OBJECTIVES: Genomic copy number variations (CNVs) are a major form of variation in the human genome and play an etiologic role in several neuropsychiatric diseases. Tandem repeats, particularly with long (>50 bp) repeat units, are a relatively common yet underexplored type of CNV that may significantly contribute to human genomic variation and disease risk. We therefore carried out a pilot experiment to explore the potential role of long tandem repeats as risk factors in psychiatric disorders. METHODS: A bacterial artificial chromosome-based array comparative genomic hybridization (aCGH) platform was used to examine CNVs in genomic DNA from 34 probands with schizophrenia or schizoaffective disorder. RESULTS: The aCGH screen detected an apparent deletion on 5p15.1 in two probands, caused by the presence in each proband of two low copy number (short) alleles of a tandem repeat that ranges in length from fewer than 10 to greater than 50 3.4 kb units in the population examined. Short alleles partially segregate with schizophrenia in a small number of families, though linkage was not significant. An association study showed no significant difference in repeat length between 406 schizophrenia cases and 392 controls. CONCLUSION: Although we did not demonstrate a relationship between the 5p15.1 repeat and schizophrenia, our results illustrate that long tandem repeats represent an intriguing type of genetic variation that have not been studied in earlier connection with psychiatric illness. aCGH can detect a small subset of these repeats, but systematic investigation will require the development of specific arrays and improved analytical methods.
OBJECTIVES: Genomic copy number variations (CNVs) are a major form of variation in the human genome and play an etiologic role in several neuropsychiatric diseases. Tandem repeats, particularly with long (>50 bp) repeat units, are a relatively common yet underexplored type of CNV that may significantly contribute to human genomic variation and disease risk. We therefore carried out a pilot experiment to explore the potential role of long tandem repeats as risk factors in psychiatric disorders. METHODS: A bacterial artificial chromosome-based array comparative genomic hybridization (aCGH) platform was used to examine CNVs in genomic DNA from 34 probands with schizophrenia or schizoaffective disorder. RESULTS: The aCGH screen detected an apparent deletion on 5p15.1 in two probands, caused by the presence in each proband of two low copy number (short) alleles of a tandem repeat that ranges in length from fewer than 10 to greater than 50 3.4 kb units in the population examined. Short alleles partially segregate with schizophrenia in a small number of families, though linkage was not significant. An association study showed no significant difference in repeat length between 406 schizophrenia cases and 392 controls. CONCLUSION: Although we did not demonstrate a relationship between the 5p15.1 repeat and schizophrenia, our results illustrate that long tandem repeats represent an intriguing type of genetic variation that have not been studied in earlier connection with psychiatric illness. aCGH can detect a small subset of these repeats, but systematic investigation will require the development of specific arrays and improved analytical methods.
Authors: Lynn E DeLisi; Sarah H Shaw; Timothy J Crow; Gail Shields; Angela B Smith; Veronica W Larach; Nigel Wellman; Josephine Loftus; Betsy Nanthakumar; Kamran Razi; John Stewart; Margherita Comazzi; Antonio Vita; Thomas Heffner; Robin Sherrington Journal: Am J Psychiatry Date: 2002-05 Impact factor: 18.112
Authors: W James Kent; Charles W Sugnet; Terrence S Furey; Krishna M Roskin; Tom H Pringle; Alan M Zahler; David Haussler Journal: Genome Res Date: 2002-06 Impact factor: 9.043
