Impact of patrilocality on contrasting patterns of paternal and maternal heritage in Central-West Africa.

Despite their ancient past and high diversity, African populations are the least represented in human population genetic studies. In this study, uniparental markers (mtDNA and Y chromosome) were used to investigate the impact of sociocultural factors on the genetic diversity and inter-ethnolinguistic gene flow in the three major Nigerian groups: Hausa (n = 89), Yoruba (n = 135) and Igbo (n = 134). The results show a distinct history from the maternal and paternal perspectives. The three Nigerian groups present a similar substrate for mtDNA, but not for the Y chromosome. The two Niger-Congo groups, Yoruba and Igbo, are paternally genetically correlated with populations from the same ethnolinguistic affiliation. Meanwhile, the Hausa is paternally closer to other Afro-Asiatic populations and presented a high diversity of lineages from across Africa. When expanding the analyses to other African populations, it is observed that language did not act as a major barrier to female-mediated gene flow and that the differentiation of paternal lineages is better correlated with linguistic than geographic distances. The results obtained demonstrate the impact of patrilocality, a common and well-established practice in populations from Central-West Africa, in the preservation of the patrilineage gene pool and in the affirmation of identity between groups.

Fathering children aged from 2 to 10: psychometric properties of the IFI-BR-27 / Paternidade com filhos entre 2 e 10 anos de idade: propriedades psicométricas do IFI-BR-27 / Paternidad con hijos de entre 2 y 10 años: propiedades psicométricas del IFI-BR-27

The Inventory of Father Involvement (IFI) was developed to examine paternal involvement among men with children from 5 to 10 years of age. However, father involvement affects child development starting in the child's infancy. In Brazil, a revised version of the instrument (called the IFI-BR-27) was developed to use with fathers of children in a wider age group (2 to 10 years). Thus, in this study we aimed to investigate evidence for validity of this revised version based on internal structure, measurement invariance, and evidence of convergent validity. For this purpose, 572 Brazilian fathers completed a sociodemographic questionnaire, the IFI-BR-27, and either the Father Engagement Questionnaire (FEQ; for fathers of children in early childhood education settings) or the Inventory of Parenting Practices (IPP; for fathers of children in elementary school). Results of confirmatory factor analyses indicated the plausibility of a second-order internal structure for the IFI-BR-27 (χ 2 / df = 3.526; CFI = .937; TLI = .929; RMSEA = .066). Composite reliability for the nine factors varied from .65 to .84. Invariance analyses indicated that the structure is independent of the child's educational setting. Evidence of convergent validity was also found ( r = .67 - FEQ; r = .58 - IPP). Therefore, the IFI-BR-27 is an adequate tool to assess the quality of father involvement for fathers of children in preschool or elementary school. The IFI-BR-27 can contribute to further scientific research, aiding in longitudinal studies, as well as helping professionals to evaluate and encourage specific dimensions of father involvement.(AU)

O Inventory of Father Involvement (IFI) foi desenvolvido para avaliar o envolvimento paterno de homens com filhos de 5 a 10 anos. No entanto, envolvimento paterno afeta o desenvolvimento de crianças desde a primeira infância. No Brasil, uma versão revisada dessa medida (chamada de IFI-BR-27) foi desenvolvida para uso com pais de crianças em uma faixa etária mais ampla (2 a 10 anos). O objetivo deste estudo foi, portanto, investigar evidências de validade dessa versão revisada com base na estrutura interna, invariância de medida e evidências de validade convergente. Para isso, 572 pais brasileiros preencheram um questionário sociodemográfico, o IFI-BR-27 e o Questionário de Engajamento Paterno (QEP; para pais com filhos no Ensino Infantil) e o Inventário de Práticas Parentais (IPP; para pais com filhos no Ensino Fundamental 1). Os resultados de análises fatoriais confirmatórias indicaram a plausibilidade de uma estrutura interna de segunda ordem para o IFI-BR-27 (χ 2 / gl = 3,526; CFI = 0,937; TLI = 0,929; RMSEA = 0,066). A confiabilidade composta para os nove fatores variou de 0,65 a 0,84. Análises de invariância indicaram que a estrutura é independente do ciclo escolar da criança. Também foram encontradas evidências de validade convergente ( r = 0,67 - QEP; r = 0,58 - IPP). Assim, considera-se o IFI-BR-27 uma medida adequada para avaliar a qualidade do envolvimento paterno de pais de crianças do Ensino Infantil ao Fundamental 1. O IFI-BR-27 poderá contribuir para melhorias científicas, viabilizando estudos longitudinais e ajudando profissionais a avaliar e promover dimensões específicas do envolvimento paterno.(AU)

