Identifying the parent-of-origin of de novo SNVs in schizophrenia

Several studies over the last few years have shown that newly arising (de novo) mutations contribute to the genetics of schizophrenia (SZ), autism (ASD) and other developmental disorders. The strongest evidence comes from studies of de novo Copy Number Variation (CNV), where the rate of new mutations is shown to be increased in cases when compared to controls [23, 24]. Research on de novo point mutations and small insertion-deletions (indels) has been more limited, but with the development of next-generation sequencing (NGS) technology, such studies are beginning to provide preliminary evidence that de novo single-nucleotide mutations (SNVs) might also increase risk of SZ and ASD [25, 26] Advanced paternal age is a major source of new mutations in human beings [27] and could thus be associated with increased risk for developing SZ, ASD or other developmental disorders. Indeed, advanced paternal age is found to be a risk factor for developing SZ and ASD in the offspring [28, 29] and new mutations related to advanced paternal age have been implicated as a cause of sporadic cases in several autosomal dominant diseases, some neurodevelopmental diseases, including SZ and ASD, and social functioning. New single-base substitutions occur at higher rates at males compared to females and this difference increases with paternal age. This is due to the fact that sperm cells go through a much higher number of cell divisions (~840 by the age of 50), which increases the risk for DNA copy errors in the male germ line [30] . By contrast, the female eggs (oocytes) undergo only 24 cell divisions and all but the last occur during foetal life. The aim of my project is to determine the parent-of-origin of de novo SNVs, using large samples of parent-offspring trios affected with schizophrenia (SZ). From whole exome sequencing of 618 Bulgarian proband-offspring trios affected, nearly 1000 de novo (SNVs or small indels) have been identified and from these, the parent-of-origin of at least 60% of the mutations (N=600) can be established. This project is contained in a main one that consists on the determination of the parental origin of different types of de novo mutations (SNVs, small indels and large CNVs).

The reproductive cycle of Ophichthus rufus (Pisces: Anguilliformes) in the NW Mediterranean

The reproductive biology of the Mediterranean Snake cel, Ophichthus Rufus (Ophichthidae), was studied on the basis of microscopic and macroscopic analysis. Results show that O.rufus is an oviparous species with a group synchronous ovary type. The maturation process of the gonads starts in December and progress until August, when ovulation and a pawing take place. It is a fractional spawned with buoyant eggs. Potential annual fecundity estimates ranged from 1426 to 23.605 oocytes. Except for small sizes, a clear predominance of females was observed

Sex Reversal in Zebrafish fancl Mutants is Caused by Tp53-Mediated Germ Cell Apoptosis

The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53) mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA-repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination.

Histological Study of the Sex-Change in the Skunk Clownfish Amphiprion akallopisos

Sex change in the protandrous fish Amphiprion akallopisos Bleeker, 1853 (F.Pomacentridae) has been analysed. Experiments consisted of placing males together after being separated from their mates, and observe changes in gonad histology at different periods, in order to identify signs of the sex change process. The presence of a first invagination on the male gonad wall, and the observation of the first cortical alveoli oocytes as an indication of the beginning of the vitellogenesis process, was the first symptom of the sex change, which has been detected after 18 days in one of the males. Period needed for the sex changing process was size independent. The process by which wall invagination is converted into ovarian lumen in the future mature ovary is also described

Health and reproduction of red mullet, Mullus barbatus, in the western Mediterranean Sea

The reproductive and general health of exploited fish stocks is an essential element of sustainable and profitable fisheries. The main purpose of this study was to assess the relationships between reproduction and two important parameters of fish health (parasitism and energy reserves) in female specimens of red mullet, Mullus barbatus, from the western Mediterranean Sea. We present new data for this species on (i) the prevalence and intensity of infection by metazoan parasites; (ii) the total lipid content in muscle and gonads as a measure of condition and (iii) fecundity and egg quality as a measure of their reproductive capacity. The results show that M. barbatus is a batch spawner with an income breeding strategy, an asynchronous development of oocytes and indeterminate fecundity. The results also indicate that the three most abundant and prevalent parasites significantly affect the condition and reproduction of M. barbatus. Specifically, the digenean, Opecoeloides furcatus, causes a reduction in the female"s energy reserves, while the nematodes, Hysterothylacium fabri and H. aduncum, produce a rise in egg production but impair egg quality. These implications of the relationships between parasitism, fish health and fish reproduction should be taken into consideration in the assessment and management of exploited species