Paternal Inheritance Research Articles

Pochodzenie Prusów Szczurowskich

The Szczurowski clan of Szczurowo in the parish of Pniewnik in the Livland belongs to the Prus heraldic clan which is reliably confirmed by documents from the 15th and 16th centuries. The forefather of the Szczurowskis – Andrzej of Szczurowo – came from the Zakroczym County in the Zakroczym Land to the Liv Land in AD 1431. The name of Szczurowo was brought with him from the Zakroczym Land. The place of origin of his ancestors is uncertain, but there is some basis to believe that they came to the Zakroczym Land from the Grójec County in the Czersk Land. Probably in this area the forefathers of the Prus heraldic clan received first feoffments in the second half of the 13th century. They were Old Prussian refugees and they were named in the chivalric privilege of the dukes of Mazovia in AD 1345. It is impossible to determine the exact moment when the Prus heraldic clan forefathers came to Mazovia. Nonetheless, it is rationally justified to believe that it took place in the late sixties or the early seventies of the 13th century and was related to the Great Prussian Uprising against the Teutonic Order here is no certainty about which Old Prussian land is the place of origin of the Prus clan forefathers but we can be sure that they came to Mazovia and then scattered across the Polish-Lithuanian Commonwealth. The source documents analysis and application of the name criterion (paternal names inheritance) lead to the conclu�sion that the heirs of Szczurowo and probably related to them the heirs of Gościeńczyce are directly descended from Old Prussian knights named in the chivalric privilege of AD 1345. It is possible that they were related to 13th century Old Prussians from Pomesania and perhaps came from Sambia. Therefore, we can propose a cautious hypothesis that Sambia was the place of origin of the Prus heraldic clan forefathers

Field-based artificial crossings indicate partial compatibility of reciprocal crosses between Pinus sylvestris and Pinus mugo and unexpected chloroplast DNA inheritance

Crossability relationships between Scots pine (Pinus sylvestris L.) and mountain dwarf pine (Pinus mugo Turra) was studied, using artificial pollination approach. Partial compatibility of the reciprocal crossings of these species was proved experimentally, validating the idea of a spontaneous formation of their hybrid swarms under natural conditions. The hybrids were validated using organellar DNA markers and nuclear DNA microsatellites. Based on the percentage of filled seeds, the interspecific crossings were less efficient than the intraspecific cross-pollinations of P. sylvestris and P. mugo individuals. Both species were found to intercross readily with individuals of their putative hybrid swarm, P. mugo exhibiting a higher hybridological affinity towards putatively hybrid individuals than P. sylvestris. Validation of the hybrids confirmed the paternal inheritance of chloroplast DNA (cpDNA) in the combination P. sylvestris × P. mugo only. Surprisingly, in the reciprocal crossing P. mugo × P. sylvestris, maternal inheritance of cpDNA was revealed. Obtained results offer a new insight into the direction and intensity of gene flow within the hybrid swarms of Scots pine and mountain dwarf pine.

Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity.

Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.

Early onset androgenetic alopecia in men and associated risk factors: a hospital based study

<p class="abstract"><strong>Background:</strong> Androgenetic alopecia (AGA) is the most common form of hair loss affecting up to 80% of the men. It manifests mostly after puberty and is evident by the age of 30. Nowadays the onset of AGA is much earlier and most of them develop AGA in early twenties. Risk factors such as smoking, alcohol consumption and prevalence of AGA in the family are considered to contribute to the early onset. Aims: To estimate the prevalence of and to determine risk factors for AGA in adult males.</p><p class="abstract"><strong>Methods:</strong> A total of 103 patients above 18 years of age attending the dermatology OPD were included in the study. Epidemiological data was collected using a standard questionnaire.<strong></strong></p><p class="abstract"><strong>Results:</strong> In the study population, 68% patients were in the age group 21-30 years. No association was noted between smoking and the age of onset of AGA. An early age of onset was associated in patients with history of alcohol consumption (73.3%). Prevalence of familial AGA was seen in 68% and had a paternal inheritance (62.8%) more than maternal (8.6%). Associated systemic diseases were seen in 12.6% of the patients and hypertension was the most common.</p><p><strong>Conclusions:</strong> AGA is a very common presenting complaint in the younger population. The early onset of AGA itself causes anxiety and apprehension in the patients that further contribute to the hair loss. The presence of a family history in the patients’ needs for an early management of the disorder. Environmental factors like smoking and alcohol consumption thought to play a role in the aetiology of the disease. </p>

