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Renee Reijo - One of the best experts on this subject based on the ideXlab platform.
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the daz gene cluster on the human y chromosome arose from an autosomal gene that was transposed repeatedly amplified and pruned
Nature Genetics, 1996Co-Authors: Richa Saxena, Renee Reijo, Raaji Alagappan, Helen Skaletsky, Steve Rozen, Laura G Brown, Trevor Hawkins, Mary Pat Reeve, Mary Beth Dinulos, Christine M DistecheAbstract:It is widely believed that most or all Y–chromosomal genes were once shared with the X chromosome. The DAZ gene is a candidate for the human Y–chromosomal Azoospermia Factor (AZF). We report multiple copies of DAZ (>99% identical in DNA sequence) clustered in the AZF region and a functional DAZ homologue (DAZH) on human chromosome 3. The entire gene family appears to be expressed in germ cells. Sequence analysis indicates that the Y–chromosomal DAZ cluster arose during primate evolution by (i) transposing the autosomal gene to the Y, (ii) amplifying and pruning exons within the transposed gene and (iii) amplifying the modified gene. These results challenge prevailing views of sex chromosome evolution, suggesting that acquisition of autosomal fertility genes is an important process in Y chromosome evolution.
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severe oligozoospermia resulting from deletions of Azoospermia Factor gene on y chromosome
The Lancet, 1996Co-Authors: Renee Reijo, Raaji Alagappan, Piera Patrizio, David L. PageAbstract:Abstract Summary Background About 13% of cases of non-obstructive Azoospermia are caused by deletion of the Azoospermia Factor ( AZF ), a gene or gene complex normally located on the long arm of the Y chromosome. Oligozoospermia is far more common than Azoospermia, but little is known about genetic causes. We investigated whether severe oligozoospermia is caused by AZF deletions and, if so, whether those deletions are present in mature spermatozoa. Methods By PCR, we tested leucocyte DNA, from 35 men who presented at infertility clinics and who had severe oligozoospermia, for the presence of 118 DNA landmarks scattered across the Y chromosome. In the two men in whom Y-chromosome deletions in leucocyte DNA were detected, we also tested leucocyte DNA from the individuals' fathers, and in one man we tested sperm DNA. Findings In two men with ejaculate sperm counts of 40 000-100 000 per mL, we detected Y-chromosome deletions in leucocyte DNA similar in location to those previously reported in azoospermic individuals. No Y-chromosome deletions were detected in the fathers of the two men. For one of the two men, sperm DNA was tested, and it showed the same Y-chromosome deletion seen in leucocytes. Interpretation The Y-chromosome deletions in these two men are de-novo mutations, and are therefore the cause of their severe oligozoospermia. Not only is the absence of AZF compatible with spermatogenesis, albeit at reduced rate, but also the resultant sperm bear the mutant Y chromosome. Because intracytoplasmic sperm injection is increasingly used as a means of circumventing oligozoospermia, AZF deletions could be transmitted by this practice, and would probably result in infertile sons. In cases of severe oligozoospermia, it may be appropriate to offer Y-DNA testing and genetic counselling before starting assisted reproductive procedures.
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diverse spermatogenic defects in humans caused by y chromosome deletions encompassing a novel rna binding protein gene
Human Reproduction, 1996Co-Authors: Renee Reijo, Raaji Alagappan, Steve Rozen, Laura G Brown, Pia Salo, M J Rosenberg, Tom Jaffe, Donald Straus, Outi Hovatta, Albert De La ChapelleAbstract:We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with Azoospermia (no spermatozoa in their semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from the complete absence of germ cells to spermatogenic arrest with the occasional production of condensed spermatids. We found no evidence of YRRM genes, recently proposed as AZF candidates in the AZF region. The region contains a single-copy gene, DAZ (deleted in Azoospermia), which is transcribed in the adult testis and appears to encode an RNA-binding protein. The possibility that DAZ is AZF should now be explored.