El Inventory of Father Involvement (IFI) se desarrolló para evaluar la participación paterna en la crianza de hijos de entre 5 y 10 años de edad. Es sabido que la participación paterna contribuye al desarrollo infantil desde la primera infancia. En Brasil, una versión brasileña de este instrumento (la IFI-BR-27) se desarrolló para aplicarse a padres con hijos de un grupo de edad más amplio (de 2 a 10 años). Este estudio tuvo por objetivo comprobar evidencia de validez de esta versión revisada con base en la estructura interna, la invariancia del instrumento y la evidencia de validez convergente. Para ello, 572 padres brasileños completaron un cuestionario sociodemográfico, el IFI-BR-27 y el Cuestionario de Involucramiento Paterno (CIP; para padres de niños en el jardín de infantes) y el Inventario de Prácticas Parentales (IPP; para padres de niños en la primaria). Los resultados de los análisis factoriales confirmatorios indicaron la plausibilidad de una estructura interna de segundo orden para el IFI-BR-27 (χ 2 / gl = 3,526; CFI = 0,937; TLI = 0,929; RMSEA =0,066). La confiabilidad compuesta para los nueve factores varió de 0,65 a 0,84. Los análisis de invariancia indicaron que la estructura es independiente del ciclo educativo del niño. También se encontró evidencia de validez convergente ( r =0,67 - CIP; r = 0,58 - IPP). Por lo tanto, el IFI-BR-27 es un instrumento adecuado para evaluar la calidad de participación paterna de padres con hijos en edad preescolar o en la primaria. El IFI-BR-27 permitirá un mayor desarrollo científico, permitiendo estudios longitudinales y ayudando a los profesionales a evaluar y fomentar dimensiones específicas de participación paterna.(AU)

Paternal effects on fetal programming

Paternal programming is the concept that the environmental signals from the sire's experiences leading up to mating can alter semen and ultimately affect the phenotype of resulting offspring. Potential mechanisms carrying the paternal effects to offspring can be associated with epigenetic signatures (DNA methylation, histone modification and non-coding RNAs), oxidative stress, cytokines, and the seminal microbiome. Several opportunities exist for sperm/semen to be influenced during development; these opportunities are within the testicle, the epididymis, or accessory sex glands. Epigenetic signatures of sperm can be impacted during the pre-natal and pre-pubertal periods, during sexual maturity and with advancing sire age. Sperm are susceptible to alterations as dictated by their developmental stage at the time of the perturbation, and sperm and seminal plasma likely have both dependent and independent effects on offspring. Research using rodent models has revealed that many factors including over/under nutrition, dietary fat, protein, and ingredient composition (e.g., macro- or micronutrients), stress, exercise, and exposure to drugs, alcohol, and endocrine disruptors all elicit paternal programming responses that are evident in offspring phenotype. Research using livestock species has also revealed that sire age, fertility level, plane of nutrition, and heat stress can induce alterations in the epigenetic, oxidative stress, cytokine, and microbiome profiles of sperm and/or seminal plasma. In addition, recent findings in pigs, sheep, and cattle have indicated programming effects in blastocysts post-fertilization with some continuing into post-natal life of the offspring. Our research group is focused on understanding the effects of common management scenarios of plane of nutrition and growth rates in bulls and rams on mechanisms resulting in paternal programming and subsequent offspring outcomes. Understanding the implication of paternal programming is imperative as short-term feeding and management decisions have the potential to impact productivity and profitability of our herds for generations to come.(AU)

Paternal effect does not affect in vitro embryo morphokinetics but modulates molecular profile.