“An Ancient Celtic world had filled the air”: the Celtic turn in Louis MacNeice’s mid-century radio writing

This article focuses on the specific meanings and figurations of Celtic identity, myth and history in three works by Louis MacNeice: his long poem Autumn Sequel (1954), written for broadcast on the BBC, and his two late radio plays They Met on Good Friday (1959) and The Mad Islands (1961). It will demonstrate that the poet moves from expressing an archaic and insipidly romanticised form of Celticity in Autumn Sequel, to depicting a significantly more sophisticated Celtic character and identity in They Met on Good Friday and The Mad Islands; both dramas, it will be argued, are informed by a more thoroughly archipelagic conception of cultural formation and identity in the British and Irish isles. In all three texts, MacNeice’s radiogenic engagement with Celtic material functions as a means of interrogating, though not always successfully, the forms and potentialities of human agency, community, and artistic activity within a post-war climate of political disenchantment, social fragmentation and perceived cultural vacuity. The essay will also demonstrate that MacNeice’s Celtic themed radio writing is an important aspect of the poet’s lifelong exploration of his psycho-cultural genealogy and a means of further clarifying his complex maternal and paternal inheritance.

Environmentally Induced Paternal Epigenetic Inheritance and Its Effects on Offspring Health

Increasing evidences indicate that chronic diseases in offspring may be the result of ancestral environmental exposures. Exposures to environmental compounds in windows of epigenetic susceptibility have been shown to promote epigenetic alterations that can be inherited between generations. DNA methylation, histone modifications, and noncoding RNAs are sound mechanistic candidates for the delivery of environmental information from gametes to zygotes. This review focuses mainly on paternal exposures and assesses the risk of epigenetic alterations in the development of diseases, providing insights into relationships between aberrant sperm epigenetic patterns and offspring health. Elucidation of the mechanisms underlying environmental epigenetic information that survive from epigenetic reprogramming and its transmission to future generations may hold a great promise for providing therapeutic targets for epigenetic diseases associated with environmental exposures.

Parent of Origin and Prognosis in Familial Breast Cancer in Sweden.

It has been suggested that prognosis in familial breast cancer could be influenced by the parent of origin, with a worse prognosis when inherited paternally. This study aimed to investigate the effect of the parent of origin on prognosis. Index patients were divided into two study groups depending on the parent of origin. Tumour characteristics and survival data for index patients were collected. In total, 319 families fulfilled the inclusion criteria. No significant difference in overall or recurrence-free survival between those with maternal and those with paternal inheritance was observed, with hazard ratios (HR) of 0.99 (95% confidence interval (CI)=0.54 to 1.80, p=0.97) and 1.22 (95% CI=0.78 to 1.92, p=0.38), respectively. We found no evidence for a worse prognosis in patients with paternally inherited breast cancer. However, only large differences in prognosis were excluded and the tendency for worse recurrence-free survival in the group with paternal inheritance therefore merits further study.

Characterization of the HLA-DR\u03b21 third hypervariable region amino acid sequence according to charge and parental inheritance in systemic sclerosis

BackgroundSpecific HLA class II alleles are associated with systemic sclerosis (SSc) risk, clinical characteristics, and autoantibodies. HLA nomenclature initially developed with antibodies as typing reagents defining DRB1 allele groups. However, alleles from different DRB1 allele groups encode the same third hypervariable region (3rd HVR) sequence, the primary T-cell recognition site, and 3rd HVR charge differences can affect interactions with T cells. We considered 3rd HVR sequences (amino acids 67–74) irrespective of the allele group and analyzed parental inheritance considered according to the 3rd HVR charge, comparing SSc patients with controls.MethodsIn total, 306 families (121 SSc and 185 controls) were HLA genotyped and parental HLA-haplotype origin was determined. Analysis was conducted according to DRβ1 3rd HVR sequence, charge, and parental inheritance.ResultsThe distribution of 3rd HVR sequences differed in SSc patients versus controls (p = 0.007), primarily due to an increase of specific DRB1*11 alleles, in accord with previous observations. The 3rd HVR sequences were next analyzed according to charge and parental inheritance. Paternal transmission of DRB1 alleles encoding a +2 charge 3rd HVR was significantly reduced in SSc patients compared with maternal transmission (p = 0.0003, corrected for analysis of four charge categories p = 0.001). To a lesser extent, paternal transmission was increased when charge was 0 (p = 0.021, corrected for multiple comparisons p = 0.084). In contrast, paternal versus maternal inheritance was similar in controls.ConclusionsSSc patients differed from controls when DRB1 alleles were categorized according to 3rd HVR sequences. Skewed parental inheritance was observed in SSc patients but not in controls when the DRβ1 3rd HVR was considered according to charge. These observations suggest that epigenetic modulation of HLA merits investigation in SSc.