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diverse spermatogenic defects in humans caused by y chromosome deletions encompassing a novel rna binding protein gene
Nature Genetics, 1995Co-Authors: Renee Reijo, Raaji Alagappan, Steve Rozen, Laura G Brown, Pia Salo, M J Rosenberg, Tom Jaffe, Donald Straus, Outi HovattaAbstract:We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with Azoospermia (no sperm in semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from complete absence of germ cells to spermatogenic arrest with occasional production of condensed spermatids. We find no evidence of YRRM genes, recently proposed as AZF candidates, in the AZF region. The region contains a single–copy gene, DAZ (Deleted in Azoospermia), which is transcribed in the adult testis and appears to encode an RNA binding protein. The possibility that DAZ is AZF should now be explored.
Raaji Alagappan - One of the best experts on this subject based on the ideXlab platform.
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the daz gene cluster on the human y chromosome arose from an autosomal gene that was transposed repeatedly amplified and pruned
Nature Genetics, 1996Co-Authors: Richa Saxena, Renee Reijo, Raaji Alagappan, Helen Skaletsky, Steve Rozen, Laura G Brown, Trevor Hawkins, Mary Pat Reeve, Mary Beth Dinulos, Christine M DistecheAbstract:It is widely believed that most or all Y–chromosomal genes were once shared with the X chromosome. The DAZ gene is a candidate for the human Y–chromosomal Azoospermia Factor (AZF). We report multiple copies of DAZ (>99% identical in DNA sequence) clustered in the AZF region and a functional DAZ homologue (DAZH) on human chromosome 3. The entire gene family appears to be expressed in germ cells. Sequence analysis indicates that the Y–chromosomal DAZ cluster arose during primate evolution by (i) transposing the autosomal gene to the Y, (ii) amplifying and pruning exons within the transposed gene and (iii) amplifying the modified gene. These results challenge prevailing views of sex chromosome evolution, suggesting that acquisition of autosomal fertility genes is an important process in Y chromosome evolution.
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severe oligozoospermia resulting from deletions of Azoospermia Factor gene on y chromosome
The Lancet, 1996Co-Authors: Renee Reijo, Raaji Alagappan, Piera Patrizio, David L. PageAbstract:Abstract Summary Background About 13% of cases of non-obstructive Azoospermia are caused by deletion of the Azoospermia Factor ( AZF ), a gene or gene complex normally located on the long arm of the Y chromosome. Oligozoospermia is far more common than Azoospermia, but little is known about genetic causes. We investigated whether severe oligozoospermia is caused by AZF deletions and, if so, whether those deletions are present in mature spermatozoa. Methods By PCR, we tested leucocyte DNA, from 35 men who presented at infertility clinics and who had severe oligozoospermia, for the presence of 118 DNA landmarks scattered across the Y chromosome. In the two men in whom Y-chromosome deletions in leucocyte DNA were detected, we also tested leucocyte DNA from the individuals' fathers, and in one man we tested sperm DNA. Findings In two men with ejaculate sperm counts of 40 000-100 000 per mL, we detected Y-chromosome deletions in leucocyte DNA similar in location to those previously reported in azoospermic individuals. No Y-chromosome deletions were detected in the fathers of the two men. For one of the two men, sperm DNA was tested, and it showed the same Y-chromosome deletion seen in leucocytes. Interpretation The Y-chromosome deletions in these two men are de-novo mutations, and are therefore the cause of their severe oligozoospermia. Not only is the absence of AZF compatible with spermatogenesis, albeit at reduced rate, but also the resultant sperm bear the mutant Y chromosome. Because intracytoplasmic sperm injection is increasingly used as a means of circumventing oligozoospermia, AZF deletions could be transmitted by this practice, and would probably result in infertile sons. In cases of severe oligozoospermia, it may be appropriate to offer Y-DNA testing and genetic counselling before starting assisted reproductive procedures.
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diverse spermatogenic defects in humans caused by y chromosome deletions encompassing a novel rna binding protein gene
Human Reproduction, 1996Co-Authors: Renee Reijo, Raaji Alagappan, Steve Rozen, Laura G Brown, Pia Salo, M J Rosenberg, Tom Jaffe, Donald Straus, Outi Hovatta, Albert De La ChapelleAbstract:We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with Azoospermia (no spermatozoa in their semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from the complete absence of germ cells to spermatogenic arrest with the occasional production of condensed spermatids. We found no evidence of YRRM genes, recently proposed as AZF candidates in the AZF region. The region contains a single-copy gene, DAZ (deleted in Azoospermia), which is transcribed in the adult testis and appears to encode an RNA-binding protein. The possibility that DAZ is AZF should now be explored.