The use of different sires influences in vitro embryo production (IVP) outcome. Paternal effects are observed from the first cleavages until after embryonic genome activation (EGA). Little is known about the mechanisms that promote in vitro fertility differences, even less about the consequences on embryo development. Therefore, this study aimed to evaluate the paternal effect at fertilization, embryo developmental kinetics, gene expression and quality from high and low in vitro fertility bulls. A retrospective analysis for bull selection was performed using the In vitro Brazil company database from 2012 to 2015. The dataset was edited employing cleavage and blastocyst rates ranking a total of 140 bulls. Subsequently, the dataset was restricted by embryo development rate (blastocyst/cleaved rate) and ten bulls were selected as high (HF; n = 5) and low (LF; n = 5) in vitro fertility groups. IVP embryos derived from high and low fertility bulls were classified according to their stage of development (2 cells, 3-4 cells, 6 cells, 8-16 cells), at 24, 36, 48, 60, 72 hpi, respectively, to evaluate embryo kinetics. Pronuclei formation (24 hpi), cleavage rate (Day 3), development rate, and blastocyst morphology (Grade I and II - Day 7) were also assessed, as well as the abundance of 96 transcripts at 8-16 cell stage and blastocysts. There was no difference in early embryo kinetics (P > 0.05), and cleavage rate (HF = 86.7%; LF = 84.9%; P = 0.25). Nevertheless, the fertilization rate was higher on HF (72%) than LF (62%) and the polyspermy rate was lower on HF compared to LF (HF:16.2% LF:29.2%). As expected, blastocyst rate (HF = 29.4%; LF = 16.0%; P < 0.0001) and development rate (HF = 33.9% LF = 18.9%; P < 0.0001) were higher in HF than LF. At the 8-16 cell stage, 22 transcripts were differentially represented (P ≤ 0.05) between the two groups. Only PGK1 and TFAM levels were higher in HF while transcripts related to stress (6/22, ∼27%), cell proliferation (6/22, ∼27%), lipid metabolism genes (5/22, ∼23%), and other cellular functions (5/22, ∼23%) were higher on LF embryos. Blastocysts had 9 differentially represented transcripts (P ≤ 0.05); being only ACSL3 and ELOV1 higher in the HF group. Lipid metabolism genes (3/9, 33%) and other cellular functions (6/9, 67%) were higher in the LF group. In conclusion, the timing of the first cleavages is not affected by in vitro bull fertility. However, low in vitro fertility bulls presented higher polyspermy rates and produced 8-16 cells embryos with higher levels of transcripts related to apoptosis and cell damage pathways compared to high in vitro fertility ones. Evidence such as polyspermy and increase in apoptotic and oxidative stress genes at the EGA stage suggest that embryo development is impaired in the LF group leading to the reduction of blastocyst rate.

Offspring from trained male mice inherit improved muscle mitochondrial function through PPAR co-repressor modulation.

Aim Investigate whether inheritance of improved skeletal muscle mitochondrial function and its association with glycemic control are multigenerational benefits of exercise. MAIN METHODS: Male Swiss mice were subjected to 8 weeks of endurance training and mated with untrained females. KEY FINDINGS: Trained fathers displayed typical endurance training-induced adaptations. Remarkably, offspring from trained fathers also exhibited higher endurance performance, mitochondrial oxygen consumption, glucose tolerance and insulin sensitivity. However, PGC-1α expression was not increased in the offspring. In the offspring, the expression of the co-repressor NCoR1 was reduced, increasing activation of PGC-1α target genes. These effects correlated with higher DNA methylation at the NCoR1 promoter in both, the sperm of trained fathers and in the skeletal muscle of their offspring. SIGNIFICANCE: Higher skeletal muscle mitochondrial function is inherited by epigenetic de-activation of a key PGC-1α co-repressor.

Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline.

BACKGROUND/AIMS: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease's (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. METHODS: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. RESULTS: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. CONCLUSION: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally.

"Distribution of paternal lineages in Mestizo populations throughout Mexico: an in silico study based on Y-STR haplotypes".

The Mexican-Mestizo population arose following European contact with the Americas due to the admixture of principally Spaniards, Native Americans, and Africans around 500 years ago. Because the paternal lineage distribution of the Mexican population has been poorly investigated, this study inferred the haplogroups of ten populations based on 1859 haplotypes (Y-STR data) using two haplogroup predictor programs. In the Mexican population sample, we found predominantly European ancestry (50.1%), followed by Native American (32.5%), Eurasian (13.4%), African (2.1%), East African-South Eurasian (1.3%), and Asian (0.6%) ancestries. In general, our results support a contrary north-to-south gradient throughout the Mexican territory of European and Native-American ancestries, respectively. Moreover, the presence of West-European R1b and Sub-Saharan African E1b1a haplogroups agrees with historical and genetic data of gene flow during the European conquest. This study represents the effort to analyze these paternal lineages on a large scale by taking advantage of Y-STR haplotype data to determine the distribution and ancestry proportions in this country.

The "maternal effect" on epilepsy risk: Analysis of familial epilepsies and reassessment of prior evidence.

OBJECTIVE: Previous studies have observed that epilepsy risk is higher among offspring of affected women than offspring of affected men. We tested whether this "maternal effect" was present in familial epilepsies, which are enriched for genetic factors that contribute to epilepsy risk. METHODS: We assessed evidence of a maternal effect in a cohort of families containing ≥3 persons with epilepsy using 3 methods: (1) "downward-looking" analysis, comparing the rate of epilepsy in offspring of affected women versus men; (2) "upward-looking" analysis, comparing the rate of epilepsy among mothers versus fathers of affected individuals; and (3) lineage analysis, comparing the proportion of affected individuals with family history of epilepsy on the maternal versus paternal side. RESULTS: Downward-looking analysis revealed no difference in epilepsy rates among offspring of affected mothers versus fathers (prevalence ratio = 1.0, 95% confidence interval [CI] = 0.8-1.2). Upward-looking analysis revealed more affected mothers than affected fathers; this effect was similar for affected and unaffected sibships (odds ratio = 0.8, 95% CI = 0.5-1.2) and was explained by a combination of differential fertility and participation rates. Lineage analysis revealed no significant difference in the likelihood of maternal versus paternal family history of epilepsy. INTERPRETATION: We found no evidence of a maternal effect on epilepsy risk in this familial epilepsy cohort. Confounding sex imbalances can create the appearance of a maternal effect in upward-looking analyses and may have impacted prior studies. We discuss possible explanations for the lack of evidence, in familial epilepsies, of the maternal effect observed in population-based studies. ANN NEUROL 2020;87:132-138.

Imprinting sets the stage for speciation.

Sexual imprinting-a phenomenon in which offspring learn parental traits and later use them as a model for their own mate preferences-can generate reproductive barriers between species1. When the target of imprinting is a mating trait that differs among young lineages, imprinted preferences may contribute to behavioural isolation and facilitate speciation1,2. However, in most models of speciation by sexual selection, divergent natural selection is also required; the latter acts to generate and maintain variation in the sexually selected trait or traits, and in the mating preferences that act upon them3. Here we demonstrate that imprinting, in addition to mediating female mate preferences, can shape biases in male-male aggression. These biases can act similarly to natural selection to maintain variation in traits and mate preferences, which facilitates reproductive isolation driven entirely by sexual selection. Using a cross-fostering study, we show that both male and female strawberry poison frogs (Oophaga pumilio) imprint on coloration, which is a mating trait that has diverged recently and rapidly in this species4. Cross-fostered females prefer to court mates of the same colour as their foster mother, and cross-fostered males are more aggressive towards rivals that share the colour of their foster mother. We also use a simple population-genetics model to demonstrate that when both male aggression biases and female mate preferences are formed through parental imprinting, sexual selection alone can (1) stabilize a sympatric polymorphism and (2) strengthen the trait-preference association that leads to behavioural reproductive isolation. Our study provides evidence of imprinting in an amphibian and suggests that this rarely considered combination of rival and sexual imprinting can reduce gene flow between individuals that bear divergent mating traits, which sets the stage for speciation by sexual selection.

