Partial duplication at<i>AZFc</i>on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan

Lin, Yen-Hui; Hsu, Lea Chia-Ling; Kuo, Pao‐Lin; Huang, William W.; Chiang, Han-Sun; Yeh, Shauh-Der; Hsu, Tuan-Yi; Yu, Yueh‐Hsiang; Hsiao, Kuang-Nan; Cantor, Rita M.; Yen, Pauline H.

doi:10.1002/humu.20473

Cited by 96 publications

(111 citation statements)

References 44 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In conclusion, discrepant results were detected regarding gene copy loss when multiple SFVs were compared in 27% (4/15) of DAZ3/DAZ4 deletions and 13% (1/8) in DAZ1/DAZ2 deletions. These Wgures are concordant with other studies in which these eVects have previously been reported as a consequence of gene conversion Lin et al 2007;Navarro-Costa et al 2007;StouVs et al 2008). …”

Section: Daz and Cdy1 Gene Copy Dewnitionsupporting

confidence: 93%

“…Ours is the Wrst study in a Caucasian population and the discordance with the only study reporting such an association, based on a Han-Chinese population (Lin et al 2007), may reXect genuine ethnic diVerences or related to diVerent sample sizes. Table 5 Comparison of gr/gr deletion frequencies between the following three diVerent study populations: Giachini et al (2005); replication of the previous study on an independent sample set; combination of the two study populations a Twenty-nine subjects with a history of monolateral cryptorchidism originating from the Giachini et al 2005 …”

Section: Discussionmentioning

confidence: 71%

“…Since the inclusion criteria for controls were diVerent in diVerent studies (general population or proven fertile men with unknown sperm count or normozoospermic men), the percentage of normozoospermic men in each control group is indicated a Gene dosage was performed only in these studies (i.e., only in four of the 16 studies) which spans 1.8 Mb and involves 12 genes. The authors found an association between AZFc partial duplications and male infertility (Lin et al 2007). The authors suggested that some AZFc gene would be dosage-sensitive and their increased expression may interfere with normal spermatogenesis.…”

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Partial AZFc deletions and duplications: clinical correlates in the Italian population

et al. 2008

View full text Add to dashboard Cite

The role of partial AZFc deletions of the Y chromosome in spermatogenic impairment is currently debated. Recently, it was also reported that duplications of the same region are associated with oligozoospermia in Han-Chinese men. The aims of this study were (1) to evaluate the clinical signiWcance of partial AZFc deletions in a large study population and (2) to deWne if partial AZFc duplications are a risk factor for spermatogenic failure also in a Caucasian population such as the Italian. We screened 556 infertile patients and 487 normozoospermic controls for partial AZFc deletions with a combined method based on STS+/¡ followed by CDY1-DAZ gene dosage and copy analysis. For the second aim, we performed CDY1-DAZ gene dosage in 229 infertile patients and 263 normozoospermic controls. The frequency of gr/gr deletions in patients was signiWcantly diVerent from the controls (3.2 vs. 0.4%, respectively; P < 0.001), with an OR = 7.9 (95% CI 1.8-33.8). b2/b3 deletions were rare in both groups (0.5% in patients, 0.2% in controls). Concerning gr/gr duplications, we observed no signiWcant diVerences in their frequency between cases (2.6%) and controls (3.8%). This is the largest study population in the literature in which all potential methodological and selection biases were carefully avoided to detect the clinical signiWcance of partial AZFc deletions and duplications. Our study provides strong evidence that gr/gr deletion is a risk factor for impaired spermatogenesis, whereas we did not detect a signiWcant eVect of b2/b3 deletions and partial AZFc duplications on spermatogenesis in this Caucasian ethnic group.

show abstract

Section: Daz and Cdy1 Gene Copy Dewnitionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Partial AZFc deletions and duplications: clinical correlates in the Italian population

et al. 2008

View full text Add to dashboard Cite

show abstract

“…9,10 In addition to the classical AZFc deletion, several recurrent partial deletions (named gr/gr, b2/b3 and b1/b3) and duplications (b2/b4 duplication) have been reported. 11,12 Even though all partial rearrangements produce either a decrease or an increase in AZFc gene dosage, only the 'gr/gr deletion' resulted to be clinically relevant. The clinical significance of this recurrent deletion has been object of a long-lasting debate.…”