CpG Methylation, a Parent-of-Origin Effect for Maternal-Biased Transmission of Congenital Myotonic Dystrophy

CTG repeat expansions in DMPK cause myotonic dystrophy (DM1) with a continuum of severity and ages of onset. Congenital DM1 (CDM1), the most severe form, presents distinct clinical features, large expansions, and almost exclusive maternal transmission. The correlation between CDM1 and expansion size is not absolute, suggesting contributions of other factors. We determined CpG methylation flanking the CTG repeat in 79 blood samples from 20 CDM1-affected individuals; 21, 27, and 11 individuals with DM1 but not CDM1 (henceforth non-CDM1) with maternal, paternal, and unknown inheritance; and collections of maternally and paternally derived chorionic villus samples (7 CVSs) and human embryonic stem cells (4 hESCs). All but two CDM1-affected individuals showed high levels of methylation upstream and downstream of the repeat, greater than non-CDM1 individuals (p = 7.04958 × 10−12). Most non-CDM1 individuals were devoid of methylation, where one in six showed downstream methylation. Only two non-CDM1 individuals showed upstream methylation, and these were maternally derived childhood onset, suggesting a continuum of methylation with age of onset. Only maternally derived hESCs and CVSs showed upstream methylation. In contrast, paternally derived samples (27 blood samples, 3 CVSs, and 2 hESCs) never showed upstream methylation. CTG tract length did not strictly correlate with CDM1 or methylation. Thus, methylation patterns flanking the CTG repeat are stronger indicators of CDM1 than repeat size. Spermatogonia with upstream methylation may not survive due to methylation-induced reduced expression of the adjacent SIX5, thereby protecting DM1-affected fathers from having CDM1-affected children. Thus, DMPK methylation may account for the maternal bias for CDM1 transmission, larger maternal CTG expansions, age of onset, and clinical continuum, and may serve as a diagnostic indicator.

Chromosome choice for initiation of V-(D)-J recombination is not governed by genomic imprinting.

V-(D)-J recombination generates the antigen receptor diversity necessary for immune cell function while allelic exclusion ensures that each cell expresses a single antigen-receptor. V-(D)-J recombination of the Ig, Tcrb, Tcrg, and Tcrd antigen receptor genes is ordered and sequential so that only one allele generates a productive rearrangement. The mechanism controlling sequential rearrangement of antigen receptor genes, in particular, how only one allele is selected to initiate recombination while at least temporarily leaving the other intact remains unresolved. Genomic imprinting, a widespread phenomenon wherein maternal or paternal allele inheritance determines allele activity, could represent a regulatory mechanism for controlling sequential V-(D)-J rearrangement. We used strain-specific single nucleotide polymorphisms (SNPs) within antigen receptor genes to determine if maternal vs. paternal inheritance could underlie chromosomal choice for the initiation of recombination. We found no parental chromosomal bias in the initiation of V-(D)-J recombination in T or B cells, eliminating genomic imprinting as a potential regulator for this tightly regulated process.

Who's your daddy?: paternal inheritance of metabolic disease risk.

Although the importance of optimizing mothers' health prior to conception and during pregnancy is now well accepted, recent data also implicate health and nutritional status of fathers as contributors to chronic disease risk in their progeny. This brief review will highlight recent epidemiological and experimental studies linking paternal overnutrition, undernutrition, and other forms of stress, to metabolic disease in the offspring. The past 2 years have brought tremendous insights into the mechanisms by which paternal exposures can contribute to disease susceptibility in the next generation. Recent data, both from humans and experimental models, demonstrate that paternal obesity and undernutrition result in epigenetic reprogramming of male germ cells, notably altered DNA methylation, histone retention, and expression of small noncoding RNAs and transfer RNA fragments. Novel mechanisms have also been identified, such as epididymal transport vesicles, seminal fluid hormones and metabolites, and a unique seminal fluid microbiome. Paternal nutritional and other perturbations are linked to risk of metabolic disease and obesity in offspring. Germ cell-dependent mechanisms have recently been linked to these intergenerational effects. Nongenetic, paternal inheritance of chronic disease has important implications for public health, and may provide novel opportunities for multigenerational disease prevention.