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diverse spermatogenic defects in humans caused by y chromosome deletions encompassing a novel rna binding protein gene
Nature Genetics, 1995Co-Authors: Renee Reijo, Raaji Alagappan, Steve Rozen, Laura G Brown, Pia Salo, M J Rosenberg, Tom Jaffe, Donald Straus, Outi HovattaAbstract:We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with Azoospermia (no sperm in semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from complete absence of germ cells to spermatogenic arrest with occasional production of condensed spermatids. We find no evidence of YRRM genes, recently proposed as AZF candidates, in the AZF region. The region contains a single–copy gene, DAZ (Deleted in Azoospermia), which is transcribed in the adult testis and appears to encode an RNA binding protein. The possibility that DAZ is AZF should now be explored.
Piera Patrizio - One of the best experts on this subject based on the ideXlab platform.
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severe oligozoospermia resulting from deletions of Azoospermia Factor gene on y chromosome
The Lancet, 1996Co-Authors: Renee Reijo, Raaji Alagappan, Piera Patrizio, David L. PageAbstract:Abstract Summary Background About 13% of cases of non-obstructive Azoospermia are caused by deletion of the Azoospermia Factor ( AZF ), a gene or gene complex normally located on the long arm of the Y chromosome. Oligozoospermia is far more common than Azoospermia, but little is known about genetic causes. We investigated whether severe oligozoospermia is caused by AZF deletions and, if so, whether those deletions are present in mature spermatozoa. Methods By PCR, we tested leucocyte DNA, from 35 men who presented at infertility clinics and who had severe oligozoospermia, for the presence of 118 DNA landmarks scattered across the Y chromosome. In the two men in whom Y-chromosome deletions in leucocyte DNA were detected, we also tested leucocyte DNA from the individuals' fathers, and in one man we tested sperm DNA. Findings In two men with ejaculate sperm counts of 40 000-100 000 per mL, we detected Y-chromosome deletions in leucocyte DNA similar in location to those previously reported in azoospermic individuals. No Y-chromosome deletions were detected in the fathers of the two men. For one of the two men, sperm DNA was tested, and it showed the same Y-chromosome deletion seen in leucocytes. Interpretation The Y-chromosome deletions in these two men are de-novo mutations, and are therefore the cause of their severe oligozoospermia. Not only is the absence of AZF compatible with spermatogenesis, albeit at reduced rate, but also the resultant sperm bear the mutant Y chromosome. Because intracytoplasmic sperm injection is increasingly used as a means of circumventing oligozoospermia, AZF deletions could be transmitted by this practice, and would probably result in infertile sons. In cases of severe oligozoospermia, it may be appropriate to offer Y-DNA testing and genetic counselling before starting assisted reproductive procedures.
Laura G Brown - One of the best experts on this subject based on the ideXlab platform.
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a family of human y chromosomes has dispersed throughout northern eurasia despite a 1 8 mb deletion in the Azoospermia Factor c region
Genomics, 2004Co-Authors: Sjoerd Repping, Robert D Oates, Cindy M Korver, Saskia K M Van Daalen, Laura G Brown, Janet D Marszalek, Judith Gianotten, Sherman J Silber, Fulco Van Der Veen, David C PageAbstract:The human Y chromosome is replete with amplicons—very large, nearly identical repeats—which render it susceptible to interstitial deletions that often cause spermatogenic failure. Here we describe a recurrent, 1.8-Mb deletion that removes half of the Azoospermia Factor c (AZFc) region, including 12 members of eight testis-specific gene families. We show that this ‘‘b2/b3’’ deletion arose at least four times in human history—likely on inverted variants of the AZFc region that we find exist as common polymorphisms. We observed the b2/b3 deletion primarily in one family of closely related Y chromosomes—branch N in the Y-chromosome genealogy—in which all chromosomes carried the deletion. This branch is known to be widely distributed in northern Eurasia, accounts for the majority of Y chromosomes in some populations, and appears to be several thousand years old. The population-genetic success of the b2/b3 deletion is surprising, (i) because it removes half of AZFc and (ii) because the gr/gr deletion, which removes a similar set of testis-specific genes, predisposes to spermatogenic failure. Our present findings suggest either that the b2/b3 deletion has at most a modest effect on fitness or that, within branch N, its effect has been counterbalanced by another genetic, possibly Y-linked, Factor.