Section: Introductionmentioning

confidence: 99%

“…To date, only two groups have addressed this topic in the Taiwanese and Italian populations, reaching contradictory conclusions. 12,20 In addition, by using a consecutive cohort study model, Noordam et al 21 suggested that both lower and higher DAZ gene dosage could be deleterious for spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory

et al. 2013

View full text Add to dashboard Cite

AZF microdeletion screening is routinely performed in the diagnostic work-up for male infertility; however, some issues remain debated. In this study, we provide insights into the sperm concentration cutoff value for routine testing, the predictive value of AZFc deletion for testicular sperm retrieval and the Y-background contribution to the interpopulation variability of deletion frequencies. In the Spanish population, partial AZFc rearrangements have been poorly explored and no data exist on partial duplications. In our study, 27/806 (3.3%) patients carried complete AZF deletions. All were azoo/cryptozoospermic, except for one whose sperm concentration was 2 Â 10 6 /ml. In AZFc-deleted men, we observed a lower sperm recovery rate upon conventional TESE (9.1%) compared with the literature (60-80% with microTESE). Haplogroup E was the most represented among non-Spanish and hgr P among Spanish AZF deletion carriers. The analysis of AZFc partial rearrangements included 330 idiopathic infertile patients and 385 controls of Spanish origin. Gr/gr deletion, but not AZFc partial duplications, was significantly associated with spermatogenic impairment. Our data integrated with the literature suggest that: (1) routine AZF microdeletion testing could eventually include only men with r2 Â 10 6 /ml; (2) classical TESE is associated with low sperm recovery rate in azoospermic AZFc-deleted men, and therefore microTESE should be preferred; (3) Y background could partially explain the differences in deletion frequencies among populations. Finally, our data on gr/gr deletion further support the inclusion of this genetic test in the work-up of infertile men, whereas partial AZFc duplications do not represent a risk for spermatogenic failure in the Spanish population.

show abstract

Molecular Genetics of Spermatogenic Disturbances

Krausz¹

2009

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

A large proportion of male infertility is predicted to be related to genetic factors. These factors may act directly at the testicular level or through the endocrine regulation of the testis. A number of new causative mutations have been identified in hypogonadotrophic hypogonadism allowing a genetic diagnosis in approximately 30–40% of cases. However, search for causative mutations in Y‐chromosome, autosomal and X‐linked genes with predicted spermatogenic function have been substantially unsuccessful with some rare exceptions. Up to now, only Y‐chromosome rearrangements such as AZoospermia Factor ( AZF ) deletions and gr/gr deletion have been confirmed as molecular genetic causes of primitive testicular failure. Key concepts: Spermatogenic failure can be caused by genetic factors acting at the pre‐testicular or directly at the testicular level. Mutation in genes involved in the hormonal regulation of the testis (pre‐testicular level) is associated with hypogonadotrophic hypogonadism. Genetic factors involved in primitive testicular failure can be divided in chromosomal abnormalities and monogenic mutations. Microdeletions in specific regions of the long arm of the Y‐chromosome ( AZF regions) represent the most frequent molecular genetic cause of primitive testicular failure. The diagnosis of AZF deletions is clinically relevant since it provides the aethiology of infertility, has a prognostic value for testicular sperm retrieval and the deletion will be obligatory transmitted to the male offspring. gr/gr deletion of the AZFc region is the only significant risk factor for impaired sperm production identified to date. Search for X‐linked and autosomal gene mutations/polymorphisms has been largely unsuccessful. Given the polygenic nature of male infertility a major advancement will likely be achieved from future studies based on whole genome analyses in large study populations.

show abstract

Partial duplication atAZFcon the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan

Cited by 96 publications

References 44 publications

Partial AZFc deletions and duplications: clinical correlates in the Italian population

Partial AZFc deletions and duplications: clinical correlates in the Italian population

Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory

Molecular Genetics of Spermatogenic Disturbances

Contact Info

Product

Resources

About