SPACA3gene variants in a New Zealand cohort of infertile and fertile couples

SPRASA (also referred to as SLLP1) is a protein identified in the acrosome of human sperm and encoded by the gene SPACA3. SPRASA is associated with sperm-oocyte recognition and binding, and may play a role in fertility. In order to determine whether variants in the SPACA3 gene are associated with hu...

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Main Authors: Prendergast, Deborah, Woad, Kathryn J., Chamley, Lawrence W., Holland, Olivia J., Shelling, Andrew N.
Format: Article
Published: Taylor & Francis 2014
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Online Access:https://eprints.nottingham.ac.uk/46045/
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author Prendergast, Deborah
Woad, Kathryn J.
Chamley, Lawrence W.
Holland, Olivia J.
Shelling, Andrew N.
author_facet Prendergast, Deborah
Woad, Kathryn J.
Chamley, Lawrence W.
Holland, Olivia J.
Shelling, Andrew N.
author_sort Prendergast, Deborah
building Nottingham Research Data Repository
collection Online Access
description SPRASA (also referred to as SLLP1) is a protein identified in the acrosome of human sperm and encoded by the gene SPACA3. SPRASA is associated with sperm-oocyte recognition and binding, and may play a role in fertility. In order to determine whether variants in the SPACA3 gene are associated with human infertility, we undertook a genetic analysis of 102 infertile and 104 fertile couples. Three gene variants were identified using PCR-based DNA sequencing; 1) an insertion of TGC within a quadruple tri-nucleotide (TGC) repeat region in the 5’ untranslated region (UTR) (g.–22TGC(4_5), 2) a guanine to adenosine transition at position 239 (c.239G> A) resulting in a non-synonymous amino acid substitution from cysteine to tyrosine (p.C80Y) at position 80 in the putative transmembrane region, and 3) a novel nucleotide variant (c.691G> C) located in the 3’UTR. A functional effect of the g.–22TGC (4_5) was confirmed by a luciferase expression assay, while the effects of the variants c.239G> A and c.691G> C were predicted using in silico analysis. Although the frequencies of these variants were not significantly different between the infertile and fertile populations, we present evidence that the variants could affect the expression levels or function of SPRASA, thereby affecting a couple's fertility. Larger populations, especially individuals/couples with unexplained infertility, need to be screened for these variants to validate a relationship with fertility.
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spelling nottingham-460452020-05-04T16:47:33Z https://eprints.nottingham.ac.uk/46045/ SPACA3gene variants in a New Zealand cohort of infertile and fertile couples Prendergast, Deborah Woad, Kathryn J. Chamley, Lawrence W. Holland, Olivia J. Shelling, Andrew N. SPRASA (also referred to as SLLP1) is a protein identified in the acrosome of human sperm and encoded by the gene SPACA3. SPRASA is associated with sperm-oocyte recognition and binding, and may play a role in fertility. In order to determine whether variants in the SPACA3 gene are associated with human infertility, we undertook a genetic analysis of 102 infertile and 104 fertile couples. Three gene variants were identified using PCR-based DNA sequencing; 1) an insertion of TGC within a quadruple tri-nucleotide (TGC) repeat region in the 5’ untranslated region (UTR) (g.–22TGC(4_5), 2) a guanine to adenosine transition at position 239 (c.239G> A) resulting in a non-synonymous amino acid substitution from cysteine to tyrosine (p.C80Y) at position 80 in the putative transmembrane region, and 3) a novel nucleotide variant (c.691G> C) located in the 3’UTR. A functional effect of the g.–22TGC (4_5) was confirmed by a luciferase expression assay, while the effects of the variants c.239G> A and c.691G> C were predicted using in silico analysis. Although the frequencies of these variants were not significantly different between the infertile and fertile populations, we present evidence that the variants could affect the expression levels or function of SPRASA, thereby affecting a couple's fertility. Larger populations, especially individuals/couples with unexplained infertility, need to be screened for these variants to validate a relationship with fertility. Taylor & Francis 2014-05-28 Article PeerReviewed Prendergast, Deborah, Woad, Kathryn J., Chamley, Lawrence W., Holland, Olivia J. and Shelling, Andrew N. (2014) SPACA3gene variants in a New Zealand cohort of infertile and fertile couples. Human Fertility, 17 (2). pp. 106-113. ISSN 1464-7273 Reproduction gene mutation unexplained infertility http://www.tandfonline.com/doi/abs/10.3109/14647273.2014.907506?journalCode=ihuf20 doi:10.3109/14647273.2014.907506 doi:10.3109/14647273.2014.907506
spellingShingle Reproduction
gene mutation
unexplained infertility
Prendergast, Deborah
Woad, Kathryn J.
Chamley, Lawrence W.
Holland, Olivia J.
Shelling, Andrew N.
SPACA3gene variants in a New Zealand cohort of infertile and fertile couples
title SPACA3gene variants in a New Zealand cohort of infertile and fertile couples
title_full SPACA3gene variants in a New Zealand cohort of infertile and fertile couples
title_fullStr SPACA3gene variants in a New Zealand cohort of infertile and fertile couples
title_full_unstemmed SPACA3gene variants in a New Zealand cohort of infertile and fertile couples
title_short SPACA3gene variants in a New Zealand cohort of infertile and fertile couples
title_sort spaca3gene variants in a new zealand cohort of infertile and fertile couples
topic Reproduction
gene mutation
unexplained infertility
url https://eprints.nottingham.ac.uk/46045/
https://eprints.nottingham.ac.uk/46045/
https://eprints.nottingham.ac.uk/46045/