Evolutionarily assembled cis-regulatory module at a human ciliopathy locus

Jeong Ho Lee, Jennifer L. Silhavy, Ji Eun Lee, Lihadh Al-Gazali, Sophie Thomas, Erica E. Davis, Stephanie L. Bielas, Kiley J. Hill, Miriam Iannicelli, Francesco Brancati, Stacey B. Gabriel, Carsten Russ, Clare V. Logan, Saghira Malik Sharif, Christopher P. Bennett, Masumi Abe, Friedhelm Hildebrandt, Bill H. Diplas, Tania Attié-Bitach, Nicholas KatsanisAnna Rajab, Roshan Koul, Laszlo Sztriha, Elizabeth R. Waters, Susan Ferro-Novick, C. Geoffrey Woods, Colin A. Johnson, Enza Maria Valente, Maha S. Zaki, Joseph G. Gleeson

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.

Original languageEnglish
Pages (from-to)966-969
Number of pages4
JournalScience
Volume335
Issue number6071
DOIs
Publication statusPublished - Feb 24 2012

Fingerprint

Genes
Intergenic DNA
Reptiles
Cilia
Amphibians
Multigene Family
Sequence Homology
Vertebrates
Mammals
Ciliopathies
Gene Expression
Mutation
Joubert syndrome 1

ASJC Scopus subject areas

  • General

Cite this

Lee, J. H., Silhavy, J. L., Lee, J. E., Al-Gazali, L., Thomas, S., Davis, E. E., ... Gleeson, J. G. (2012). Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science, 335(6071), 966-969. https://doi.org/10.1126/science.1213506

Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. / Lee, Jeong Ho; Silhavy, Jennifer L.; Lee, Ji Eun; Al-Gazali, Lihadh; Thomas, Sophie; Davis, Erica E.; Bielas, Stephanie L.; Hill, Kiley J.; Iannicelli, Miriam; Brancati, Francesco; Gabriel, Stacey B.; Russ, Carsten; Logan, Clare V.; Sharif, Saghira Malik; Bennett, Christopher P.; Abe, Masumi; Hildebrandt, Friedhelm; Diplas, Bill H.; Attié-Bitach, Tania; Katsanis, Nicholas; Rajab, Anna; Koul, Roshan; Sztriha, Laszlo; Waters, Elizabeth R.; Ferro-Novick, Susan; Woods, C. Geoffrey; Johnson, Colin A.; Valente, Enza Maria; Zaki, Maha S.; Gleeson, Joseph G.

In: Science, Vol. 335, No. 6071, 24.02.2012, p. 966-969.

Research output: Contribution to journalArticle

Lee, JH, Silhavy, JL, Lee, JE, Al-Gazali, L, Thomas, S, Davis, EE, Bielas, SL, Hill, KJ, Iannicelli, M, Brancati, F, Gabriel, SB, Russ, C, Logan, CV, Sharif, SM, Bennett, CP, Abe, M, Hildebrandt, F, Diplas, BH, Attié-Bitach, T, Katsanis, N, Rajab, A, Koul, R, Sztriha, L, Waters, ER, Ferro-Novick, S, Woods, CG, Johnson, CA, Valente, EM, Zaki, MS & Gleeson, JG 2012, 'Evolutionarily assembled cis-regulatory module at a human ciliopathy locus', Science, vol. 335, no. 6071, pp. 966-969. https://doi.org/10.1126/science.1213506
Lee JH, Silhavy JL, Lee JE, Al-Gazali L, Thomas S, Davis EE et al. Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science. 2012 Feb 24;335(6071):966-969. https://doi.org/10.1126/science.1213506
Lee, Jeong Ho ; Silhavy, Jennifer L. ; Lee, Ji Eun ; Al-Gazali, Lihadh ; Thomas, Sophie ; Davis, Erica E. ; Bielas, Stephanie L. ; Hill, Kiley J. ; Iannicelli, Miriam ; Brancati, Francesco ; Gabriel, Stacey B. ; Russ, Carsten ; Logan, Clare V. ; Sharif, Saghira Malik ; Bennett, Christopher P. ; Abe, Masumi ; Hildebrandt, Friedhelm ; Diplas, Bill H. ; Attié-Bitach, Tania ; Katsanis, Nicholas ; Rajab, Anna ; Koul, Roshan ; Sztriha, Laszlo ; Waters, Elizabeth R. ; Ferro-Novick, Susan ; Woods, C. Geoffrey ; Johnson, Colin A. ; Valente, Enza Maria ; Zaki, Maha S. ; Gleeson, Joseph G. / Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. In: Science. 2012 ; Vol. 335, No. 6071. pp. 966-969.
@article{20522d42c5874b1fb09bd47af52fb088,
title = "Evolutionarily assembled cis-regulatory module at a human ciliopathy locus",
abstract = "Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.",
author = "Lee, {Jeong Ho} and Silhavy, {Jennifer L.} and Lee, {Ji Eun} and Lihadh Al-Gazali and Sophie Thomas and Davis, {Erica E.} and Bielas, {Stephanie L.} and Hill, {Kiley J.} and Miriam Iannicelli and Francesco Brancati and Gabriel, {Stacey B.} and Carsten Russ and Logan, {Clare V.} and Sharif, {Saghira Malik} and Bennett, {Christopher P.} and Masumi Abe and Friedhelm Hildebrandt and Diplas, {Bill H.} and Tania Atti{\'e}-Bitach and Nicholas Katsanis and Anna Rajab and Roshan Koul and Laszlo Sztriha and Waters, {Elizabeth R.} and Susan Ferro-Novick and Woods, {C. Geoffrey} and Johnson, {Colin A.} and Valente, {Enza Maria} and Zaki, {Maha S.} and Gleeson, {Joseph G.}",
year = "2012",
month = "2",
day = "24",
doi = "10.1126/science.1213506",
language = "English",
volume = "335",
pages = "966--969",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6071",

}

TY - JOUR

T1 - Evolutionarily assembled cis-regulatory module at a human ciliopathy locus

AU - Lee, Jeong Ho

AU - Silhavy, Jennifer L.

AU - Lee, Ji Eun

AU - Al-Gazali, Lihadh

AU - Thomas, Sophie

AU - Davis, Erica E.

AU - Bielas, Stephanie L.

AU - Hill, Kiley J.

AU - Iannicelli, Miriam

AU - Brancati, Francesco

AU - Gabriel, Stacey B.

AU - Russ, Carsten

AU - Logan, Clare V.

AU - Sharif, Saghira Malik

AU - Bennett, Christopher P.

AU - Abe, Masumi

AU - Hildebrandt, Friedhelm

AU - Diplas, Bill H.

AU - Attié-Bitach, Tania

AU - Katsanis, Nicholas

AU - Rajab, Anna

AU - Koul, Roshan

AU - Sztriha, Laszlo

AU - Waters, Elizabeth R.

AU - Ferro-Novick, Susan

AU - Woods, C. Geoffrey

AU - Johnson, Colin A.

AU - Valente, Enza Maria

AU - Zaki, Maha S.

AU - Gleeson, Joseph G.

PY - 2012/2/24

Y1 - 2012/2/24

N2 - Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.

AB - Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.

UR - http://www.scopus.com/inward/record.url?scp=84862776586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862776586&partnerID=8YFLogxK

U2 - 10.1126/science.1213506

DO - 10.1126/science.1213506

M3 - Article

C2 - 22282472

AN - SCOPUS:84862776586

VL - 335

SP - 966

EP - 969

JO - Science

JF - Science

SN - 0036-8075

IS - 6071

ER -