gr/gr- DAZ2-DAZ4-CDY1b deletion is a high-risk factor for male infertility in Tunisian population

Ghorbel, Myriam; Baklouti-Gargouri, Siwar; Keskes, Rim; Chakroun, N.; Sellami, Afifa; Fakhfakh, Faïza; Ammar-Keskes, Leila

doi:10.1016/j.gene.2016.07.050

Cited by 8 publications

(4 citation statements)

References 40 publications

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“…Based on analyses of gene copy deletions in the AZFc locus of infertile men, Machev et al [ 148 ] discriminated four types of DAZ - CDY1 partial deletions and found that only one deletion type, DAZ3/4-CDY1a , was associated with male infertility. In a similar study concomitant deletion of both DAZ and CDY1 copies in males predisposes them to azoospermia or severe oligozoospermia [ 140 , 149 ] deletion of CDY1b copy alone is also reported to be associated with oligo/azoospermia [ 150 ]. However, the fact that some men with CDY1 deletions (alone or in combination with DAZ ) are fertile/normozoopermic suggest that these genes are not indispensible for spermatogenesis [ 140 , 151 ].…”

Section: Chromodomain Protein Y Linked [ Cdy ]mentioning

confidence: 99%

“…It is shown that not all men with gr/gr deletions have identical amounts of DNA lost. Based on copy number estimates of DAZ and CDY1 genes, it is observed that only those men with two DAZ and one CDY1 copy deleted will have azoospermia or oligozoospermia, retention of any one of these genes will be almost always be associated with normozoospermia [ 139 , 140 , 143 , 145 , 149 ]. Along with DAZ and CDY1 , studies have also identified GOLGA2LY and BPY2 copy numbers have a protective effect on fertility of men with gr/gr deletions [ 138 , 143 , 157 ].…”

Section: Prevalence Of Partial Azfc Deletions and Male Infertilitymentioning

confidence: 99%

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Genetics of the human Y chromosome and its association with male infertility

Colaco

Modi

2018

Reprod Biol Endocrinol

208

177

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The human Y chromosome harbors genes that are responsible for testis development and also for initiation and maintenance of spermatogenesis in adulthood. The long arm of the Y chromosome (Yq) contains many ampliconic and palindromic sequences making it predisposed to self-recombination during spermatogenesis and hence susceptible to intra-chromosomal deletions. Such deletions lead to copy number variation in genes of the Y chromosome resulting in male infertility. Three common Yq deletions that recur in infertile males are termed as AZF (Azoospermia Factor) microdeletions viz. AZFa, AZFb and AZFc. As estimated from data of nearly 40,000 Y chromosomes, the global prevalence of Yq microdeletions is 7.5% in infertile males; however the European infertile men are less susceptible to Yq microdeletions, the highest prevalence is in Americans and East Asian infertile men. In addition, partial deletions of the AZFc locus have been associated with infertility but the effect seems to be ethnicity dependent. Analysis of > 17,000 Y chromosomes from fertile and infertile men has revealed an association of gr/gr deletion with male infertility in Caucasians and Mongolian men, while the b2/b3 deletion is associated with male infertility in African and Dravidian men. Clinically, the screening for Yq microdeletions would aid the clinician in determining the cause of male infertility and decide a rational management strategy for the patient. As these deletions are transmitted to 100% of male offspring born through assisted reproduction, testing of Yq deletions will allow the couples to make an informed choice regarding the perpetuation of male infertility in future generations. With the emerging data on association of Yq deletions with testicular cancers and neuropsychiatric conditions long term follow-up data is urgently needed for infertile men harboring Yq deletions. If found so, the information will change the current the perspective of androgenetics from infertility and might have broad implication in men health.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0330-5) contains supplementary material, which is available to authorized users.

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Section: Chromodomain Protein Y Linked [ Cdy ]mentioning

confidence: 99%

Section: Prevalence Of Partial Azfc Deletions and Male Infertilitymentioning

confidence: 99%

Genetics of the human Y chromosome and its association with male infertility

Colaco

Modi

2018

Reprod Biol Endocrinol

208

177

View full text Add to dashboard Cite

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“…To our knowledge, no other Y-lineage specific risk variants for spermatogenic impairment have been reported so far. Previously, the DAZ2-DAZ4 deletion had been shown as a high-risk factor for male infertility in the Tunisian population, but the Y haplogroups of those subjects was not investigated ( 24 ). The survival of such a high-risk lineage in the population seems at first sight surprising, but may be accounted for by its possible age-specific effects on spermatogenesis, which may be exacerbated by the recent general decline in sperm count ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Y chromosomes carrying partial AZFc deletions may differ for the content, dosage or genetic variability of the retained genes, the overall genetic composition reflected by phylogenetic haplogroups or the presence of additional structural variants. Only limited studies have analyzed the subtypes of gr/gr or b2/b3 deletions and no straightforward conclusions have been reached for their link to spermatogenic failure ( 17, 24, 25 ).…”

Section: Introductionmentioning

confidence: 99%

A common 1.6 Mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans

Kibena

Punab

Arciero

et al. 2020

Preprint

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Male infertility is a prevalent condition, concerning 5-10% of men. So far, only some recurrent genetic factors have been described as confident contributors to spermatogenic failure. Here, we report the first re-sequencing study of the Y-chromosomal Azoospermia Factor c (AZFc) region combined with gene dosage and Y-haplogroup determination. In analysing 2,324 Estonian men, we uncovered a novel structural variant as a high-penetrant risk factor to male infertility. The Y lineage R1a1-M458, reported at >20% frequency in several European populations, carries a fixed ∼1.6 Mb long r2/r3 inversion destabilizing the AZFc region and predisposing to recurrent microdeletions. Such complex rearrangements were significantly enriched among severe oligozoospermia cases. The carrier vs non-carrier risk to spermatogenic failure was increased 8.6-fold (p = 6.0 × 10−4). The finding contributes to improved molecular diagnostics and clinical management of infertility. Carrier identification in young age will facilitate timely counselling and reproductive decision-making.

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