Copy number variation analysis reveals additional variants contributing to endometriosis development.
OBJECTIVE
Endometriosis is a gynecological disease influenced by multiple genetic and environmental factors. The aim of the current study was to use SNP-array technology to identify genomic aberrations that may possibly contribute to the development of endometriosis.


METHODS
We performed an SNP-array genotyping of pooled DNA samples from both patients (n = 100) and controls (n = 50). Copy number variation (CNV) calling and association analyses were performed using PennCNV software. MLPA and TaqMan Copy-Number assays were used for validation of CNVs discovered.


RESULTS
We detected 49 CNV loci that were present in patients with endometriosis and absent in the control group. After validation procedures, we confirmed six CNV loci in the subtelomeric regions, including 1p36.33, 16p13.3, 19p13.3, and 20p13, representing gains, while 17q25.3 and 20q13.33 showed losses. Among the intrachromosomal regions, our results revealed duplication at 19q13.1 within the FCGBP gene (p = 0.007).


CONCLUSIONS
We identified CNVs previously associated with endometriosis, together with six suggestive novel loci possibly involved in this disease. The intergenic locus on chromosome 19q13.1 shows strong association with endometriosis and is under further functional investigation.
Collective Health Department, Division of Sexual and Reproductive Health Care and Population Genetics, Faculdade de Medicina do ABC, Santo André, SP, Brazil. mafraf@email.chop.edu.|Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. mafraf@email.chop.edu.
Fernanda
F
Mafra
Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Diego
D
Mazzotti
Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Renata
R
Pellegrino
Collective Health Department, Division of Sexual and Reproductive Health Care and Population Genetics, Faculdade de Medicina do ABC, Santo André, SP, Brazil.
Bianca
B
Bianco
Collective Health Department, Division of Sexual and Reproductive Health Care and Population Genetics, Faculdade de Medicina do ABC, Santo André, SP, Brazil.
Caio Parente
CP
Barbosa
Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Hakon
H
Hakonarson
Collective Health Department, Division of Sexual and Reproductive Health Care and Population Genetics, Faculdade de Medicina do ABC, Santo André, SP, Brazil.
Denise
D
Christofolini
D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
Copy number variation; DNA pooling; Endometriosis; Infertility; SNP array