Long tandem repeats as a form of genomic copy number variation: Structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populations

Heather A. Bruce, Nancy Sachs, Dobrila D. Rudnicki, Stephanie G.Lin, Virginia L. Willour, John Kenneth Cowell, Jeffrey Conroy, Devin E. McQuaid, Michael Rossi, Daniel P. Gaile, Norma J. Nowak, Susan E. Holmes, Pamela Sklar, Christopher A. Ross, Lynn E. Delisi, Russell L. Margolis

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 (>50bp) 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.

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalPsychiatric Genetics
Volume19
Issue number2
DOIs
StatePublished - Apr 1 2009

Fingerprint

Tandem Repeat Sequences
Comparative Genomic Hybridization
Schizophrenia
Chromosomes
Population
Psychiatry
Alleles
Bacterial Artificial Chromosomes
Human Genome
Psychotic Disorders
DNA

Keywords

  • Array comparative genomic hybridization
  • Copy number variant
  • Deletion
  • Duplication
  • Megasatellite
  • Polymorphism
  • Psychosis
  • Repeat
  • Schizophrenia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Long tandem repeats as a form of genomic copy number variation : Structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populations. / Bruce, Heather A.; Sachs, Nancy; Rudnicki, Dobrila D.; G.Lin, Stephanie; Willour, Virginia L.; Cowell, John Kenneth; Conroy, Jeffrey; McQuaid, Devin E.; Rossi, Michael; Gaile, Daniel P.; Nowak, Norma J.; Holmes, Susan E.; Sklar, Pamela; Ross, Christopher A.; Delisi, Lynn E.; Margolis, Russell L.

In: Psychiatric Genetics, Vol. 19, No. 2, 01.04.2009, p. 64-71.

Research output: Contribution to journalArticle

Bruce, HA, Sachs, N, Rudnicki, DD, G.Lin, S, Willour, VL, Cowell, JK, Conroy, J, McQuaid, DE, Rossi, M, Gaile, DP, Nowak, NJ, Holmes, SE, Sklar, P, Ross, CA, Delisi, LE & Margolis, RL 2009, 'Long tandem repeats as a form of genomic copy number variation: Structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populations', Psychiatric Genetics, vol. 19, no. 2, pp. 64-71. https://doi.org/10.1097/YPG.0b013e3283207ff6
Bruce, Heather A. ; Sachs, Nancy ; Rudnicki, Dobrila D. ; G.Lin, Stephanie ; Willour, Virginia L. ; Cowell, John Kenneth ; Conroy, Jeffrey ; McQuaid, Devin E. ; Rossi, Michael ; Gaile, Daniel P. ; Nowak, Norma J. ; Holmes, Susan E. ; Sklar, Pamela ; Ross, Christopher A. ; Delisi, Lynn E. ; Margolis, Russell L. / Long tandem repeats as a form of genomic copy number variation : Structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populations. In: Psychiatric Genetics. 2009 ; Vol. 19, No. 2. pp. 64-71.
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abstract = "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 (>50bp) 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.",
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AU - G.Lin, Stephanie

AU - Willour, Virginia L.

AU - Cowell, John Kenneth

AU - Conroy, Jeffrey

AU - McQuaid, Devin E.

AU - Rossi, Michael

AU - Gaile, Daniel P.

AU - Nowak, Norma J.

AU - Holmes, Susan E.

AU - Sklar, Pamela

AU - Ross, Christopher A.

AU - Delisi, Lynn E.

AU - Margolis, Russell L.

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N2 - 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 (>50bp) 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.

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