Paternal heritage in Jujuy province (Northwest Argentina): Evidence for sex-biased gene flow and genetic drift effects.

OBJECTIVES: This study aimed to explore the diversity of paternal lineages in Jujuy province (Argentina) by analyzing Y chromosome markers. Furthermore, we examined among-population genetic variability based both on paternally (NRY haplotypes) and maternally (mtDNA haplogroups) inherited markers. We sought to evaluate the impact of sex-biased gene flow on genetic background in Jujuy, and contribute data on the microevolutionary forces acting in this zone. METHODS: DNA from 149 males from five Jujuy regions were analyzed for 12 non-recombining Y (NRY) markers. Genetic heterogeneity among Jujuy regions was evaluated through population differentiation tests. To identify potential genetic boundaries in Jujuy, analysis of molecular variance (AMOVA) and the Monmonier's algorithm implemented in the Barrier v2.2 software were employed. RESULTS: A clear divergence between Jujuy highlands and lowlands for NRY haplotypes was found. A marked discrepancy between genetic structuring for paternal lineages and the lack of geographical pattern for mitogenomes was confirmed by all statistical analyses. CONCLUSIONS: Genetic structuring of paternal lineages is most likely caused by admixture processes that have occurred since colonial times in the Jujuy lowlands. Immigrants were predominantly male that settled in the lower altitude zones, due to the steep orography of the region. Input of allochthonous male lineages because of gene flow toward the lowlands would have increased diversity of NRY markers, thus compensating for drift effects. Likewise, limited input of allochthonous mitogenomes would have promoted genetic drift, a key factor in the shaping of diversity of maternal lineages across Jujuy subpopulations, irrespective of altitude.

Diagnosis of Atelosteogenesis Type I suggested by Fetal Ultrasonography and Atypical Paternal Phenotype with Mosaicism.

Atelosteogenesis type I (AOI) is an autosomal dominant skeletal dysplasia caused by mutations in the filaminB (FLNB) gene with classic and well-recognizable clinical findings. However, parents affected with a mild phenotype, probably with somatic mosaicism, can generate offspring with a much more severe phenotype of AOI. In the present report, we describe a female newborn with classic AOI leading to early neonatal death, whose diagnostic was based on prenatal radiological findings and on the physical examination of the father. Since her father had limb deformities and corporal asymmetry, suggesting somatic mosaicism, his biological samples were analyzed through a gene panel for skeletal dysplasias. A missense mutation not previously described in the literature was detected in the FLNB gene, affecting ∼ 20% of the evaluated cells and, therefore, confirming the diagnosis of mosaic AOI in the father. The molecular analysis of the father was crucial to suggest the diagnosis of AOI in the newborn, since she died early and there were no biological samples available.

A atelosteogênese tipo I (AOI) é uma displasia esquelética autossômica dominante causada por mutações no gene filamina B (FLNB) com achados clínicos clássicos e bem reconhecíveis. No entanto, pais afetados com um fenótipo mais leve, provavelmente com mosaicismo somático, podem gerar uma prole com um fenótipo muito mais grave de AOI. No presente relato, descrevemos um recém-nascido do sexo feminino com AOI clássica, que levou à morte neonatal precoce, e cujo diagnóstico foi baseado em achados radiológicos pré-natais e no exame físico de seu genitor. Como o genitor apresentava deformidades em membros e assimetria corporal, que sugeriam mosaicismo somático, suas amostras biológicas foram analisadas por meio de um painel de genes para displasias esqueléticas. Uma mutação missense, não descrita anteriormente na literatura, foi detectada no gene FLNB, afetando ∼ 20% das células avaliadas, e, portanto, confirmando o diagnóstico de AOI em mosaico no genitor. A análise molecular realizada no genitor foi fundamental para sugerir o diagnóstico de AOI na recém-nascida, uma vez que esta morreu precocemente, e não havia amostras biológicas disponíveis.

