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Comment |
Genes preferentially expressed in bovine oocytes revealed by subtractive and suppressive hybridization. Pennetier S et al. (2006) To isolate bovine oocyte marker genes, we performed suppressive and subtractive hybridization between oocytes and somatic tissues (i.e., intestine, lung, muscle, and cumulus cells). The subtracted library was characterized by sequencing 185 random clone inserts, representing 146 nonredundant genes. After Blast analysis within GenBank, 64% could be identified, 21% were homologous to unannotated expressed sequence tag (EST) or genomic sequences, and 15% were novel. Of 768 clone inserts submitted for differential screening by macroarray hybridization, 83% displayed a fourfold overexpression in the oocyte. The 40 most preferential nonredundant ESTs were submitted to GenBank analysis. Several well-known oocyte-specific genes were represented, including growth differentiation factor 9, bone morphogenetic protein 15, or the zona pellucida glycoprotein genes. Other ESTs were not identified. We investigated the expression profile of several candidates in the oocyte and a panel of gonadal and somatic tissues by reverse transcription-polymerase chain reaction. B-cell translocation gene 4, cullin 1, MCF.2 transforming sequence, a locus similar to snail soma ferritin, and three unidentified genes were, indeed, preferentially expressed in the oocyte, even though most were also highly expressed in testis. The transcripts were degraded throughout preimplantation development and were not compensated for by embryonic transcription after the morula stage. These profiles suggest a role in gametogenesis, fertilization, or early embryonic development.//////////////////
Genomewide discovery and classification of candidate ovarian fertility genes in the mouse. Gallardo TD et al. Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, approximately 1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility. This is an oocyte-specific gene.
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Mutations |
1 mutations
Species: human
Mutation name:
type: naturally occurring
fertility: infertile - ovarian defect
Comment: Homozygous Mutations in BTG4 Cause Zygotic Cleavage Failure and Female Infertility. Zheng W et al. (2020) Zygotic cleavage failure (ZCF) is a unique early embryonic phenotype resulting in female infertility and recurrent failure of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). With this phenotype, morphologically normal oocytes can be retrieved and successfully fertilized, but they fail to undergo cleavage. Until now, whether this phenotype has a Mendelian inheritance pattern and which underlying genetic factors play a role in its development remained to be elucidated. B cell translocation gene 4 (BTG4) is a key adaptor of the CCR4-NOT deadenylase complex, which is involved in maternal mRNA decay in mice, but no human diseases caused by mutations in BTG4 have previously been reported. Here, we identified four homozygous mutations in BTG4 (GenBank: NM_017589.4) that are responsible for the phenotype of ZCF, and we found they followed a recessive inheritance pattern. Three of them-c.73C>T (p.Gln25Ter), c.1A>G (p.?), and c.475_478del (p.Ile159LeufsTer15)-resulted in complete loss of full-length BTG4 protein. For c.166G>A (p.Ala56Thr), although the protein level and distribution of mutant BTG4 was not altered in zygotes from affected individuals or in HeLa cells, the interaction between BTG4 and CNOT7 was abolished. In vivo studies further demonstrated that the process of maternal mRNA decay was disrupted in the zygotes of the affected individuals, which provides a mechanistic explanation for the phenotype of ZCF. Thus, we provide evidence that ZCF is a Mendelian phenotype resulting from mutations in BTG4. These findings contribute to our understanding of the role of BTG4 in human early embryonic development and provide a genetic marker for female infertility.//////////////////
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