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1.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492

RESUMO

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidades
2.
Nat Commun ; 11(1): 5404, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106479

RESUMO

There is a robust observational relationship between lower birthweight and higher risk of cardiometabolic disease in later life. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that adverse environmental factors in utero increase future risk of cardiometabolic disease. Here, we explore if a genetic risk score (GRS) of maternal SNPs associated with offspring birthweight is also associated with offspring cardiometabolic risk factors, after controlling for offspring GRS, in up to 26,057 mother-offspring pairs (and 19,792 father-offspring pairs) from the Nord-Trøndelag Health (HUNT) Study. We find little evidence for a maternal (or paternal) genetic effect of birthweight associated variants on offspring cardiometabolic risk factors after adjusting for offspring GRS. In contrast, offspring GRS is strongly related to many cardiometabolic risk factors, even after conditioning on maternal GRS. Our results suggest that the maternal intrauterine environment, as proxied by maternal SNPs that influence offspring birthweight, is unlikely to be a major determinant of adverse cardiometabolic outcomes in population based samples of individuals.


Assuntos
Peso ao Nascer , Doenças Cardiovasculares/genética , Herança Materna , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Análise da Randomização Mendeliana , Noruega/epidemiologia , Herança Paterna , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto Jovem
3.
Nat Commun ; 11(1): 5417, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110091

RESUMO

De novo DNA methylation (DNAme) during mammalian spermatogenesis yields a densely methylated genome, with the exception of CpG islands (CGIs), which are hypomethylated in sperm. While the paternal genome undergoes widespread DNAme loss before the first S-phase following fertilization, recent mass spectrometry analysis revealed that the zygotic paternal genome is paradoxically also subject to a low level of de novo DNAme. However, the loci involved, and impact on transcription were not addressed. Here, we employ allele-specific analysis of whole-genome bisulphite sequencing data and show that a number of genomic regions, including several dozen CGI promoters, are de novo methylated on the paternal genome by the 2-cell stage. A subset of these promoters maintains DNAme through development to the blastocyst stage. Consistent with paternal DNAme acquisition, many of these loci are hypermethylated in androgenetic blastocysts but hypomethylated in parthenogenetic blastocysts. Paternal DNAme acquisition is lost following maternal deletion of Dnmt3a, with a subset of promoters, which are normally transcribed from the paternal allele in blastocysts, being prematurely transcribed at the 4-cell stage in maternal Dnmt3a knockout embryos. These observations uncover a role for maternal DNMT3A activity in post-fertilization epigenetic reprogramming and transcriptional silencing of the paternal genome.


Assuntos
Blastocisto/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Genoma , Herança Materna , Herança Paterna , Alelos , Animais , Ilhas de CpG , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , Epigenômica , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Camundongos Endogâmicos DBA , Oócitos/metabolismo , Espermatozoides/metabolismo
4.
Bull Entomol Res ; 110(6): 694-699, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32912368

RESUMO

Body size is a trait with many potential impacts on fitness. Adult body size can affect the strength of condition-dependent parental effects that determine offspring phenotypes, with potentially important transgenerational consequences. In a preliminary experiment, larval food deprivation (30 min daily access) created Harmonia axyridis Pallas (Coleoptera: Coccinellidae) females that weighed <50% of controls reared on ad libitum food (eggs of Ephestia kuehniella Zeller). Although only 1/3 of larvae survived to adulthood in the 30 min treatment, adult pairs produced eggs that were not significantly different in size from those of pairs fed ad libitum as larvae. Less extreme larval food deprivation (4 h daily access) was used to create a cohort of H. axyridis that weighed <60% of controls reared on ad libitum food. Small couples had lower 20-day fecundities and reduced egg fertility relative to large couples. Both egg and pupal periods were shortest when both parents were small, and longest when both parents were large, with reciprocal crosses intermediate. There were no consistent effects of parental body size on larval development time, but the progeny of small females mated to large males pupated later than other treatments. Progeny of large pairs had the heaviest adult weights at emergence, and progeny of small pairs, the lightest, with the progeny of reciprocal crosses intermediate. Small females produced the lightest female offspring, whereas small males sired the lightest male offspring, suggesting stronger responses to epigenetic signals from parents of the same sex. These results indicate that H. axyridis cohorts maturing with abundant food will produce progeny with larger potential body size and fitness, whereas those experiencing food limitation will confer size and fitness limitations to the subsequent generation, with potentially important implications for short-term population dynamics.


