Cromatina espermática: quebrando paradigmas / Sperm chromatin: breaking paradigms

Há algumas décadas, pensava-se que espermatozoides maduros possuíssem uma cromatina não funcional, inerte, sem a capacidade de transcrição. Acreditava-se que a matriz nuclear não existisse e que a presença de histonas no núcleo seria um erro no processo de compactação cromatínica, o que poderia interferir na fertilidade do macho. Hoje se sabe que, entre as estruturas toroidais, unidades básicas da cromatina espermática altamente compactada, há algumas poucas regiões que contêm sequências de nucleossomos, e estas geralmente estão anexadas a uma matriz nuclear proteica. Os espermatozoides possuem cromatina altamente organizada e são condutores metabolicamente funcionais do genoma masculino, carreando RNAs de diferentes tipos, os quais, tanto quanto os nucleossomos, são importantes sinalizadores epigenéticos paternos e, logo,influenciam o desenvolvimento embrionário inicial. Portanto, alterações cromatínicas podem não somente interferir no processo de fecundação, como principalmente no desenvolvimento embrionário, o que reforça a necessidade da análise da cromatina na avaliação de reprodutores machos.

Decades ago, it was thought thatspermatozoa had a chromatin nonfunctional, inert, without the abilityto transcription. It was believed in the absence of nuclear matrix and the presence of the core histones would be an error in the chromatin packaging, which could interfere with male fertility. Today we know that between thetoroidal structures, basic units of highly compacted sperm chromatin, there are a few regions containing nucleosome sequences, these usually being attached to a nuclear protein matrix. The sperm chromatin is highly organized and is metabolically functional carrier of male genome, carrying different RNA types, which, along with the nucleosomes are important paternal epigenetic signaling, and influencing early embryonic development. Therefore, chromatin alterations not only interfere with the fertilization process, but also influencethe embryonic development, which reinforces the need for chromatin analysis in the evaluation of breeding males.

Cromatina espermática: quebrando paradigmas / Sperm chromatin: breaking paradigms

Há algumas décadas, pensava-se que espermatozoides maduros possuíssem uma cromatina não funcional, inerte, sem a capacidade de transcrição. Acreditava-se que a matriz nuclear não existisse e que a presença de histonas no núcleo seria um erro no processo de compactação cromatínica, o que poderia interferir na fertilidade do macho. Hoje se sabe que, entre as estruturas toroidais, unidades básicas da cromatina espermática altamente compactada, há algumas poucas regiões que contêm sequências de nucleossomos, e estas geralmente estão anexadas a uma matriz nuclear proteica. Os espermatozoides possuem cromatina altamente organizada e são condutores metabolicamente funcionais do genoma masculino, carreando RNAs de diferentes tipos, os quais, tanto quanto os nucleossomos, são importantes sinalizadores epigenéticos paternos e, logo,influenciam o desenvolvimento embrionário inicial. Portanto, alterações cromatínicas podem não somente interferir no processo de fecundação, como principalmente no desenvolvimento embrionário, o que reforça a necessidade da análise da cromatina na avaliação de reprodutores machos.(AU)

Decades ago, it was thought thatspermatozoa had a chromatin nonfunctional, inert, without the abilityto transcription. It was believed in the absence of nuclear matrix and the presence of the core histones would be an error in the chromatin packaging, which could interfere with male fertility. Today we know that between thetoroidal structures, basic units of highly compacted sperm chromatin, there are a few regions containing nucleosome sequences, these usually being attached to a nuclear protein matrix. The sperm chromatin is highly organized and is metabolically functional carrier of male genome, carrying different RNA types, which, along with the nucleosomes are important paternal epigenetic signaling, and influencing early embryonic development. Therefore, chromatin alterations not only interfere with the fertilization process, but also influencethe embryonic development, which reinforces the need for chromatin analysis in the evaluation of breeding males.(AU)

Wiskott-Aldrich syndrome in a family with Fanconi anemia.

Thrombocytopenia may be the presenting finding for both Wiskott-Aldrich syndrome and Fanconi anemia. We examined a sibship of four boys who had features of both of these hematologic disorders. Peripheral blood lymphocytes from three of the boys demonstrated DNA instability when cultured with diepoxybutane, confirming the diagnosis of Fanconi anemia in these patients. However, results of linkage analysis and X chromosome inactivation studies were consistent with the diagnosis of Wiskott-Aldrich syndrome in two of the boys, including one of the boys with Fanconi anemia. These findings could be attributed to the occurrence of two rare genetic disorders in a single family or to an unusual variant of Fanconi anemia. The recent identification of the Wiskott-Aldrich gene permitted us to address this question directly. Epstein-Barr virus-transformed cell lines from the two boys thought to have Wiskott-Aldrich syndrome on the basis of linkage analysis failed to express transcripts for the Wiskott-Aldrich gene. Genomic DNA from these two patients demonstrated a G insertion in the tenth exon of the Wiskott-Aldrich gene, resulting in a frameshift and a premature stop codon. Surprisingly, the patient with Fanconi anemia and a null mutation in the Wiskott-Aldrich gene had typical Fanconi anemia but mild Wiskott-Aldrich syndrome.

Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene.

The Wiskott-Aldrich syndrome (WAS) is characterized by defective platelet and lymphocyte function associated with eczema and increased susceptibility to malignancies. It is caused by mutations of the WAS protein-encoding gene (WASP). X-lined thrombocytopenia, defined by low platelet counts and volume, may be an allelic variant of WAS. In patients with XLT from two unrelated families, WASP gene defects were identified by single-strand conformational polymorphism and by sequencing. Point mutations in exon 2 of the WASP gene were found in the patients from both families in which XLT segregated. Several obligate heterozygote female members of these families display a random pattern of X inactivation in their peripheral blood leukocytes. This study shows that XLT may be caused by mutations of the WASP, thus representing an allelic variant of WAS.