Identification of new breakpoints in AZFb and AZFc

Costa, Paula Cristina Pereira da; Gonçalves, Rita; Ferrás, Cristina; Fernandes, Susana; Fernandes, Ana; Sousa, Mário; Barros, Alberto

doi:10.1093/molehr/gan014

Cited by 37 publications

(41 citation statements)

References 40 publications

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“…Interestingly, the T allele was observed in our two patients with AZFb and in one-third of patients with AZFb+c deletions, suggesting that subjects with the T allele on DYS199 locus would have a Y chromosome with a particular sequence variation, or a particular structure that predispose to suffer AZFb microdeletions. Since our two patients with AZFb deletions and the Q1a3a haplogroup have the previously reported P5/proximal-P1 and P4/proximal-P1 deletion, the mechanism involved would increase the susceptibility to homologous recombination between arms of palindromes P5 or P4 and the arm P1.2 of the P1 palindrome [11,27,34]. Therefore, some sequence variations associated with the T allele on DYS199 locus, likely localized within or between the P5/P4 and P1 palindromes might lead to a higher AZFb deletion susceptibility.…”

Section: Resultsmentioning

confidence: 60%

Greater prevalence of Y chromosome Q1a3a haplogroup in Y-microdeleted Chilean men: a case–control study

Lardone

Marengo

Parada-Bustamante

et al. 2013

J Assist Reprod Genet

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Purpose To determine the prevalence of South Amerindian Y chromosome in Chilean patients with spermatogenic failure and their association with classical and/or AZFc-partial Y chromosome deletions. Methods We studied 400 men, 218 with secretory azo/oligozoospermia (cases) and 182 controls (116 fertile and/or normozoospermic, and 66 azoospermic with normal spermatogenesis). After a complete testicular characterization (physical evaluation, hormonal and/or biopsy) peripheral blood was drawn to obtain DNA for Y chromosome microdeletions, AZFc-partial deletions and biallelic analysis by allele specific polymerase chain reaction (PCR) of the M3 (rs3894) single nucleotide polymorphism (SNP). Results Classical AZF microdeletions were found in 23 cases (Y-microdeleted). AZFc-partial deletions were observed in 10 cases (6 "gr/gr", 3 "b2/b3" and 1 "b1/b3") and 4 controls (4 "gr/gr"). The AZFc-partial deletions were mainly associated with the absence of DAZ1/DAZ2 (64 %). No significant differences in the prevalence of AZFc-partial deletions were observed between cases and controls. We observed a significant higher proportion of the Q1a3a haplogroup in Y-microdeleted men compared to patients with spermatogenic failure without deletions and control men (P<0.01 and P<0.05, respectively by Bonferroni test). Among them, patients with AZFb deletions had an increased prevalence of the Q1a3a haplogroup compared to controls, cases without deletions and to those with complete or partial-AZFc deletions (P<0.01, Bonferroni test). Conclusions The Q1a3a South Amerindian lineage seems to increase the susceptibility to non AZFc microdeletions. On the other hand, in Chilean population the AZFc-partial deletions ("gr/gr", "b1/b3" and/or "b2/b3") does not seem to predispose to severe spermatogenic impairment.

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Section: Resultsmentioning

confidence: 60%

Greater prevalence of Y chromosome Q1a3a haplogroup in Y-microdeleted Chilean men: a case–control study

Lardone

Marengo

Parada-Bustamante

et al. 2013

J Assist Reprod Genet

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“…In the so-called 'AZFb + AZFc' deletions, homologous recombination between P5 and the distal P1 arm removes 7.7 Mb of DNA, about one quarter of the Y chromosome euchromatic region, and 42 genes. There are other atypical AZFb deletions that lack direct repeats at their breakpoints [Repping et al, 2002;Yang et al, 2007;Costa et al, 2008]. They are likely the products of nonhomologous end-joining.…”

Section: The Azfb Deletionmentioning

confidence: 99%

Genetics of Spermatogenic Failure

Huang

Yen

2008

Sex Dev

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Spermatogenesis is an ongoing developmental process in adult testes that requires the coordinated expression of many genes. The genetic causes of spermatogenic failure in men remain largely unknown, though abnormalities in the sex chromosomes constitute a significant portion of them. In this review, we focus on 3 disorders that involve the sex chromosomes and are often screened in infertility clinics. These are Klinefelter syndrome, Y chromosome microdeletion, and XX male syndrome. We describe their prevalence, the associated phenotypes, and the molecular mechanisms underlying the disorders and discuss the difficulties in identifying the causal genes contributing to the spermatogenic defects. Currently, there are no effective therapies for the spermatogenic failure in the patients, and conception through assisted reproductive technology bears the risk of passing genetic abnormalities to the next generation.

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“…More partial AZFb deletions associated with variable testicular histologies but not meiotic arrest and with distal breakpoints concentrated in the overlapping genomic AZFb-AZFc interval have been described in the literature [80][81][82] . Unfortunately, most of them did not address the basic question of whether the observed partial AZFb microdeletion was "de novo," and thus only found on the patients' Y chromosomes, or polymorphic because it was also found on the Y chromosomes of their fertile fathers.…”

Section: Azfb Gene Deletions and Male Infertilitymentioning

confidence: 99%

Human Y Chromosome and Male Infertility: Forward and Back from Azoospermia Factor Chromatin Structure to Azoospermia Factor Gene Function

Vogt¹,

Bender²,

Zimmer³

et al. 2017

Genetics of Human Infertility

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In the euchromatic part of the long arm of the human Y chromosome (Yq11) at least 13 Y genes encoding proteins and expressed in male germ cells were found in 3 distinct genomic Y regions frequently deleted in infertile men with idiopathic azoospermia, i.e., for unknown reasons no mature sperm were found in their semen fluid. Accordingly, they were designated as azoospermia factor (AZF) regions: AZFa, AZFb, and AZFc. Additionally, 10 Y genes called "testis-specific transcript Y" ( TTTY ) genes were mapped in the same AZF intervals. They belong to the long non-coding RNA gene pool in human germ cells because they seem to lack any protein-coding potential. Distinct chromatin regions in Yq11 overlapping with AZFb and AZFc are supposed to be involved in the premeiotic X and Y chromosome pairing and inactivation process controlling male germ cell meiosis. It can thus be assumed that the germ line function of the AZF loci in Yq11 may be not only based on the expression of some germ cell proteins, but also on the expression of some germ cell-specific TTTY transcripts and a locally dynamic and specific chromatin folding structure probably controlled by some germ cell-specific nuclear proteins.

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Identification of new breakpoints in AZFb and AZFc

Cited by 37 publications

References 40 publications

Greater prevalence of Y chromosome Q1a3a haplogroup in Y-microdeleted Chilean men: a case–control study

Greater prevalence of Y chromosome Q1a3a haplogroup in Y-microdeleted Chilean men: a case–control study

Genetics of Spermatogenic Failure

Human Y Chromosome and Male Infertility: Forward and Back from Azoospermia Factor Chromatin Structure to Azoospermia Factor Gene Function

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