Diagnosis of atelosteogenesis type I suggested by fetal ultrasonography and atypical paternal phenotype with mosaicism / Diagnóstico de atelosteogênese tipo I sugerido por ultrassonografia fetal e fenótipo paterno atípico com mosaicismo

Abstract Atelosteogenesis type I (AOI) is an autosomal dominant skeletal dysplasia caused by mutations in the filamin B (FLNB) gene with classic and well-recognizable clinical findings. However, parents affected with a mild phenotype, probably with somatic mosaicism, can generate offspring with a much more severe phenotype of AOI. In the present report, we describe a female newborn with classic AOI leading to early neonatal death, whose diagnostic was based on prenatal radiological findings and on the physical examination of the father. Since her father had limb deformities and corporal asymmetry, suggesting somatic mosaicism, his biological samples were analyzed through a gene panel for skeletal dysplasias. A missense mutation not previously described in the literature was detected in the FLNB gene, affecting ~ 20% of the evaluated cells and, therefore, confirming the diagnosis ofmosaic AOI in the father. The molecular analysis of the father was crucial to suggest the diagnosis of AOI in the newborn, since she died early and there were no biological samples available.

Resumo A atelosteogênese tipo I (AOI) é uma displasia esquelética autossômica dominante causada por mutações no gene filamina B (FLNB) comachados clínicos clássicos e bem reconhecíveis. No entanto, pais afetados com um fenótipo mais leve, provavelmente commosaicismo somático, podem gerar uma prole comumfenótipomuito mais grave de AOI. No presente relato, descrevemos um recém-nascido do sexo feminino comAOI clássica, que levou à morte neonatal precoce, e cujo diagnóstico foi baseado em achados radiológicos pré-natais e no exame físico de seu genitor. Como o genitor apresentava deformidades em membros e assimetria corporal, que sugeriam mosaicismo somático, suas amostras biológicas foram analisadas por meio de um painel de genes para displasias esqueléticas. Umamutação missense, não descrita anteriormente na literatura, foi detectada no gene FLNB, afetando ~ 20% das células avaliadas, e, portanto, confirmando o diagnóstico de AOI em mosaico no genitor. A análise molecular realizada no genitor foi fundamental para sugerir o diagnóstico de AOI na recém-nascida, uma vez que esta morreu precocemente, e não havia amostras biológicas disponíveis.

Biological compatibility between two temperate lineages of brown dog ticks, Rhipicephalus sanguineus (sensu lato).

BACKGROUND: The brown dog tick Rhipicephalus sanguineus (sensu stricto) is reputed to be the most widespread tick of domestic dogs worldwide and has also been implicated in the transmission of many pathogens to dogs and humans. For more than two centuries, Rh. sanguineus (s.s.) was regarded as a single taxon, even considering its poor original description and the inexistence of a type specimen. However, genetic and crossbreeding experiments have indicated the existence of at least two distinct taxa within this name: the so-called "temperate" and "tropical" lineages of Rh. sanguineus (sensu lato). Recent genetic studies have also demonstrated the existence of additional lineages of Rh. sanguineus (s.l.) in Europe and Asia. Herein, we assessed the biological compatibility between two lineages of Rh. sanguineus (s.l.) found in southern Europe, namely Rhipicephalus sp. I (from Italy) and Rhipicephalus sp. II (from Portugal). METHODS: Ticks morphologically identified as Rh. sanguineus (s.l.) were collected in southern Portugal and southern Italy. Tick colonies were established and crossbreeding experiments conducted. Morphological, biological and genetic analyses were conducted. RESULTS: Crossbreeding experiments confirmed that ticks from the two studied lineages were able to mate and generate fertile hybrids. Hybrid adult ticks always presented the same genotype of the mother, confirming maternal inheritance of mtDNA. However, larvae and nymphs originated from Rhipicephalus sp. I females presented mtDNA genotype of either Rhipicephalus sp. I or Rhipicephalus sp. II, suggesting the occurrence of paternal inheritance or mitochondrial heteroplasmy. While biologically compatible, these lineages are distinct genetically and phenotypically. CONCLUSIONS: The temperate lineages of Rh. sanguineus (s.l.) studied herein are biologically compatible and genetic data obtained from both pure and hybrid lines indicate the occurrence of paternal inheritance or mitochondrial heteroplasmy. This study opens new research avenues and raises question regarding the usefulness of genetic data and crossbreeding experiments as criteria for the definition of cryptic species in ticks.

