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.
OBJECTIVE
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.


CONCLUSIONS
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.
Bruce
Heather A
HA
Departments of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sachs
Nancy
N
Rudnicki
Dobrila D
DD
Lin
Stephanie G
SG
Willour
Virginia L
VL
Cowell
John K
JK
Conroy
Jeffrey
J
McQuaid
Devin E
DE
Rossi
Michael
M
Gaile
Daniel P
DP
Nowak
Norma J
NJ
Holmes
Susan E
SE
Sklar
Pamela
P
Ross
Christopher A
CA
Delisi
Lynn E
LE
Margolis
Russell L
RL
D000483:Alleles; D016022:Case-Control Studies; D020090:Chromosome Segregation; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics*