Sex chromosomes-linked single-gene disorders involved in human infertility

Jedidi, Inès; Ouchari, Mouna; Yin, Qinan

doi:10.1016/j.ejmg.2018.10.012

Cited by 12 publications

(10 citation statements)

References 147 publications

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“… 10 Mutations in this single X-linked gene cause infertility in 1% of azoospermic men. 10 20 27 Our study identified a TEX11 mutation in infertile patients with meiotic arrest, representing a 2.5% incidence. Our study therefore supports previously published data that it would be beneficial to include the TEX11 gene in genetic screening panels for the clinical evaluation of azoospermia patients.…”

Section: Discussionmentioning

confidence: 72%

A new TEX11 mutation causes azoospermia and testicular meiotic arrest

Yu¹,

Li²,

Cai

et al. 2021

Asian Journal of Andrology

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There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men. Here, we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del (p.D51fs) frame-shift mutation in exon 3 of the testis expressed 11 ( TEX11 ) gene in one patient. Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation. Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes. In contrast, testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression. Western blotting of human embryonic kidney (HEK293) cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression. In conclusion, we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient, emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.

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Section: Discussionmentioning

confidence: 72%

A new TEX11 mutation causes azoospermia and testicular meiotic arrest

Yu¹,

Li²,

Cai

et al. 2021

Asian Journal of Andrology

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“…Genes in these antagonizing regions include PO1FB, ZNF711, APOOL, HDX, DACH2, FAM133A, among others. These genes are associated with different disorders including infertility, reproductive deficiencies, primary ovarian failure [49][50][51]. When some of these genes are over-expressed, it can dysregulate the cristae morphology of the mammalian mitochondria [52].…”

Section: Discussionmentioning

confidence: 99%

Correlation scan: identifying genomic regions that affect genetic correlations applied to fertility traits

Olasege

Porto-Neto

Tahir

et al. 2021

Preprint

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Although the genetic correlation between complex traits have been estimated for more than a century, only recently we have started to map and understand the precise localization of the genomic region(s) that underpin these correlations. Reproductive traits are often genetically correlated, and yet we don’t fully understand the complexities, synergism, or trade-offs between male and female fertility. In this study, we used reproductive traits in two cattle populations to develop a novel framework termed correlation scan. This framework was used to identify regions associated with the genetic correlations between male and female fertility traits across the bovine genome. The traits used were age at first corpus luteum (AGECL) and serum levels of insulin growth hormone (IGF1 measured in bulls, IGF1b, or cows, IGF1c). The methodology developed herein used correlations of 500-SNP (single nucleotide polymorphism) effects in a 100-SNPs sliding window in each chromosome to identify regions in the genome that either drive (i.e., SNP effects on the same direction) or antagonize (i.e., SNP effects in the opposite direction) the genetic correlations between traits. We used a permutation test to confirm which regions of the genome harboured significant correlations. Hence, this framework can also identify neutral genomic regions with no effect on the pairwise trait studied. About 40% of the total genomic regions were identified as driving and antagonizing genetic correlations between male and female fertility traits in the two population. These regions confirmed the polygenic nature of the traits being studied and pointed to genes of interest. Quantitative trait loci (QTL) and functional enrichment analysis revealed that many significant windows co-located with known QTLs related to milk production and fertility traits, especially puberty. In general, the enriched reproductive QTLs driving the genetic correlations between male and female fertility are the same for both cattle populations, while the antagonizing regions were population specific. Moreover, most of the antagonizing regions were mapped to the chromosome X. These results suggest regions of the chromosome X for further investigation into the trade-offs between male and female fertility. Although the methodology was applied to cattle phenotypes, using high-density SNP genotypes, the general framework developed can be applied to any species or traits, and it can easily accommodate genome sequence data.Author summaryIn animal breeding, it is often common to estimate genetic correlations between economically important traits. These estimated correlations represent the average of the shared genetic similarities between traits across the genome. Despite this knowledge, we are yet to uncover the regions in the genome that explain the genetic correlations estimated. Targeting reproductive traits in cattle, we developed a new framework and used it to identify multiple regions across the genome that affect genetic correlations between male and female fertility traits. While some regions have no effect on these trait correlations, other loci drive or antagonize these relationships. We further subjected the identified regions to functional analysis and annotation for biological insights. Although the methodology was applied to cattle phenotypes, using high-density SNP genotypes, the general framework can be applied to any species or traits. For example, the method could be used to identify genomic regions that explain the interplay between various mental illness phenotypes in humans.

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“…The genetic conditions related to infertility, including the common and rare ones, account for almost 50% of all infertility causes [6,7]. In the presence of high suspicion of a genetically based infertility (such as malformations, recurrent abortions, and family history), according to the signs and symptoms observed by the specialist during the medical examination, a genetic test can provide a more accurate diagnosis of infertility and inform the couple about the risk of transmission of genetic defects to the offspring [8].…”

Section: Genetic Diseasesmentioning

confidence: 99%

“…The European Society of Human Genetics (ESHG) and the European Society of Human Reproduction and Embryology (ESHRE) have recently issued a recommendation for the introduction of targeted multigene panels, as expanded carrier screening [50,51]. Genetic tests based on parallel sequencing of several genes facilitate the process of gene investigation in infertility, reducing diagnostic costs and time [8], decreasing the current 20% rate of idiopathic infertility, and characterizing the different subtypes of male and female infertility [7,52].…”

Section: Genetic Diseasesmentioning

confidence: 99%

Unraveling the Balance between Genes, Microbes, Lifestyle and the Environment to Improve Healthy Reproduction

D’Argenio

Dittfeld²,

Lazzeri³

et al. 2021

Genes

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Humans’ health is the result of a complex and balanced interplay between genetic factors, environmental stimuli, lifestyle habits, and the microbiota composition. The knowledge about their single contributions, as well as the complex network linking each to the others, is pivotal to understand the mechanisms underlying the onset of many diseases and can provide key information for their prevention, diagnosis and therapy. This applies also to reproduction. Reproduction, involving almost 10% of our genetic code, is one of the most critical human’s functions and is a key element to assess the well-being of a population. The last decades revealed a progressive decline of reproductive outcomes worldwide. As a consequence, there is a growing interest in unveiling the role of the different factors involved in human reproduction and great efforts have been carried out to improve its outcomes. As for many other diseases, it is now clear that the interplay between the underlying genetics, our commensal microbiome, the lifestyle habits and the environment we live in can either exacerbate the outcome or mitigate the adverse effects. Here, we aim to analyze how each of these factors contribute to reproduction highlighting their individual contribution and providing supporting evidence of how to modify their impact and overall contribution to a healthy reproductive status.

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Sex chromosomes-linked single-gene disorders involved in human infertility

Cited by 12 publications

References 147 publications

A new TEX11 mutation causes azoospermia and testicular meiotic arrest

A new TEX11 mutation causes azoospermia and testicular meiotic arrest

Correlation scan: identifying genomic regions that affect genetic correlations applied to fertility traits

Unraveling the Balance between Genes, Microbes, Lifestyle and the Environment to Improve Healthy Reproduction

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