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the azfc region of the y chromosome features massive palindromes and uniform recurrent deletions in infertile men
Nature Genetics, 2001Co-Authors: Helen Skaletsky, Laura G Brown, Tomoko Kurodakawaguchi, Patrick Minx, Holland S Cordum, Robert H Waterston, Richard K WilsonAbstract:Deletions of the AZFc (Azoospermia Factor c) region of the Y chromosome are the most common known cause of spermatogenic failure. We determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (massive repeat units) using an iterative mapping‐sequencing process. A complex of three palindromes, the largest spanning 3 Mb with 99.97% identity between its arms, encompasses the AZFc region. The palindromes are constructed from six distinct families of amplicons, with unit lengths of 115‐678 kb, and may have resulted from tandem duplication and inversion during primate evolution. The palindromic complex contains 11 families of transcription units, all expressed in testis. Deletions of AZFc that cause infertility are remarkably uniform, spanning a 3.5-Mb segment and bounded by 229-kb direct repeats that probably served as substrates for homologous recombination.
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the daz gene cluster on the human y chromosome arose from an autosomal gene that was transposed repeatedly amplified and pruned
Nature Genetics, 1996Co-Authors: Richa Saxena, Renee Reijo, Raaji Alagappan, Helen Skaletsky, Steve Rozen, Laura G Brown, Trevor Hawkins, Mary Pat Reeve, Mary Beth Dinulos, Christine M DistecheAbstract:It is widely believed that most or all Y–chromosomal genes were once shared with the X chromosome. The DAZ gene is a candidate for the human Y–chromosomal Azoospermia Factor (AZF). We report multiple copies of DAZ (>99% identical in DNA sequence) clustered in the AZF region and a functional DAZ homologue (DAZH) on human chromosome 3. The entire gene family appears to be expressed in germ cells. Sequence analysis indicates that the Y–chromosomal DAZ cluster arose during primate evolution by (i) transposing the autosomal gene to the Y, (ii) amplifying and pruning exons within the transposed gene and (iii) amplifying the modified gene. These results challenge prevailing views of sex chromosome evolution, suggesting that acquisition of autosomal fertility genes is an important process in Y chromosome evolution.
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diverse spermatogenic defects in humans caused by y chromosome deletions encompassing a novel rna binding protein gene
Human Reproduction, 1996Co-Authors: Renee Reijo, Raaji Alagappan, Steve Rozen, Laura G Brown, Pia Salo, M J Rosenberg, Tom Jaffe, Donald Straus, Outi Hovatta, Albert De La ChapelleAbstract:We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with Azoospermia (no spermatozoa in their semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from the complete absence of germ cells to spermatogenic arrest with the occasional production of condensed spermatids. We found no evidence of YRRM genes, recently proposed as AZF candidates in the AZF region. The region contains a single-copy gene, DAZ (deleted in Azoospermia), which is transcribed in the adult testis and appears to encode an RNA-binding protein. The possibility that DAZ is AZF should now be explored.
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diverse spermatogenic defects in humans caused by y chromosome deletions encompassing a novel rna binding protein gene
Nature Genetics, 1995Co-Authors: Renee Reijo, Raaji Alagappan, Steve Rozen, Laura G Brown, Pia Salo, M J Rosenberg, Tom Jaffe, Donald Straus, Outi HovattaAbstract:We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with Azoospermia (no sperm in semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from complete absence of germ cells to spermatogenic arrest with occasional production of condensed spermatids. We find no evidence of YRRM genes, recently proposed as AZF candidates, in the AZF region. The region contains a single–copy gene, DAZ (Deleted in Azoospermia), which is transcribed in the adult testis and appears to encode an RNA binding protein. The possibility that DAZ is AZF should now be explored.
Steve Rozen - One of the best experts on this subject based on the ideXlab platform.
