Genomic heterogeneity and instability of the AZF locus on the human Y chromosome.
TL;DR: A genetic redundancy of the multi-copy genes in AZFb and AZFc and a causative relationship between the occurrence of first microdeletions then macro deletions in the repetitive structure of Yq11 is suggested where large palindromes are probably promoting multiple gene conversions andAZF rearrangements.
About: This article is published in Molecular and Cellular Endocrinology.The article was published on 2004-09-30. It has received 88 citations till now. The article focuses on the topics: Azoospermia factor.
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TL;DR: A clinical karyotype report involving a Y chromosome abnormality should consider the results of semen analysis, which helps to identify the chromosomal breakpoint, which was useful for clarifying AZF gene microdeletions.
2 citations
Cites background from "Genomic heterogeneity and instabili..."
...The clinical phenotypes of Y:autosome translocations are also related the Y chromosome microdeletions.([16]) In general, carriers of AZF-deletions on the long arm of the Y chromosome appear to be azoospermic....
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2 citations
01 May 2013
TL;DR: The detection of frequency and incidence of AZF microdeletions in North-East Indian states with special reference to AZFa and AZFd region of long arm of Y chromosome shows that markers not specified by EAA are also good enough in determining Y chromosome micro deletion in the present population.
Abstract: Introduction: The first cases of Y chromosome microdeletions and male infertility were reported in 1992 and many case series have subsequently been reported from various parts of the world. A very few studies have been done involving the patients of North-East Indian states, so this study aimed to detect frequency and incidence of AZF microdeletions in this population with special reference to AZFa and AZFd region of long arm of Y chromosome. Aims: The main objectives involve - a) Determination of microdeletion frequency for each type of infertility group included in the study. b) Determination and comparison of the microdeletion frequency of Y chromosomal AZFa and AZFd region in the cases using 2 gene-specific markers: USP9Y, DBY and 3 STS markers: sY145, sY152, sY153. c) Evaluation of the importance of using markers, not specified by European Academy of Andrology (EAA) to detect Y chromosome microdeletion, in Indian scenario. Methods: A total of 170 infertile males attending private infertility clinics of Guwahati, Assam were selected for the study. This includes 50 azoospermic, 82 oligozoospermic, 18 oligoasthenozoospermic and 20 asthenozoospermic cases. Both blood and semen samples were collected from 45 individuals. PCR amplification was carried out using specific primer sets and isolated genomic DNA. All genes and STS markers were amplified efficiently in samples from 50 fertile men tested, but failed to be amplified in samples from fertile women. Results: The frequency of Y chromosome microdeletion with respect to AZFa and AZFd region was found to be 25.3% (43/170). In azoospermic, oligozoospermic, oligoasthenozoospermic and asthenozoospermic cases it was found to be 28% (14/50), 26.8% (22/82), 11.1% (2/18) and 25% (5/20) respectively. In the cases with single marker microdeletion, microdeletion of only DBY gene was found to be associated with all the four infertility groups. In the 45 individuals from whom both blood and semen samples were available, frequency of Y chromosome microdeletion was found to be higher in semen samples (20%) than blood (17.8%) samples. Conclusion: It shows that markers not specified by EAA are also good enough in determining Y chromosome microdeletion in the present population. We also suggest that the use of DNA isolated from semen sample, for Y chromosome microdeletion screening can be a better option as it can detect the deletions not detected by blood sample analysis.
2 citations
TL;DR: La valoracion y los estudios geneticos de pacientes con infertilidad masculina son importantes para conocer the causa y otorgar un adecuado asesoramiento genetico.
2 citations
Additional excerpts
...Oligoastenoteratozoospermia 32,43 (23-40) 19 19 0 9 2 11...
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...Criptozoospermia 31,32 (24-35) 4 3 1 2 1 3...
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...Oligozoospermia 31,41 (23-41) 14 14 0 14 0 14...
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...Oligoastenozoospermia 32,52 (26-42) 9 9 0 8 0 8...
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...Oligoteratozoospermia 31,68 (24-36) 7 7 0 2 0 2...
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References
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TL;DR: The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length, and is a mosaic of heterochromatic sequences and three classes of euchromatics sequences: X-transposed, X-degenerate and ampliconic.
Abstract: The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length. Here, we report that the MSY is a mosaic of heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X-degenerate and ampliconic. These classes contain all 156 known transcription units, which include 78 protein-coding genes that collectively encode 27 distinct proteins. The X-transposed sequences exhibit 99% identity to the X chromosome. The X-degenerate sequences are remnants of ancient autosomes from which the modern X and Y chromosomes evolved. The ampliconic class includes large regions (about 30% of the MSY euchromatin) where sequence pairs show greater than 99.9% identity, which is maintained by frequent gene conversion (non-reciprocal transfer). The most prominent features here are eight massive palindromes, at least six of which contain testis genes.
