Development of a high-resolution Y-chromosome microarray for improved male infertility diagnosis

Yuen, Ryan K. C.; Merkoulovitch, Anna; MacDonald, Jeffrey R.; Vlasschaert, Matthew; Lo, Kirk; Grober, Ethan; Marshall, Christian R.; Jarvi, Keith; Kolomietz, Elena; Scherer, Stephen W.

doi:10.1016/j.fertnstert.2013.12.027

Cited by 30 publications

(31 citation statements)

References 23 publications

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“…This is because it is difficult to design probes for the Y chromosome owing to the highly repetitive nature of its sequence, and many commercially available arrays do not assay it 57 . For losses, the highest proportion of variable sequence was in chromosomes 19 and 22 and the Y chromosome on both inclusive and stringent maps (FIG.…”

Section: Copy Number Stablementioning

confidence: 99%

A copy number variation map of the human genome

et al. 2015

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A major contribution to the genome variability among individuals comes from deletions and duplications - collectively termed copy number variations (CNVs) - which alter the diploid status of DNA. These alterations may have no phenotypic effect, account for adaptive traits or can underlie disease. We have compiled published high-quality data on healthy individuals of various ethnicities to construct an updated CNV map of the human genome. Depending on the level of stringency of the map, we estimated that 4.8-9.5% of the genome contributes to CNV and found approximately 100 genes that can be completely deleted without producing apparent phenotypic consequences. This map will aid the interpretation of new CNV findings for both clinical and research applications.

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Section: Copy Number Stablementioning

confidence: 99%

A copy number variation map of the human genome

et al. 2015

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“…3 Although assisted reproductive techniques (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), allow men with suboptimal sperm quality to overcome natural selection mechanisms and produce a viable zygote, the advent of ART has emphasized the necessity and importance of elucidating the genetic basis of male infertility because inheritance of mutations passed on through ART can cause unacceptable serious consequences. 4, 5, 6 Given that many non-obstructive causes of male infertility are unexplained and the therapeutic effect is beyond the power of hormone and ART, focussing on genetic causes and identifying genes and pathways associated with infertility becomes a public health priority. 7 On the other hand, few approaches other than barrier methods have been adequately developed for male contraception.…”

Section: Open Questionsmentioning

confidence: 99%

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

et al. 2016

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Male infertility due to abnormal spermatozoa has been reported in both animals and humans, but its pathogenic causes, including genetic abnormalities, remain largely unknown. On the other hand, contraceptive options for men are limited, and a specific, reversible and safe method of male contraception has been a long-standing quest in medicine. Some progress has recently been made in exploring the effects of spermatid-specifical genetic factors in controlling male fertility. A comprehensive search of PubMed for articles and reviews published in English before July 2016 was carried out using the search terms ‘spermiogenesis failure', ‘globozoospermia', ‘spermatid-specific', ‘acrosome', ‘infertile', ‘manchette', ‘sperm connecting piece', ‘sperm annulus', ‘sperm ADAMs', ‘flagellar abnormalities', ‘sperm motility loss', ‘sperm ion exchanger' and ‘contraceptive targets'. Importantly, we have opted to focus on articles regarding spermatid-specific factors. Genetic studies to define the structure and physiology of sperm have shown that spermatozoa appear to be one of the most promising contraceptive targets. Here we summarize how these spermatid-specific factors regulate spermiogenesis and categorize them according to their localization and function from spermatid head to tail (e.g., acrosome, manchette, head-tail conjunction, annulus, principal piece of tail). In addition, we emphatically introduce small-molecule contraceptives, such as BRDT and PPP3CC/PPP3R2, which are currently being developed to target spermatogenic-specific proteins. We suggest that blocking the differentiation of haploid germ cells, which rarely affects early spermatogenic cell types and the testicular microenvironment, is a better choice than spermatogenic-specific proteins. The studies described here provide valuable information regarding the genetic and molecular defects causing male mouse infertility to improve our understanding of the importance of spermatid-specific factors in controlling fertility. Although a male contraceptive ‘pill' is still many years away, research into the production of new small-molecule contraceptives targeting spermatid-specific proteins is the right avenue.

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“…Genetic abnormalities have been generally considered to be a main risk factor of idiopathic NOA (Hamada et al ., ; Rayburn, ). Currently, the techniques of chromosomal analysis and Y chromosome microdeletion detection screening are valuable for clinical diagnosis and therapy of male infertility with azoospermia (Hammami et al ., ; Yuen et al ., ). But so far, the pathogenicity factors of more than 50% of azoospermia are still unknown (Zhang et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Association and meta-analysis of HLA and non-obstructive azoospermia in the Han Chinese population

et al. 2016

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The exact aetiology and pathogenesis of most non-obstructive azoospermia (NOA) are still unknown. The previous two genomewide association studies (GWASs) have identified three different loci within the HLA region for NOA in the Han Chinese population, including rs3129878, rs498422 and rs7194. To further validate the risk of three GWAS-linked loci for NOA, we conducted a case-control study of these three risk loci in an independent Han Chinese male population, with 603 NOA patients and 610 controls. Furthermore, we also performed a meta-analysis of five studies on these three NOA-risk loci. The case-control study strongly suggested a significant association between loci rs3129878, rs498422 and rs7194 and NOA (P = 6.75 × 10 (OR = 2.2586), P = 0.0060 (OR = 1.4013) and P = 0.0128 (OR = 1.2626) respectively). Our meta-analyses also supported the susceptibility of these three risk loci to NOA (P < 0.01). The risk variants within the HLA region potentially have a strong effect on males at risk of NOA, and may serve as diagnostic markers for male infertility. However, considering genetic difference between different populations, future validating studies in larger independent samples and animal experiments are suggested.

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Development of a high-resolution Y-chromosome microarray for improved male infertility diagnosis

Cited by 30 publications

References 23 publications

A copy number variation map of the human genome

A copy number variation map of the human genome

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

Association and meta-analysis of HLA and non-obstructive azoospermia in the Han Chinese population

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