name: Schneider
- first_name: Birgit
  full_name: Eisenhaber, Birgit
  last_name: Eisenhaber
- first_name: David
  full_name: Karlin, David
  last_name: Karlin
citation:
  ama: Kuchibhatla D, Sherman W, Chung B, et al. Powerful sequence similarity search
    methods and in-depth manual analyses can identify remote homologs in many apparently
    “orphan” viral proteins. <i>Journal of Virology</i>. 2014;88(1):10-20. doi:<a
    href="https://doi.org/10.1128/JVI.02595-13">10.1128/JVI.02595-13</a>
  apa: Kuchibhatla, D., Sherman, W., Chung, B., Cook, S., Schneider, G., Eisenhaber,
    B., &#38; Karlin, D. (2014). Powerful sequence similarity search methods and in-depth
    manual analyses can identify remote homologs in many apparently “orphan” viral
    proteins. <i>Journal of Virology</i>. ASM. <a href="https://doi.org/10.1128/JVI.02595-13">https://doi.org/10.1128/JVI.02595-13</a>
  chicago: Kuchibhatla, Durga, Westley Sherman, Betty Chung, Shelley Cook, Georg Schneider,
    Birgit Eisenhaber, and David Karlin. “Powerful Sequence Similarity Search Methods
    and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently ‘Orphan’
    Viral Proteins.” <i>Journal of Virology</i>. ASM, 2014. <a href="https://doi.org/10.1128/JVI.02595-13">https://doi.org/10.1128/JVI.02595-13</a>.
  ieee: D. Kuchibhatla <i>et al.</i>, “Powerful sequence similarity search methods
    and in-depth manual analyses can identify remote homologs in many apparently ‘orphan’
    viral proteins,” <i>Journal of Virology</i>, vol. 88, no. 1. ASM, pp. 10–20, 2014.
  ista: Kuchibhatla D, Sherman W, Chung B, Cook S, Schneider G, Eisenhaber B, Karlin
    D. 2014. Powerful sequence similarity search methods and in-depth manual analyses
    can identify remote homologs in many apparently ‘orphan’ viral proteins. Journal
    of Virology. 88(1), 10–20.
  mla: Kuchibhatla, Durga, et al. “Powerful Sequence Similarity Search Methods and
    In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently ‘Orphan’
    Viral Proteins.” <i>Journal of Virology</i>, vol. 88, no. 1, ASM, 2014, pp. 10–20,
    doi:<a href="https://doi.org/10.1128/JVI.02595-13">10.1128/JVI.02595-13</a>.
  short: D. Kuchibhatla, W. Sherman, B. Chung, S. Cook, G. Schneider, B. Eisenhaber,
    D. Karlin, Journal of Virology 88 (2014) 10–20.
date_created: 2018-12-11T11:56:34Z
date_published: 2014-01-01T00:00:00Z
date_updated: 2021-01-12T06:56:17Z
day: '01'
ddc:
- '570'
department:
- _id: MD
doi: 10.1128/JVI.02595-13
file:
- access_level: open_access
  checksum: 2c121b5e884992dfec5605bdf4e659da
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:13:43Z
  date_updated: 2020-07-14T12:45:34Z
  file_id: '5029'
  file_name: IST-2016-417-v1+1_J._Virol.-2014-Kuchibhatla-10-20.pdf
  file_size: 825756
  relation: main_file
file_date_updated: 2020-07-14T12:45:34Z
has_accepted_license: '1'
intvolume: '        88'
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 10 - 20
publication: Journal of Virology
publication_identifier:
  issn:
  - 0022538X
publication_status: published
publisher: ASM
publist_id: '4698'
pubrep_id: '417'
quality_controlled: '1'
scopus_import: 1
status: public
title: Powerful sequence similarity search methods and in-depth manual analyses can
  identify remote homologs in many apparently "orphan" viral proteins
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 88
year: '2014'
...
---
_id: '2826'
abstract:
- lang: eng
  text: Myopia, or near-sightedness, is an ocular refractive error of unfocused image
    quality in front of the retinal plane. Individuals with high-grade myopia (dioptric
    power greater than -6.00) are predisposed to ocular morbidities such as glaucoma,
    retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is
    highly heritable, and to date multiple gene loci have been reported. We performed
    exome sequencing in 4 individuals from an 11-member family of European descent
    from the United States. Affected individuals had a mean dioptric spherical equivalent
    of -22.00 sphere. A premature stop codon mutation c.157C&gt;T (p.Gln53*) cosegregating
    with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent
    analyses identified three additional mutations in three highly myopic unrelated
    individuals (c.341G&gt;A, c.418G&gt;A, and c.776C&gt;T). To determine differential
    gene expression in a developmental mouse model, we induced myopia by applying
    a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated
    in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein
    localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for
    a copper homeostasis protein influential in mitochondrial cytochrome c oxidase
    activity. Copper deficiencies have been linked with photoreceptor loss and myopia
    with increased scleral wall elasticity. Retinal thinning has been reported with
    an SC02 variant. Human mutation identification with support from an induced myopic
    animal provides biological insights of myopic development.