Genetic variation in populations from central Argentina based on mitochondrial and Y chromosome DNA evidence.

We present new data and analysis on the genetic variation of contemporary inhabitants of central Argentina, including a total of 812 unrelated individuals from 20 populations. Our goal was to bring new elements for understanding micro-evolutionary and historical processes that generated the genetic diversity of the region, using molecular markers of uniparental inheritance (mitochondrial DNA and Y chromosome). Almost 76% of the individuals show mitochondrial lineages of American origin. The Native American haplogroups predominate in all surveyed localities, except in one. The larger presence of Eurasian maternal lineages were observed in the plains (Pampas) of the southeast, whereas the African lineages are more frequent in northern Córdoba. On the other hand, the analysis of 258 male samples reveals that 92% of them present Eurasian paternal lineages, 7% carry Native American haplogroups, and only 1% of the males show African lineages. The maternal lineages have high genetic diversity homogeneously distributed throughout central Argentina, probably as result of a recent common origin and sustained gene flow. Migratory events that occurred in colonial and recent times should have contributed to hiding any traces of differentiation that might have existed in the past. The analysis of paternal lineages showed also homogeneous distribution of the variation together with a drastic reduction of the native male population.

Developmental Origins of Breast Cancer: A Paternal Perspective.

The developmental origins of breast cancer have been considered predominantly from a maternal perspective. Although accumulating evidence suggests a paternal programming effect on metabolic diseases, the potential impact of fathers' experiences on their daughters' breast cancer risk has received less attention. In this chapter, we focus on the developmental origins of breast cancer and examine the emerging evidence for a role of fathers' experiences.

Investigation of Paternal Programming of Breast Cancer Risk in Female Offspring in Rodent Models.

Emerging experimental evidence show that fathers' experiences during preconception can influence their daughters' risk of developing breast cancer. Here we describe detailed protocols for investigation in rats and mice of paternally mediated breast cancer risk programming effects.

Paternally Inherited DLK1 Deletion Associated With Familial Central Precocious Puberty.

Context: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis. Few genetic causes of CPP have been identified, with the most common being mutations in the paternally expressed imprinted gene MKRN3. Objective: To identify the genetic etiology of CPP in a large multigenerational family. Design: Linkage analysis followed by whole-genome sequencing was performed in a family with five female members with nonsyndromic CPP. Detailed phenotyping was performed at the time of initial diagnosis and long-term follow-up, and circulating levels of Delta-like 1 homolog (DLK1) were measured in affected individuals. Expression of DLK1 was measured in mouse hypothalamus and in kisspeptin-secreting neuronal cell lines in vitro. Setting: Endocrine clinic of an academic medical center. Patients: Patients with familial CPP were studied. Results: A complex defect of DLK1 (∼14-kb deletion and 269-bp duplication) was identified in this family. This deletion included the 5' untranslated region and the first exon of DLK1, including the translational start site. Only family members who inherited the defect from their father have precocious puberty, consistent with the known imprinting of DLK1. The patients did not demonstrate additional features of the imprinted disorder Temple syndrome except for increased fat mass. Serum DLK1 levels were undetectable in all affected individuals. Dlk1 was expressed in mouse hypothalamus and in kisspeptin neuron-derived cell lines. Conclusion: We identified a genomic defect in DLK1 associated with isolated familial CPP. MKRN3 and DLK1 are both paternally expressed imprinted genes. These findings suggest a role of genomic imprinting in regulating the timing of human puberty.

