A rare synaptonemal complex protein 3 gene variant in unexplained female infertility

S. Nishiyama, T. Kishi, Takema Kato, M. Suzuki, H. Bolor, Haruki Nishizawa, Nakao Iwata, Y. Udagawa, Hiroki Kurahashi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Synaptonemal complex protein 3 (SYCP3) plays a critical role in homologous chromosome pairing and recombination in meiosis, and mice deficient in this gene show infertility in males and subfertility in females. The aim of our current study was to determine whether genetic alterations in the SYCP3 gene are associated with female infertility in humans. We examined sequence variations of the SYCP3 gene in genomic DNA from 88 Japanese women with unexplained infertility and 165 samples obtained from a fertile control group. Case-control study using seven tagging single nucleotide polymorphisms revealed no significant association between common SYCP3 variants and unexplained infertility. However, only infertile women were homozygous for the minor allele of a novel rare variant in the coding region, c.666A>G (222Q>Q). The minor allele frequency was significantly higher in the infertile cohort (P < 0.05). This variant is predicted to create a cryptic splice site, although the expression of a mini-gene harboring the variant in HeLa cells or mouse testis did not demonstrate any effects on gene splicing. Our current findings therefore suggest that the c.666A>G variant in the SYCP3 gene might possibly contribute to female infertility in humans, although larger studies are needed to assess the possible effects of SYCP3 gene variation on human female infertility.

Original languageEnglish
Pages (from-to)266-271
Number of pages6
JournalMolecular Human Reproduction
Volume17
Issue number4
DOIs
Publication statusPublished - 01-04-2011

Fingerprint

Synaptonemal Complex
Female Infertility
Infertility
Proteins
Chromosome Pairing
Male Infertility
Meiosis
Gene Frequency
Genetic Recombination
Single Nucleotide Polymorphism
Case-Control Studies
Alleles
Control Groups
DNA
Genes

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Embryology
  • Molecular Biology
  • Genetics
  • Obstetrics and Gynaecology
  • Developmental Biology
  • Cell Biology

Cite this

@article{b0b93efac24f4ac78bd365f2ab2399b3,
title = "A rare synaptonemal complex protein 3 gene variant in unexplained female infertility",
abstract = "Synaptonemal complex protein 3 (SYCP3) plays a critical role in homologous chromosome pairing and recombination in meiosis, and mice deficient in this gene show infertility in males and subfertility in females. The aim of our current study was to determine whether genetic alterations in the SYCP3 gene are associated with female infertility in humans. We examined sequence variations of the SYCP3 gene in genomic DNA from 88 Japanese women with unexplained infertility and 165 samples obtained from a fertile control group. Case-control study using seven tagging single nucleotide polymorphisms revealed no significant association between common SYCP3 variants and unexplained infertility. However, only infertile women were homozygous for the minor allele of a novel rare variant in the coding region, c.666A>G (222Q>Q). The minor allele frequency was significantly higher in the infertile cohort (P < 0.05). This variant is predicted to create a cryptic splice site, although the expression of a mini-gene harboring the variant in HeLa cells or mouse testis did not demonstrate any effects on gene splicing. Our current findings therefore suggest that the c.666A>G variant in the SYCP3 gene might possibly contribute to female infertility in humans, although larger studies are needed to assess the possible effects of SYCP3 gene variation on human female infertility.",
author = "S. Nishiyama and T. Kishi and Takema Kato and M. Suzuki and H. Bolor and Haruki Nishizawa and Nakao Iwata and Y. Udagawa and Hiroki Kurahashi",
year = "2011",
month = "4",
day = "1",
doi = "10.1093/molehr/gaq098",
language = "English",
volume = "17",
pages = "266--271",
journal = "Molecular Human Reproduction",
issn = "1360-9947",
publisher = "Oxford University Press",
number = "4",

}

A rare synaptonemal complex protein 3 gene variant in unexplained female infertility. / Nishiyama, S.; Kishi, T.; Kato, Takema; Suzuki, M.; Bolor, H.; Nishizawa, Haruki; Iwata, Nakao; Udagawa, Y.; Kurahashi, Hiroki.

In: Molecular Human Reproduction, Vol. 17, No. 4, 01.04.2011, p. 266-271.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A rare synaptonemal complex protein 3 gene variant in unexplained female infertility

AU - Nishiyama, S.

AU - Kishi, T.

AU - Kato, Takema

AU - Suzuki, M.

AU - Bolor, H.

AU - Nishizawa, Haruki

AU - Iwata, Nakao

AU - Udagawa, Y.

AU - Kurahashi, Hiroki

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Synaptonemal complex protein 3 (SYCP3) plays a critical role in homologous chromosome pairing and recombination in meiosis, and mice deficient in this gene show infertility in males and subfertility in females. The aim of our current study was to determine whether genetic alterations in the SYCP3 gene are associated with female infertility in humans. We examined sequence variations of the SYCP3 gene in genomic DNA from 88 Japanese women with unexplained infertility and 165 samples obtained from a fertile control group. Case-control study using seven tagging single nucleotide polymorphisms revealed no significant association between common SYCP3 variants and unexplained infertility. However, only infertile women were homozygous for the minor allele of a novel rare variant in the coding region, c.666A>G (222Q>Q). The minor allele frequency was significantly higher in the infertile cohort (P < 0.05). This variant is predicted to create a cryptic splice site, although the expression of a mini-gene harboring the variant in HeLa cells or mouse testis did not demonstrate any effects on gene splicing. Our current findings therefore suggest that the c.666A>G variant in the SYCP3 gene might possibly contribute to female infertility in humans, although larger studies are needed to assess the possible effects of SYCP3 gene variation on human female infertility.

AB - Synaptonemal complex protein 3 (SYCP3) plays a critical role in homologous chromosome pairing and recombination in meiosis, and mice deficient in this gene show infertility in males and subfertility in females. The aim of our current study was to determine whether genetic alterations in the SYCP3 gene are associated with female infertility in humans. We examined sequence variations of the SYCP3 gene in genomic DNA from 88 Japanese women with unexplained infertility and 165 samples obtained from a fertile control group. Case-control study using seven tagging single nucleotide polymorphisms revealed no significant association between common SYCP3 variants and unexplained infertility. However, only infertile women were homozygous for the minor allele of a novel rare variant in the coding region, c.666A>G (222Q>Q). The minor allele frequency was significantly higher in the infertile cohort (P < 0.05). This variant is predicted to create a cryptic splice site, although the expression of a mini-gene harboring the variant in HeLa cells or mouse testis did not demonstrate any effects on gene splicing. Our current findings therefore suggest that the c.666A>G variant in the SYCP3 gene might possibly contribute to female infertility in humans, although larger studies are needed to assess the possible effects of SYCP3 gene variation on human female infertility.

UR - http://www.scopus.com/inward/record.url?scp=79952611507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952611507&partnerID=8YFLogxK

U2 - 10.1093/molehr/gaq098

DO - 10.1093/molehr/gaq098

M3 - Article

C2 - 21159741

AN - SCOPUS:79952611507

VL - 17

SP - 266

EP - 271

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

SN - 1360-9947

IS - 4

ER -