The genetic causes of male infertility
Grant number: 1120356 | Funding period: 2020 - 2021
6% of Australian men are infertile. Of these cases 50% are thought to be genetic in origin. Within this project we will replicate high-confidence genetic variants associated with human male infertility in the mouse. Doing so will allow the assignment of definitive genotype-phenotype correlations and the formulation of high confidence advice for clinicians and patients. It will also provide a means to define the mechanism of action and the tools for future pro-fertility treatments.
Related publications (12)
Diverse monogenic subforms of human spermatogenic failure.
Liina Nagirnaja, Alexandra M Lopes, Wu-Lin Charng, Brian Miller, Rytis Stakaitis, Ieva Golubickaite, Alexandra Stendahl, Tianpengcheng Luan, Corinna Friedrich, Eisa Mahyari, Eloise Fadial, Laura Kasak, Katinka Vigh-Conrad, Manon S Oud, Miguel J Xavier, Samuel R Cheers, Emma R James, Jingtao Guo, Timothy G Jenkins, Antoni Riera-Escamilla
Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis ..
Zinc finger RNA binding protein 2 (ZFR2) is not required for male fertility in the mouse
Lachlan M Cauchi, Brendan J Houston, Liina Nagirnaja, Anne E O'Connor, D Jo Merriner, Kenneth Aston, Peter N Schlegel, Don F Conrad, Richard Burke, Moira K O'Bryan
BACKGROUND: Thousands of genes are expressed during spermatogenesis and male infertility has a strong genetic component. Within th..
DDB1-and CUL4-associated factor 12-like protein 1 (Dcaf12l1) is not essential for male fertility in mice
Brendan J Houston, Alexandra M Lopes, Maris Laan, Liina Nagirnaja, Anne E O'Connor, D Jo Merriner, Joseph Nguyen, Margus Punab, Antoni Riera-Escamilla, Csilla Krausz, Kenneth Ivan Aston, Donald F Conrad, Moira K O'Bryan
Male infertility is a common condition affecting at least 7% of men worldwide and is often genetic in origin. Using whole exome se..
Actionable secondary findings following exome sequencing of 836 non-obstructive azoospermia cases and their value in patient management
Laura Kasak, Kristiina Lillepea, Liina Nagirnaja, Kenneth Aston, Peter N Schlegel, Joao Goncalves, Filipa Carvalho, Daniel Moreno-Mendoza, Kristian Almstrup, Michael L Eisenberg, Keith A Jarvi, Moira K O'Bryan, Alexandra M Lopes, Donald F Conrad, Margus Punab, Maris Laan
STUDY QUESTION: What is the load, distribution and added clinical value of secondary findings (SFs) identified in exome sequencing..
Human INHBB Gene Variant (c.1079T>C:p.Met360Thr) Alters Testis Germ Cell Content, but Does Not Impact Fertility in Mice
Brendan J Houston, Anne E O'Connor, Degang Wang, Georgia Goodchild, D Jo Merriner, Haitong Luan, Don F Conrad, Liina Nagirnaja, Kenneth Aston, Sabine Kliesch, Margot J Wyrwoll, Corinna Friedrich, Frank Tuettelmann, Craig Harrison, Moira K O'Bryan, Kelly Walton
Testicular-derived inhibin B (α/β B dimers) acts in an endocrine manner to suppress pituitary production of follicle-stimulating h..
A de novo paradigm for male infertility.
MS Oud, RM Smits, HE Smith, FK Mastrorosa, GS Holt, BJ Houston, PF de Vries, BKS Alobaidi, LE Batty, H Ismail, J Greenwood, H Sheth, A Mikulasova, GDN Astuti, C Gilissen, K McEleny, H Turner, J Coxhead, S Cockell, DDM Braat
De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutat..
A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships
Brendan J Houston, Antoni Riera-Escamilla, Margot J Wyrwoll, Albert Salas-Huetos, Miguel J Xavier, Liina Nagirnaja, Corinna Friedrich, Don F Conrad, Kenneth Aston, Csilla Krausz, Frank Tuttelmann, Moira K O'Bryan, Joris A Veltman, Manon S Oud
BACKGROUND: Human male infertility has a notable genetic component, including well-established diagnoses such as Klinefelter syndr..
Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility
Chunyu Liu, Chaofeng Tu, Lingbo Wang, Huan Wu, Brendan J Houston, Francesco K Mastrorosa, Wen Zhang, Ying Shen, Jiaxiong Wang, Shixiong Tian, Lanlan Meng, Jiangshan Cong, Shenmin Yang, Yiwen Jiang, Shuyan Tang, Yuyan Zeng, Mingrong Lv, Ge Lin, Jinsong Li, Hexige Saiyin
Asthenoteratozoospermia characterized by multiple morphological abnormalities of the flagella (MMAF) has been identified as a sub-..
The Sertoli cell expressed gene secernin-1 (Scrn1) is dispensable for male fertility in the mouse
Brendan J Houston, Liina Nagirnaja, D Jo Merriner, Anne E O'Connor, Hidenobu Okuda, Kenan Omurtag, Craig Smith, Kenneth I Aston, Donald F Conrad, Moira K O'Bryan
BACKGROUND: Male infertility is a prevalent clinical presentation for which there is likely a strong genetic component due to the ..
Programmed Cell Death 2-Like (Pdcd2l) Is Required for Mouse Embryonic Development
Brendan J Houston, Manon S Oud, Daniel M Aguirre, D Jo Merriner, Anne E O'Connor, Ozlem Okutman, Stephane Viville, Richard Burke, Joris A Veltman, Moira K O'Bryan
Globozoospermia is a rare form of male infertility where men produce round-headed sperm that are incapable of fertilizing an oocyt..
Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia
MS Oud, O Okutman, LAJ Hendricks, PF de Vries, BJ Houston, LELM Vissers, MK O'Bryan, L Ramos, HE Chemes, S Viville, JA Veltman
STUDY QUESTION: Can exome sequencing identify new genetic causes of globozoospermia? SUMMARY ANSWER: Exome sequencing in 15 cases ..