The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men

Kuroda-Kawaguchi, Tomoko; Skaletsky, Helen; Brown, Laura G.; Minx, Patrick; Cordum, Holland S.; Waterston, Robert H.; Wilson, Richard K.; Silber, Sherman J.; Oates, Robert D.; Rozen, Steve; Page, David C.

doi:10.1038/ng757

Cited by 603 publications

(669 citation statements)

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“…[29][30][31] For example, some studies reporting deletion between the distal arm of P1 to the proximal arm of P4 explained only those deletions that resulted from micro-deletions between direct repeat sequences that cause spermatogenic failure due to removal of Y chromosomal specific transcripts. 32 In our investigation, three of HERV-K14C related transcripts spanned on between P4 and P1.…”

Section: Herv-k14c Drove Y Chromosome Evolution H-s Sin Et Almentioning

confidence: 99%

Human endogenous retrovirus K14C drove genomic diversification of the Y chromosome during primate evolution

et al. 2010

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The male-specific region of Y chromosome (MSY) has accumulated a higher density of human endogenous retroviruses (HERVs) and related sequences when compared with other regions of the human genome. Here, we focused on one HERV family, HERV-K14C that seemed to integrate preferentially into the Y chromosome in humans. To identify every copies of HERV-K14C in the human genome, we applied computational screening to map precisely the locus of individual HERV-K14C copies. Interestingly, 29 of all 146 copies were located in Y chromosome, and these 29 copies were mostly dispersed in the palindromic region. Three distinct HERV-K14C-related transcripts were found and were exclusively expressed in human testis tissue. Based on our phylogenetic analysis of the solitary LTRs derived from HERV-K14C on the Y chromosome we suggested that these sequences were generated as pairs of identical sequences. Specifically, analysis of HERV-K14C-related sequences in the palindromic region demonstrated that the Y chromosomal amplicons existed in our common ancestors and the duplicated pairs arose after divergence of great apes approximately 8-10 million years ago. Taken together, our observation suggested that HERV-K14C-related sequences contributed to genomic diversification of Y chromosome during speciation of great ape lineage.

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Section: Herv-k14c Drove Y Chromosome Evolution H-s Sin Et Almentioning

confidence: 99%

Human endogenous retrovirus K14C drove genomic diversification of the Y chromosome during primate evolution

et al. 2010

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“…STS sY1192 (Genbank accession number: G67166) and STS sY1197 (G67168) were tested in duplex PCR and amplifications were carried out as already described [1]. STS sY1291 (G72340) amplification was performed (annealing temperature 65 • C) in duplex with the SRY gene STS (G38356) as control PCR amplification.…”

Section: Patientsmentioning

confidence: 99%

“…The human Y chromosome, which contains long, Y-specific repeats, is particularly susceptible to rearrangements such as deletions or duplication events generated by homologous recombination [1][2][3][4][5]. The interest of detecting Y chromosome rearrangements is becoming more and more important since the correlation between male infertility and Y chromosome microdeletions has been proved.…”

Section: Introductionmentioning

confidence: 99%

“…AZFc microdeletions have been shown to be caused by unequal recombination between two homologous sequences (b2 and b4 fragments) removing the 4 DAZ genes (Fig. 1) [1]. "Complete" AZFb deletions were found to extend from palindrome P5 to the proximal arm of palindrome P1, 1.5 Mb within AZFc, then eliminating the first cluster of DAZ genes (DAZ1 -DAZ2) ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative PCR technique for the identification of microrearrangements of the AZFc region

Rozé¹,

Bresson²,

Fellmann³

2007

J Assist Reprod Genet

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Purpose: The AZFc region spans about 3.5 Mb and contains many amplicons causing recombination events. Several papers have reported the occurrence of AZFc partial deletions resulting from non allelic homologous recombination (NAHR) ("gr-gr", "b1-b3" or "b2-b3" deletions), particularly in infertile patients. DAZ genes are present in 4 copies and rearrangements involve a modification of the number of DAZ genes.Methods: In addition to STS plus/minus PCR, we developed a quantitative technique using real time PCR (Q-PCR) to determine the number of DAZ genes. Fourteen DNA controls were selected to validate the use of Q-PCR to detect AZFc microrearrangements, and sperm DNA samples from 30 fertile men were studied.Results: Rearrangements of 14 controls were well identified with Q-PCR, and 2 AZFc partial deletions were detected in fertile men (1 "gr-gr" and 1 "b2-b3").Conclusion: Q-PCR represents a well-adapted method to detect microrearrangements of the Y-chromosome, complementary to STS analysis.V. Rozé ( ) EA MENRT 3185 Génétique et Reproduction -IFR133 IBCT,

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“…The human AZFc locus is palindromic and repetitive in nature, making it highly susceptible to intrachromosomal rearrangements during meiotic recombination. These intrachromosomal recombinations often lead to deletions/duplications and copy number variations of the eight gene families that are harboured within AZFc [9,10]. Amongst the various possible rearrangements that can occur, three major types of AZFc subdeletions viz.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

Sen

Ambulkar

Hinduja

et al. 2015

J Assist Reprod Genet

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Purpose The purpose of this study was to determine the association of AZFc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of DAZ and CDY1 gene copies with male infertility Methods Three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to AZFc subdeletion typing by STS PCR. Deletion of DAZ and CDY1 gene copies was done using sequence family variant analysis. Sperm concentration and motility were compared between men with and without AZFc subdeletions. Effect of the AZFc subdeletions on ICSI outcome was evaluated. Results Amongst the three AZFc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 %) and azoospermic (11.6 %) men as compared to controls (5.1 %). In men with AZFc subdeltions, loss of two DAZ and one CDY1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with OR of 29.7 and 26, respectively. These subdeletions had no effect on ICSI outcome, albeit there were an increased number of poor quality embryos in AZFc subdeleted group. Conclusion AZFc subdeletions are a major risk factor for male infertility in the Indian population. In the subjects with AZFc subdeletions, the deletion of DAZ and CDY1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. Since these deletions can be vertically transmitted to the future male offspring by ICSI, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation.

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The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men

Cited by 603 publications

References 46 publications

Human endogenous retrovirus K14C drove genomic diversification of the Y chromosome during primate evolution

Human endogenous retrovirus K14C drove genomic diversification of the Y chromosome during primate evolution

Quantitative PCR technique for the identification of microrearrangements of the AZFc region

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

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