author:
- first_name: Khanh
  full_name: Tran Viet, Khanh
  last_name: Tran Viet
- first_name: Caldwell
  full_name: Powell, Caldwell
  last_name: Powell
- first_name: Veluchamy
  full_name: Barathi, Veluchamy
  last_name: Barathi
- first_name: Thomas
  full_name: Klemm, Thomas
  last_name: Klemm
- first_name: Sebastian
  full_name: Maurer Stroh, Sebastian
  last_name: Maurer Stroh
- first_name: Vachiranee
  full_name: Limviphuvadh, Vachiranee
  last_name: Limviphuvadh
- first_name: Vincent
  full_name: Soler, Vincent
  last_name: Soler
- first_name: Candice
  full_name: Ho, Candice
  last_name: Ho
- first_name: Tammy
  full_name: Yanovitch, Tammy
  last_name: Yanovitch
- first_name: Georg
  full_name: Schneider, Georg
  id: 329095A0-F248-11E8-B48F-1D18A9856A87
  last_name: Schneider
- first_name: Yi
  full_name: Li, Yi
  last_name: Li
- first_name: Erica
  full_name: Nading, Erica
  last_name: Nading
- first_name: Ravikanth
  full_name: Metlapally, Ravikanth
  last_name: Metlapally
- first_name: Seang
  full_name: Saw, Seang
  last_name: Saw
- first_name: Liang
  full_name: Goh, Liang
  last_name: Goh
- first_name: Steve
  full_name: Rozen, Steve
  last_name: Rozen
- first_name: Terri
  full_name: Young, Terri
  last_name: Young
citation:
  ama: Tran Viet K, Powell C, Barathi V, et al. Mutations in SCO2 are associated with
    autosomal-dominant high-grade myopia. <i>American Journal of Human Genetics</i>.
    2013;92(5):820-826. doi:<a href="https://doi.org/10.1016/j.ajhg.2013.04.005">10.1016/j.ajhg.2013.04.005</a>
  apa: Tran Viet, K., Powell, C., Barathi, V., Klemm, T., Maurer Stroh, S., Limviphuvadh,
    V., … Young, T. (2013). Mutations in SCO2 are associated with autosomal-dominant
    high-grade myopia. <i>American Journal of Human Genetics</i>. Cell Press. <a href="https://doi.org/10.1016/j.ajhg.2013.04.005">https://doi.org/10.1016/j.ajhg.2013.04.005</a>
  chicago: Tran Viet, Khanh, Caldwell Powell, Veluchamy Barathi, Thomas Klemm, Sebastian
    Maurer Stroh, Vachiranee Limviphuvadh, Vincent Soler, et al. “Mutations in SCO2
    Are Associated with Autosomal-Dominant High-Grade Myopia.” <i>American Journal
    of Human Genetics</i>. Cell Press, 2013. <a href="https://doi.org/10.1016/j.ajhg.2013.04.005">https://doi.org/10.1016/j.ajhg.2013.04.005</a>.
  ieee: K. Tran Viet <i>et al.</i>, “Mutations in SCO2 are associated with autosomal-dominant
    high-grade myopia,” <i>American Journal of Human Genetics</i>, vol. 92, no. 5.
    Cell Press, pp. 820–826, 2013.
  ista: Tran Viet K, Powell C, Barathi V, Klemm T, Maurer Stroh S, Limviphuvadh V,
    Soler V, Ho C, Yanovitch T, Schneider G, Li Y, Nading E, Metlapally R, Saw S,
    Goh L, Rozen S, Young T. 2013. Mutations in SCO2 are associated with autosomal-dominant
    high-grade myopia. American Journal of Human Genetics. 92(5), 820–826.
  mla: Tran Viet, Khanh, et al. “Mutations in SCO2 Are Associated with Autosomal-Dominant
    High-Grade Myopia.” <i>American Journal of Human Genetics</i>, vol. 92, no. 5,
    Cell Press, 2013, pp. 820–26, doi:<a href="https://doi.org/10.1016/j.ajhg.2013.04.005">10.1016/j.ajhg.2013.04.005</a>.
  short: K. Tran Viet, C. Powell, V. Barathi, T. Klemm, S. Maurer Stroh, V. Limviphuvadh,
    V. Soler, C. Ho, T. Yanovitch, G. Schneider, Y. Li, E. Nading, R. Metlapally,
    S. Saw, L. Goh, S. Rozen, T. Young, American Journal of Human Genetics 92 (2013)
    820–826.
date_created: 2018-12-11T11:59:48Z
date_published: 2013-05-02T00:00:00Z
date_updated: 2021-01-12T06:59:59Z
day: '02'
department:
- _id: MD
doi: 10.1016/j.ajhg.2013.04.005
external_id:
  pmid:
  - '23643385'
intvolume: '        92'
issue: '5'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644634/
month: '05'
oa: 1
oa_version: Submitted Version
page: 820 - 826
pmid: 1
publication: American Journal of Human Genetics
publication_status: published
publisher: Cell Press
publist_id: '3974'
quality_controlled: '1'
scopus_import: 1
status: public
title: Mutations in SCO2 are associated with autosomal-dominant high-grade myopia
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 92
year: '2013'
...