Tonga

Tonga Steven Ratuva (bio) The new government of ‘Akilisi Pōhiva was tested to the limit by a number of political, economic, and policy issues after it came to power as a result of the 2014 election, the second under the amended 2010 constitution. For a reform-oriented government with minimal experience yet loaded with ambition and high expectations from the people, the stark reality of transforming and modernizing a society steeped in conservative traditional values, under the patronage of a monarch and a class of nopili (nobles), was a major challenge. Despite some of the institutional and symbolic reforms of the previous decade, some of the social issues of the previous era remained and frustrated plans for changes. One such issue was that of women’s participation in politics, which is the main focus of this review. Although some progressive changes were made in the 2010 amended constitution, remnants of the traditional patriarchal political culture persisted. For instance, no woman was elected to Parliament in the 2010 and 2014 elections. This may appear ironic because under the cultural practice of vahu, women are traditionally accorded a unique social status within the kinship system, sometimes higher than men. (This is very similar to the Fijian practice of vasu, whereby one’s maternal link is considered special and sometimes more prestigious than one’s paternal inheritance.) However, political power has always been a male enterprise, and before July 2016, when the first woman was elected to Parliament, males made up 100 percent of elected people’s representatives and 100 percent of nobles representatives—a record that placed Tonga at the lowest rung of the parliamentary gender diversity scale in the Pacific. The election of Ms ‘Akosita Lavulavu [End Page 181] after a by-election in July 2016 followed successes by a number of women in the local elections a couple of weeks earlier, a testimony to the intensification of campaigns by local civil society organizations, regional organizations, and international agencies for greater awareness of women’s role in politics. Nevertheless, the path to gender consciousness and empowerment in Tonga has been fraught with challenges as forces of progress and conservatism continue to clash over what is appropriate for Tongan society. The tension between competing cultural and political discourses about gender was starkly manifested when the prime minister proudly told Parliament that his cabinet had agreed to ratify the Convention on the Elimination of all Forms of Discrimination Against Women (cedaw) on 9 March 2015 (see article by Helen Lee, this issue) and that Minister for Internal Affairs Fe‘ao Vakata, whose portfolio included women’s issues, had informed the United Nations in New York about the ratification. What was meant to be a celebrated event turned sour as a clash between supporters and opponents of cedaw erupted immediately after the announcement. Pōhiva’s initiative was not surprising because he had been engaged in regional and international social activism as leader of the Tongan pro-democracy movement. Through this, he was actively involved in issues related to the nuclear-free Pacific, decolonization, human rights, and gender equality, among others. In many ways, these involvements further broadened his political and ideological understanding of democracy and provided an alternative policy prism from that of previous prime ministers who, except for Dr Feleti Sevele, were largely drawn from the monarchical or the nopili class. The proposed ratification of cedaw was against the backdrop of the periodic review of the state of human rights in Tonga by the UN Human Rights Council’s Universal Periodic Review Working Group, completed in January 2013, which was critical of the status of human rights in Tonga (UN ohchr 2013b). When quizzed about gender inequality during an ohchr meeting in Geneva, Lord Vaea, the minister for internal affairs at the time, responded by pointing out the number of women employees in public and private institutions and prosecution of perpetrators of family violence. However, a number of countries were very critical of Tonga for not ratifying cedaw (Fonua 2013). ohchr members recommended that concerted efforts be made to speed up gender equality and domestic violence laws and that ratification of cedaw should be a priority (UN ohchr 2013a). Because of...

Paternal pachytene piRNAs are not required for fertilization, embryonic development and sperm-mediated epigenetic inheritance in mice.

