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Genetics of mammalian meiosis
Published in C. Yan Cheng, Spermatogenesis, 2018
Genetic studies in mouse and other model organisms have identified many meiosis-specific proteins discussed here and elucidated the molecular mechanisms underlying their functions. These functional studies provide a strong rationale for genetic studies in humans. Mutations in meiosis-specific genes are expected to be causes of human infertility. To date, human genetic studies have identified causative mutations in nine meiosis-specific genes (Table 8.2). These mutations cause either azoospermia in men or premature ovarian failure in women. Most of these mutations were found in the offspring of consanguineous marriage and identified by exome sequencing of affected individuals. Homozygous mutations in MEIOB, PSMC3IP, STAG3, SYCE1, TEX14, and TEX15 were identified in the offspring of consanguineous couples (Table 8.2). Sequencing of sporadic cases of infertile men reveals that mutations in TEX11, an X-linked meiosis-specific gene, cause infertility in ~1% of nonobstructive azoospermia.90,117 In the era of precision medicine, future genomic sequencing of infertile patients is expected to identify causative mutations in more meiosis-specific genes. Such information will be valuable for diagnosis and genetic counseling in the treatment of infertility in the upcoming era of precision medicine.
A systematic review on the genetics of male infertility in the era of next-generation sequencing
Published in Arab Journal of Urology, 2018
Amal Robay, Saleha Abbasi, Ammira Akil, Haitham El-Bardisi, Mohamed Arafa, Ronald G. Crystal, Khalid A. Fakhro
Maor-Sagie et al. [28] used whole-exome sequencing in a single patient with NOA to find a candidate homozygous splice-site mutation in synaptonemal complex central element protein 1 (SYCE1), which was then discovered to segregate with the disease in the family, i.e., one affected brother shared the same homozygous mutation, but it was absent from the fertile siblings and in heterozygous state in carrier parents, who were consanguineous. Okutman et al. [29] discovered a recessive mutation in testis expressed 15, meiosis and synapsis associated (TEX15) segregating with NOA in three affected siblings in a Turkish family, absent from the fertile brother and parents. Ramasamy et al. [30] discovered neuronal PAS domain protein 2 (NPAS2) mutations in three siblings with azoospermia in another consanguineous family from Turkey. Finally, Gershoni et al. [31] used a combination of whole-exome sequencing and whole-genome sequencing in different families to discover mutations in the genes: meiosis specific with OB domains (MEIOB), testis expressed 14, intercellular bridge forming factor (TEX14) and dynein axonemal heavy chain 6 (DNAH6) [31]. In all cases, the mutations segregated with the affected members within each family and were rare in control databases, making them prime candidates for causing disease [31].