2,022 citations
TL;DR: The presence of not one but three spermatogenesis loci in Yq11 is proposed and that each locus is active during a different phase of male germ cell development.
Abstract: In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia wereanalysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involvingseveral DNA loci, while an additional patient had an inherited deletion. They were mapped to three differentsubregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second andthird subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletionsobserved were not overlapping but the extension of the deleted Y DNA in each subregion was similar in eachpatient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phasewhen the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletionoccurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesisloci in Yq11 and that each locus is active during a different phase of male germ cell development. As the mostsevere phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc.Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed. INTRODUCTIONGenes for male germ cell development are present on the Ychromosome in different species groups (1–3). In men, theposition of a spermatogenesis locus was mapped in theeuchromatic part of the long Y arm (Yq11). It was called‘azoospermia factor’ (AZF), as the first six men observed withterminal deletions in Yq were azoospermic (4). Mature spermcells were not detectable in their seminal fluid. In all cases, the Ydeletions included the large heterochromatin block of the long Yarm (Yq12) and an undefined amount of the adjacent euchromatin(Yq11). Subsequently, the presence of AZF in Yq11 wasconfirmed by numerous studies at both cytogenetic (5) andmolecular level (6–8). However, the genetic complexity of AZFcould not be revealed by these analyses.This first became possible by the detection of sterile patientswith small interstitial deletions (i.e. microdeletions) in Yq11. Ina study with 13 sterile men suffering from idiopathic azoospermiatwo different microdeletions in Yq11 were observed (9). Theywere mapped to two non overlapping positions in Yq11 interval6 (10). However, further studies of Yq11 microdeletionsassociated to the phenotype of male sterility, only confirmed theposition of an AZF locus in distal Yq11 (11,12). The mostextensive study was performed by Reijo et al. (13) on 89 sterile
1,246 citations
"Genomic heterogeneity and instabili..." refers background in this paper
...E-mail address:petervogt@med.uni-heidelberg.de. mosomes with a ring structure (ring-Y), or translocation the Y to an autosome or the X chromosome, all characte by a complete absence of the fluorescent Y heterochrom in distal Yq (Yq12) were most often reported (Sandberg 1985; Vogt, 1996)....
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...Infertile men with microscopically visible abberratio n Yq11 usually have a mosaic karyotype such as 46,X 45,X0 or 46,X idicY/45,X0, with a variable number 0 cells (Sandberg, 1985; Vogt, 1996; Vogt and Fernan 003)....
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Stanford University1, University of Texas Health Science Center at Houston2, Tel Aviv University3, Pompeu Fabra University4, University of Sassari5, University of Khartoum6, University of the Witwatersrand7, Yale University8, Harvard University9, Wellcome Trust Centre for Human Genetics10, University of Turin11
TL;DR: Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of the authors' species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history.
Abstract: Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history 1 . We used denaturing highperformance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.
959 citations
TL;DR: It is suggested that on the distal portion of the nonfluorescent segment of the long arm of the Y, factors are located controlling spermatogenesis.
Abstract: A deletion of the Y chromosome at the distal portion of band q11 was found in 6 men with normal male habitus but with azoospermia. Five of them were found during a survey of 1170 subfertile males while the sixth was karyotyped because of slight bone abnormalities. These findings, together with a review of the literature, suggest that on the distal portion of the nonfluorescent segment of the long arm of the Y, factors are located controlling spermatogenesis.
926 citations
TL;DR: The availability of the near-complete chromosome sequence, plus many new polymorphisms, a highly resolved phylogeny and insights into its mutation processes, now provide new avenues for investigating human evolution.
Abstract: Until recently, the Y chromosome seemed to fulfil the role of juvenile delinquent among human chromosomes — rich in junk, poor in useful attributes, reluctant to socialize with its neighbours and with an inescapable tendency to degenerate. The availability of the near-complete chromosome sequence, plus many new polymorphisms, a highly resolved phylogeny and insights into its mutation processes, now provide new avenues for investigating human evolution. Y-chromosome research is growing up.
917 citations
"Genomic heterogeneity and instabili..." refers background in this paper
...They have inevitably led o new speculations about the evolutionary future of this ale-specific chromosome (Jobling and Tyler-Smith, 2003) ut also to an increased understanding of the azoospermia actor (AZF) locus in Yq11 concerning its function in uman spermatogenesis....
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...It might be found in men of Y lineage O; a sister clade to N in the current Y phylogeny (Jobling and Tyler-Smith, 2003)....
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