Whole Exome Sequencing Identifies Genes Associated With Non-Obstructive Azoospermia

Zhang, Hongguo; Li, Wei; Jiang, Yuting; Li, Jia; Chen, Mucheng; Zhao, Jing; Peng, Zhiyu; Huang, Hui

doi:10.3389/fgene.2022.872179

Cited by 6 publications

(4 citation statements)

References 36 publications

(41 reference statements)

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“…Therefore, CYP19 may be a key candidate for modulating the concentration of spermatozoa in an ejaculate. Expression of ACTL8 has been reported to be isolated to the testes following a study that undertook exome sequencing in males with non-obstructive azoospermia [94], a condition where no sperm is present in an ejaculate due to failures during spermatogenesis [95]. In the same study, mutations in ACTL8 were not present in the control patients.…”

Section: Discussionmentioning

confidence: 98%

QTLs and Candidate Genes Associated with Semen Traits in Merino Sheep

Hodge

Heras‐Saldana

Rindfleish³

et al. 2023

Animals

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Ram semen traits play a significant role in conception outcomes, which in turn may influence reproductive efficiency and the overall productivity and profitability of sheep enterprises. Since hundreds of ewes may be inseminated from a single ejaculate, it is important to evaluate semen quality prior to use in sheep breeding programs. Given that semen traits have been found to be heritable, genetic variation likely contributes to the variability observed in these traits. Identifying such genetic variants could provide novel insights into the molecular mechanisms underlying variability in semen traits. Therefore, this study aimed to identify quantitative trait loci (QTLs) associated with semen traits in Merino sheep. A genome-wide association study (GWAS) was undertaken using 4506 semen collection records from 246 Merino rams collected between January 2002 and May 2021. The R package RepeatABEL was used to perform a GWAS for semen volume, gross motility, concentration, and percent post-thaw motility. A total of 35 QTLs, located on 16 Ovis aries autosomes (OARs), were significantly associated with either of the four semen traits in this study. A total of 89, 95, 33, and 73 candidate genes were identified, via modified Bonferroni, within the QTLs significantly associated with volume, gross motility, concentration, and percent post-thaw motility, respectively. Among the candidate genes identified, SORD, SH2B1, and NT5E have been previously described to significantly influence spermatogenesis, spermatozoal motility, and high percent post-thaw motility, respectively. Several candidate genes identified could potentially influence ram semen traits based on existing evidence in the literature. As such, validation of these putative candidates may offer the potential to develop future strategies to improve sheep reproductive efficiency. Furthermore, Merino ram semen traits are lowly heritable (0.071–0.139), and thus may be improved by selective breeding.

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Section: Discussionmentioning

confidence: 98%

QTLs and Candidate Genes Associated with Semen Traits in Merino Sheep

Hodge

Heras‐Saldana

Rindfleish³

et al. 2023

Animals

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“…The sequencing parameters were single-end sequencing, with a read length of 35 bp and a minimum of 18 million reads [ 12 ]. Whole-exome sequencing was performed using the SureSelect Human All Exon V6 capture chip, with paired-end sequencing and a read length of 100 bp [ 13 ]. The average sequencing depth was 180X.…”

Section: Methodsmentioning

confidence: 99%

Identification of a novel intronic mutation of MAGED2 gene in a Chinese family with antenatal Bartter syndrome

Yan,

Hu,

Zhang

et al. 2024

BMC Med Genomics

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Background Antenatal Bartter syndrome is a life-threatening disease caused by a mutation in the MAGED2 gene located on chromosome Xp11. It is characterized by severe polyhydramnios and extreme prematurity. While most reported mutations are located in the exon region, variations in the intron region are rarely reported. Methods In our study, we employed whole exome sequencing and Sanger sequencing to genotype members of this family. Additionally, a minigene assay was conducted to evaluate the impact of genetic variants on splicing. Results Our findings reveal a novel intronic variant (NM_177433.3:c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene. Further analysis using the minigene assay demonstrated that this variant activated an intronic cryptic splice site, resulting in a 96 bp insertion in mature mRNA. Conclusions Our results indicate that the novel intronic variant (c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene is pathogenic. This expands the mutation spectrum of MAGED2 and highlights the significance of intronic sequence analysis.

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“…The genetic factors related to these pathological conditions include chromosome abnormalities, azoospermia factor microdeletion, genetic variations, epigenetic changes, etc. [4][5][6] Reciprocal chromosomal translocation (RCT) is an important chromosome structural abnormality and has been reported to affect sperm number, morphology, and motility. [7,8] AZS is the commonest causes of male-related infertility [9] and often diagnosed due to reduced sperm motility.…”

Section: Introductionmentioning

confidence: 99%

Association between chromosome 6p21 translocation and asthenozoospermia: A retrospective, observational study

et al. 2023

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Asthenozoospermia (AZS) is the commonest cause of male-related infertility. The patients with AZS easily exhibit infertility, with their wives having spontaneous miscarriages or seeking assisted reproductive treatment. Reciprocal chromosomal translocation (RCT) is an important chromosome structural abnormality and has been reported to affect sperm motility. Genetic counseling for male RCT patients with AZS is still a challenge. This study reported 4 RCT carriers, which were 46,XY,t(1;6) (p36.1;p21), 46,XY,t (6;10) (p21;q11.2), 46,XY,t (6;11) (p21;p15), and 46,XY,t (6;17) (p21;q21), respectively. The association between chromosome 6p21 translocation and AZS is discussed, considering 19 published cases as well. In 6 patients with available semen parameters and 4 patients in this study, all of them were diagnosed with AZS. The SLC26A8 gene and the DNAH8 gene located on chromosome 6p21 are closely related to AZS by gene search using OMIM. For the chromosome 6p21 breakpoint, 72 pathogenic genes were found through the DECIPHER search. Gene ontology analysis showed that these target genes have several molecular functions and are strongly involved in various biological processes. The proteins expressed by these genes are involved in multiple cellular components. These results suggest that the breakpoint of chromosome 6p21 in male RCT carriers is closely related to AZS. The breakpoint may disrupt the structure and function of related genes, resulting in reduced sperm motility. Karyotype analysis should be recommended for AZS patients. Chromosomes and breakpoints involved in RCT should be paid attention to in genetic counseling for patients.

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Whole Exome Sequencing Identifies Genes Associated With Non-Obstructive Azoospermia

Cited by 6 publications

References 36 publications

QTLs and Candidate Genes Associated with Semen Traits in Merino Sheep

QTLs and Candidate Genes Associated with Semen Traits in Merino Sheep

Identification of a novel intronic mutation of MAGED2 gene in a Chinese family with antenatal Bartter syndrome

Association between chromosome 6p21 translocation and asthenozoospermia: A retrospective, observational study

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