Inferring paternal history of rural African-derived Brazilian populations from Y chromosomes.

OBJECTIVES: Quilombo remnants are relics of communities founded by runaway or abandoned African slaves, but often with subsequent extensive and complex admixture patterns with European and Native Americans. We combine a genetic study of Y-chromosome markers with anthropological surveys in order to obtain a portrait of quilombo structure and history in the region that has the largest number of quilombo remnants in the state of São Paulo. METHODS: Samples from 289 individuals from quilombo remnants were genotyped using a set of 17 microsatellites on the Y chromosome (AmpFlSTR-Yfiler). A subset of 82 samples was also genotyped using SNPs array (Axiom Human Origins-Affymetrix). We estimated haplotype and haplogroup frequencies, haplotype diversity and sharing, and pairwise genetic distances through FST and RST indexes. RESULTS: We identified 95 Y chromosome haplotypes, classified into 15 haplogroups. About 63% are European, 32% are African, and 6% Native American. The most common were: R1b (European, 34.2%), E1b1a (African, 32.3%), J1 (European, 6.9%), and Q (Native American, 6.2%). Genetic differentiation among communities was low (FST = 0.0171; RST = 0.0161), and haplotype sharing was extensive. Genetic, genealogical and oral surveys allowed us to detect five main founder haplotypes, which explained a total of 27.7% of the Y chromosome lineages. CONCLUSIONS: Our results showed a high European patrilineal genetic contribution among the founders of quilombos, high amounts of gene flow, and a recent common origin of these populations. Common haplotypes and genealogical data indicate the origin of quilombos from a few male individuals. Our study reinforces the importance of a dual approach, involving the analysis of both anthropological and genetic data.

Males with Paternally Inherited MKRN3 Mutations May Be Asymptomatic.

Ten girls with sporadic central precocious puberty were screened for mutations in the maternally imprinted gene MKRN3. We detected 1 novel frameshift mutation (p.Arg351Serfs*44) and a previously described mutation (p.Pro161Argfs*10). In the course of investigating the family, genetic analysis found 2 asymptomatic males with paternally inherited MKRN3 mutations, which has not been reported in previous studies.

Two girls with a de novo Xq rearrangement of paternal origin: t(X;9)(q24;q12) or rea(X)dup q.

OBJECTIVE: We report on two rare Xq rearrangements, namely a t(X;9)(q24;q12) found in a mildly-affected girl (Patient 1) and a rea(X)dup q concomitant with a rob(14;21)mat in a Down syndrome girl (Patient 2). CASE REPORT: Both rearrangements were characterized by banding techniques [Giemsa (G), constitutive heterochromatin (C), and bromodeoxyuridine (BrdU) pulse], fluorescence in situ hybridization (FISH) assays, human androgen receptor (HUMAR) assays, and microarray analyses. Patient 1 had a t(X;9)(q24;q12)dn. Patient 2 had a de novo rea(X)(qter→q23 or q24::p11.2→qter) concomitant with an unbalanced rob(14;21)mat. X-Inactivation studies in metaphases and DNA revealed a fully skewed inactivation: the normal homolog was silenced in Patient 1 and the rea(X) in Patient 2. Both rearranged X chromosomes were of paternal descent. Microarray analyses revealed no imbalances in Patient 1 whereas loss of Xp (∼52 Mb) and duplication of Xq (∼44 Mb) and 21q were confirmed in Patient 2. CONCLUSION: Our observations further document the cytogenetic heterogeneity and predominant paternal origin of certain de novo X-chromosome rearrangements.