Pachytene piRNAs are MIWI-/MILI-bound small RNAs abundantly expressed in pachytene spermatocytes and round spermatids in adult mouse testes. Miwi knockout (KO) male mice are sterile due to spermiogenic arrest. In Caenorhabditis elegans, sperm-borne piRNAs appear to have an epigenetic role during fertilization and development because progeny of individuals with piRNA-deficient gametes display a progressive loss of fertility after several generations. In mice, it remains unknown whether pachytene piRNA-deficient round spermatids can produce offspring, and whether the progeny of Miwi mutants also exhibits transgenerational, progressive fertility loss. Here, we report that Miwi KO round spermatids could fertilize both wild-type (WT) and Miwi KO oocytes through round spermatid injection, and could produce healthy and fertile offspring despite the global downregulation of both MIWI-/MILI-bound pachytene piRNAs. Progeny of ROSI-derived heterozygotes, both male and female, displayed normal fertility for at least three generations when bred with either WT or Miwi KO females. Our data indicate that aberrant MIWI-/MILI-bound pachytene piRNA profiles in spermatids do not affect fertilization, early embryonic development, or fertility of the offspring, suggesting that pachytene piRNAs might not be required for paternal transgenerational epigenetic inheritance in mice.

Herramientas, útiles del trabajo y capitulaciones matrimoniales en la Castilla rural (La Mancha, ss. XVI-XVII)

El estudio de la cultura material del mundo rural castellano durante la Edad Moderna ha experimentado un notable avance de la mano del análisis de la documentación notarial. La presente contribución analiza la estructura de las haciendas campesinas en el momento en el que se forma un nuevo núcleo familiar y profundiza en el papel que desempeñaron las herramientas y útiles relacionados con el mundo del trabajo. El objetivo es observar si, a través de los contratos nupciales, los contrayentes y sus familias proyectaron en el nuevo hogar un deseo de encuadrarse profesionalmente y de continuar la tradición heredada de los progenitores.

Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene

BackgroundIn 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened...

Round Spermatid Injection Rescues Female Lethality of a Paternally Inherited Xist Deletion in Mouse.

In mouse female preimplantation embryos, the paternal X chromosome (Xp) is silenced by imprinted X chromosome inactivation (iXCI). This requires production of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally inherited X chromosome (Xm) is refractory to activation due to the presence of an imprint. Paternal inheritance of an Xist deletion (XpΔXist) is embryonic lethal to female embryos, due to iXCI abolishment. Here, we circumvented the histone-to-protamine and protamine-to-histone transitions of the paternal genome, by fertilization of oocytes via injection of round spermatids (ROSI). This did not affect initiation of XCI in wild type female embryos. Surprisingly, ROSI using ΔXist round spermatids allowed survival of female embryos. This was accompanied by activation of the intact maternal Xist gene, initiated with delayed kinetics, around the morula stage, resulting in Xm silencing. Maternal Xist gene activation was not observed in ROSI-derived males. In addition, no Xist expression was detected in male and female morulas that developed from oocytes fertilized with mature ΔXist sperm. Finally, the expression of the X-encoded XCI-activator RNF12 was enhanced in both male (wild type) and female (wild type as well as XpΔXist) ROSI derived embryos, compared to in vivo fertilized embryos. Thus, high RNF12 levels may contribute to the specific activation of maternal Xist in XpΔXist female ROSI embryos, but upregulation of additional Xp derived factors and/or the specific epigenetic constitution of the round spermatid-derived Xp are expected to be more critical. These results illustrate the profound impact of a dysregulated paternal epigenome on embryo development, and we propose that mouse ROSI can be used as a model to study the effects of intergenerational inheritance of epigenetic marks.

Genetic characterization of the Asian clam species complex (Corbicula) invasion in the Iberian Peninsula

The Asian clam (Corbicula sp.) is an invasive freshwater bivalve native to Asia, the Middle East, Australia, and Africa. It is now widely distributed around the world producing large ecological and economic impacts. Three well-described invasive lineages form a cryptic species complex with asexual reproduction based on androgenesis. In this study, we collected 175 individuals from different Iberian, European, and North American locations to genetically study Corbicula invasion in the Iberian Peninsula using COI and 28S genes. The use of mitochondrial and nuclear markers allows us to characterize both maternal and paternal inheritance from androgenetic Corbicula locations and to deal with the incongruences caused by egg parasitism. We identified 7 COI and 10 28S haplotypes that grouped individuals within the three invasive Corbicula lineages. Haplotype distribution of mitochondrial and nuclear markers detected genetic divergence between the Ebro Delta location and the rest of Iberian sites, suggesting that at least two invasion episodes occurred in the Iberian Peninsula. Haplotype distribution also suggested secondary contacts between Iberian and other European invaded regions. Additionally, results revealed that nuclear hybridization, a feature more widespread than previously reported, contributes to retain gene diversity in the Corbicula invasion.