Authors: Andrew J Sharp; Sierra Hansen; Rebecca R Selzer; Ze Cheng; Regina Regan; Jane A Hurst; Helen Stewart; Sue M Price; Edward Blair; Raoul C Hennekam; Carrie A Fitzpatrick; Rick Segraves; Todd A Richmond; Cheryl Guiver; Donna G Albertson; Daniel Pinkel; Peggy S Eis; Stuart Schwartz; Samantha J L Knight; Evan E Eichler Journal: Nat Genet Date: 2006-08-13 Impact factor: 38.330
Authors: A E Pulver; G Nestadt; R Goldberg; R J Shprintzen; M Lamacz; P S Wolyniec; B Morrow; M Karayiorgou; S E Antonarakis; D Housman Journal: J Nerv Ment Dis Date: 1994-08 Impact factor: 2.254
Authors: Richard J L F Lemmers; Marielle Wohlgemuth; Kristiaan J van der Gaag; Patrick J van der Vliet; Corrie M M van Teijlingen; Peter de Knijff; George W Padberg; Rune R Frants; Silvere M van der Maarel Journal: Am J Hum Genet Date: 2007-09-07 Impact factor: 11.025
Authors: Jonathan Sebat; B Lakshmi; Dheeraj Malhotra; Jennifer Troge; Christa Lese-Martin; Tom Walsh; Boris Yamrom; Seungtai Yoon; Alex Krasnitz; Jude Kendall; Anthony Leotta; Deepa Pai; Ray Zhang; Yoon-Ha Lee; James Hicks; Sarah J Spence; Annette T Lee; Kaija Puura; Terho Lehtimäki; David Ledbetter; Peter K Gregersen; Joel Bregman; James S Sutcliffe; Vaidehi Jobanputra; Wendy Chung; Dorothy Warburton; Mary-Claire King; David Skuse; Daniel H Geschwind; T Conrad Gilliam; Kenny Ye; Michael Wigler Journal: Science Date: 2007-03-15 Impact factor: 47.728
Authors: Hreinn Stefansson; Dan Rujescu; Sven Cichon; Olli P H Pietiläinen; Andres Ingason; Stacy Steinberg; Ragnheidur Fossdal; Engilbert Sigurdsson; Thordur Sigmundsson; Jacobine E Buizer-Voskamp; Thomas Hansen; Klaus D Jakobsen; Pierandrea Muglia; Clyde Francks; Paul M Matthews; Arnaldur Gylfason; Bjarni V Halldorsson; Daniel Gudbjartsson; Thorgeir E Thorgeirsson; Asgeir Sigurdsson; Adalbjorg Jonasdottir; Aslaug Jonasdottir; Asgeir Bjornsson; Sigurborg Mattiasdottir; Thorarinn Blondal; Magnus Haraldsson; Brynja B Magnusdottir; Ina Giegling; Hans-Jürgen Möller; Annette Hartmann; Kevin V Shianna; Dongliang Ge; Anna C Need; Caroline Crombie; Gillian Fraser; Nicholas Walker; Jouko Lonnqvist; Jaana Suvisaari; Annamarie Tuulio-Henriksson; Tiina Paunio; Timi Toulopoulou; Elvira Bramon; Marta Di Forti; Robin Murray; Mirella Ruggeri; Evangelos Vassos; Sarah Tosato; Muriel Walshe; Tao Li; Catalina Vasilescu; Thomas W Mühleisen; August G Wang; Henrik Ullum; Srdjan Djurovic; Ingrid Melle; Jes Olesen; Lambertus A Kiemeney; Barbara Franke; Chiara Sabatti; Nelson B Freimer; Jeffrey R Gulcher; Unnur Thorsteinsdottir; Augustine Kong; Ole A Andreassen; Roel A Ophoff; Alexander Georgi; Marcella Rietschel; Thomas Werge; Hannes Petursson; David B Goldstein; Markus M Nöthen; Leena Peltonen; David A Collier; David St Clair; Kari Stefansson Journal: Nature Date: 2008-09-11 Impact factor: 49.962
Authors: Judit Balog; Dan Miller; Elena Sanchez-Curtailles; Jose Carbo-Marques; Gregory Block; Marco Potman; Peter de Knijff; Richard J L F Lemmers; Stephen J Tapscott; Silvère M van der Maarel Journal: Eur J Hum Genet Date: 2011-08-03 Impact factor: 4.246
Authors: David B Goldstein; Andrew Allen; Jonathan Keebler; Elliott H Margulies; Steven Petrou; Slavé Petrovski; Shamil Sunyaev Journal: Nat Rev Genet Date: 2013-06-11 Impact factor: 53.242
Authors: Andrea H Horakova; Shawn C Moseley; Christine R McLaughlin; Deanna C Tremblay; Brian P Chadwick Journal: Hum Mol Genet Date: 2012-07-12 Impact factor: 6.150
Authors: Mireille Schaap; Richard J L F Lemmers; Roel Maassen; Patrick J van der Vliet; Lennart F Hoogerheide; Herman K van Dijk; Nalan Baştürk; Peter de Knijff; Silvère M van der Maarel Journal: BMC Genomics Date: 2013-03-04 Impact factor: 3.969
Authors: Andrea H Horakova; J Mauro Calabrese; Christine R McLaughlin; Deanna C Tremblay; Terry Magnuson; Brian P Chadwick Journal: Genome Biol Date: 2012-08-20 Impact factor: 13.583