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deletion of Azoospermia Factor a azfa region of human y chromosome caused by recombination between herv15 proviruses
Human Molecular Genetics, 2000Co-Authors: Helen Skaletsky, Steve Rozen, Jorg Gromoll, Eberhard Nieschlag, Robert D Oates, David L. PageAbstract:Deletion of any of three regions of the human Y chromosome results in spermatogenic failure and infertility. We previously sequenced one of these regions, Azoospermia Factor a (AZFa) and found that it spanned ∼800 kb. By sequence-tagged site (STS) content mapping, we roughly defined deletion breakpoints in two unrelated, azoospermic men with AZFa deletions. The positions of proximal and distal breakpoints were similar in the two men. Hypothesizing that the deletions might have been generated by homologous recombination, we searched electronically for DNA sequence similarities between the proximal and distal breakpoint regions. These comparisons revealed the most striking sequence similarities anywhere along or near the AZFa region. In the proximal breakpoint region, we identified a 10 kb provirus of the recently defined HERV15 class of endogenous retroviruses. In the distal breakpoint region, we found a second HERV15 provirus, 94% identical in DNA sequence to the first and in the same orientation. (A partial LINE insertion in this distal provirus proved to be the basis of the previously described DYS11/ p12f polymorphism.) The AZFa deletions in the two men differed slightly, but all breakpoints fell within the HERV15 proviruses. Indeed, sequencing of deletion junctions from the two men revealed that homologous recombination had occurred within large domains of absolute sequence identity between the proximal and distal proviruses. When combined with published STS mapping data for other AZFa-deleted men, our findings suggest that recombination between these two HERV15 proviruses could account for most AZFa deletions.
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the daz gene cluster on the human y chromosome arose from an autosomal gene that was transposed repeatedly amplified and pruned
Nature Genetics, 1996Co-Authors: Richa Saxena, Renee Reijo, Raaji Alagappan, Helen Skaletsky, Steve Rozen, Laura G Brown, Trevor Hawkins, Mary Pat Reeve, Mary Beth Dinulos, Christine M DistecheAbstract:It is widely believed that most or all Y–chromosomal genes were once shared with the X chromosome. The DAZ gene is a candidate for the human Y–chromosomal Azoospermia Factor (AZF). We report multiple copies of DAZ (>99% identical in DNA sequence) clustered in the AZF region and a functional DAZ homologue (DAZH) on human chromosome 3. The entire gene family appears to be expressed in germ cells. Sequence analysis indicates that the Y–chromosomal DAZ cluster arose during primate evolution by (i) transposing the autosomal gene to the Y, (ii) amplifying and pruning exons within the transposed gene and (iii) amplifying the modified gene. These results challenge prevailing views of sex chromosome evolution, suggesting that acquisition of autosomal fertility genes is an important process in Y chromosome evolution.
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diverse spermatogenic defects in humans caused by y chromosome deletions encompassing a novel rna binding protein gene
Human Reproduction, 1996Co-Authors: Renee Reijo, Raaji Alagappan, Steve Rozen, Laura G Brown, Pia Salo, M J Rosenberg, Tom Jaffe, Donald Straus, Outi Hovatta, Albert De La ChapelleAbstract:We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with Azoospermia (no spermatozoa in their semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from the complete absence of germ cells to spermatogenic arrest with the occasional production of condensed spermatids. We found no evidence of YRRM genes, recently proposed as AZF candidates in the AZF region. The region contains a single-copy gene, DAZ (deleted in Azoospermia), which is transcribed in the adult testis and appears to encode an RNA-binding protein. The possibility that DAZ is AZF should now be explored.
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diverse spermatogenic defects in humans caused by y chromosome deletions encompassing a novel rna binding protein gene
Nature Genetics, 1995Co-Authors: Renee Reijo, Raaji Alagappan, Steve Rozen, Laura G Brown, Pia Salo, M J Rosenberg, Tom Jaffe, Donald Straus, Outi HovattaAbstract:We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with Azoospermia (no sperm in semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the Azoospermia Factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from complete absence of germ cells to spermatogenic arrest with occasional production of condensed spermatids. We find no evidence of YRRM genes, recently proposed as AZF candidates, in the AZF region. The region contains a single–copy gene, DAZ (Deleted in Azoospermia), which is transcribed in the adult testis and appears to encode an RNA binding protein. The possibility that DAZ is AZF should now be explored.