Paternal age and diet: The contributions of a father’s experience to susceptibility for post-concussion symptomology

In an attempt to improve current understanding of risk factors that influence individual susceptibility to poor outcomes following mild traumatic brain injury (mTBI) or concussion, this project investigated whether modifications to paternal experiences (Advanced Age (AA) or High-Fat Diet (HFD)) affected offspring susceptibility to behavioral symptomology and changes in gene expression following pediatric concussion in a rodent model. The study demonstrated that paternal treatment prior to conception altered behavioral outcomes and molecular characterization of offspring. Offspring of AA fathers demonstrated abnormal behavioral performance when compared to offspring of control fathers. Similarly, paternal HFD altered pathophysiological outcomes for offspring, contributing to the heterogeneity in post-concussion syndrome. Additionally, this study provided insight into the mechanisms that mediate non-genetic paternal inheritance. Paternal treatment and the mTBI significantly influenced expression of a majority of the genes under examination in the prefrontal cortex, hippocampus, and nucleus accumbens, with changes being dependent upon sex and the brain region examined. These epigenetic changes may have contributed to the differences in offspring susceptibility to concussion.

The clinical course of hereditary pancreatitis in children – A comprehensive analysis of 41 cases

BackgroundAvailable data from adult patients do not reflect natural course of hereditary pancreatitis (HP) in children. To date, no study has assessed the clinical course of HP in children. ObjectiveTo investigate the clinical course of HP in children and compare it to non-HP group with chronic pancreatitis (CP). MethodsA group of 265 children with CP, hospitalized from 1988 to 2014, were enrolled in the study. Medical records of those patients were reviewed for data on presentation, diagnostic findings and treatment. All children were screened for mutations in major pancreatitis-associated genes, i.e. PRSS1, SPINK1, and CFTR. ResultsHP was diagnosed in 41 children (15.5%). Family history was positive in 88% of children with HP. Mutations of PRSS1 gene were found in 80% (33/41) of HP patients. We detected p.R122H, p.R122C, p.N29I, and p.E79K mutation in 34% (14/41), 27% (11/41), 12% (5/41), and 7% (3/41) of HP patients, respectively. Patients with paternal inheritance had first symptoms earlier than those with maternal inheritance (5.9 vs. 9.1 years; P < 0.05). Children with HP showed more severe changes in ERCP then those from non-HP group (2.05 Cambridge grade, vs. 1.6°; P < 0.05). ESWL was performed more frequently in HP group (12.2% vs. 3.1%; P < 0.05). There was no difference in age of disease onset (7.98 vs. 8.9 years; NS), pancreatic duct stenting (46.3% vs. 33%; NS), or number of surgical interventions (12.2% vs. 14.3%; NS) between both groups. ConclusionsChildren with HP reveal significantly more severe clinical presentation of the disease than non-HP patients, despite the same age of onset.

Mitochondrial selfish elements and the evolution of biological novelties.

We report the present knowledge about RPHM21, a novel male-specific mitochondrial protein with a putative role in the paternal inheritance of sperm mitochondria in the Manila clam Ruditapes philippinarum, a species with doubly uniparental inheritance of mitochondria (DUI). We review all the available data on rphm21 transcription and translation, analyze in detail its female counterpart, RPHF22, discuss the homology with RPHM21, the putative function and origin, and analyze their polymorphism. The available evidence is compatible with a viral origin of RPHM21 and supports its activity during spermatogenesis. RPHM21 is progressively accumulated in mitochondria and nuclei of spermatogenic cells, and we hypothesize it can influence mitochondrial inheritance and sexual differentiation. We propose a testable model that describes how the acquisition of selfish features by a mitochondrial lineage might have been responsible for the emergence of DUI, and for the evolution of separate sexes (gonochorism) from hermaphroditism. The appearance of DUI most likely entailed the invasion of at least 1 selfish element, and the extant DUI systems can be seen as resolved conflicts. It was proposed that hermaphroditism was the ancestral condition of bivalves, and a correlation between DUI and gonochorism was documented. We hypothesize that DUI might have driven the shift from hermaphroditism to gonochorism, with androdioecy as transition state. The invasion of sex-ratio distorters and the evolution of suppressors can prompt rapid changes among sex-determination mechanisms, and DUI might have been responsible for one of such changes in some bivalve species. If true, DUI would represent the first animal sex-determination system involving mtDNA-encoded proteins.