Assuntos
Tamanho Corporal , Besouros/crescimento & desenvolvimento , Besouros/fisiologia , Privação de Alimentos , Animais , Feminino , Fertilidade , Larva/crescimento & desenvolvimento , Larva/fisiologia , Masculino , Herança Materna , Mariposas , Óvulo , Herança Paterna , Fenótipo , Reprodução/fisiologia
5.
Leg Med (Tokyo) ; 47: 101760, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32739877

RESUMO

24 Y-STR loci were analyzed in 223 Altay Hui individuals and 209 Altay Kazakh individuals. Haplotype diversity (HD) and discrimination capacity (DC) values were calculated. Population pairwise genetic distances (Rst) were evaluated in AMOVA analysis and compared between two studied populations and other populations. The relationships between populations were visualized through multidimensional scaling (MDS) and neighbor-joining (NJ) tree. The results indicated higher discrimination power in the Altay Kazakh and Hui populations. The Altay Kazakh was the most distantly related to Xishuangbanna Dai, while Altay Kazakh was the most closely related to Gansu Kazakh. The results may provide useful information for paternal lineages and increase our understanding of genetic relationships between two studied populations and other populations.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Cromossomos Humanos Y/genética , Grupos Étnicos/genética , Loci Gênicos/genética , Variação Genética/genética , Genética Populacional , Repetições de Microssatélites/genética , Polimorfismo Genético , China/etnologia , Feminino , Haplótipos , Humanos , Masculino , Herança Paterna/genética
6.
Ann Hum Biol ; 47(3): 294-299, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32281408

RESUMO

Background: Due to their long history, complex admixture processes and large population sizes, more research is required to explore the fine genetic structure of Han populations from different geographic locations of China.Aim: To characterise the paternal genetic structure of the Han Chinese in Henan province, which was once the central living region of the ancient Huaxia population, the precursors of the Han Chinese.Subjects and methods: We sequenced Y chromosomes of 60 males from Zhengzhou, Henan Province, and reconstructed a phylogenetic tree for these samples with age estimation.Results: We observed high diversity of paternal lineages in our collection. We found that the in situ Neolithic expansion of the "Major lineages" contributed to a large portion of the paternal gene pool of the Han population in Henan Province. We also detected a large number of "Minor lineages" that diverged in the Palaeolithic Age.Conclusion: We suggest that the high genetic diversity in the paternal gene pool of modern Han populations is mainly attributed to the reservation of a larger number of lineages that diverged in the Palaeolithic Age, while the recent expansion of limited lineages contributed to the majority of the gene pool of modern Han populations. We propose that such a structure is a basal characteristic for the genetic structure of modern Han populations.


Assuntos
Cromossomos Humanos Y/genética , Frequência do Gene , Variação Genética , Herança Paterna , China , Humanos , Masculino
7.
Urol Clin North Am ; 47(2): 219-225, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272994

RESUMO

Transgenerational epigenetic inheritance provides a mechanism by which environmental exposures and lifestyle decisions can affect the offspring directly through the gamete. It is this pattern of inheritance that has shed light on the fact that preconception lifestyle decisions that a father makes are significant because they can significantly impact the offspring. Understanding the epigenetic alterations in gametes and the potential implications of these changes is key to the health of future generations.


Assuntos
Epigênese Genética/genética , Infertilidade Masculina/genética , Exposição Paterna , Herança Paterna/genética , Espermatogênese/genética , Efeito de Coortes , Metilação de DNA/genética , Humanos , Infertilidade Masculina/etiologia , Masculino , Exposição Paterna/efeitos adversos
8.
Urol Clin North Am ; 47(2): 257-270, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272997

RESUMO

The male contribution to infertility has traditionally been overlooked, or at best oversimplified. In recent years efforts have been made to optimize diagnostic and therapeutic techniques to maximize fertility outcomes. A renewed focus on the male partner has resulted in an increased understanding of both genetic and epigenetic changes within the male germline. Furthermore, single-nucleotide polymorphisms, copy-number variants, DNA damage, sperm cryopreservation, obesity, and paternal age have recently been recognized as important factors that play a role in male fertility. Developing a deeper knowledge of these issues could potentially lead to improved success with assisted reproductive technology.


Assuntos
Epigênese Genética/genética , Fertilização In Vitro/tendências , Infertilidade Masculina/genética , Infertilidade Masculina/terapia , Obesidade/genética , Herança Paterna/genética , Fatores Etários , Criopreservação , Dano ao DNA/genética , Feminino , Fertilização In Vitro/efeitos adversos , Fertilização In Vitro/métodos , Previsões , Humanos , Infertilidade Masculina/etiologia , Masculino , Mutação , Obesidade/complicações , Polimorfismo Genético/genética , Técnicas de Reprodução Assistida/efeitos adversos , Técnicas de Reprodução Assistida/tendências
9.
Nat Commun ; 11(1): 1740, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269217

RESUMO

Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans.


Assuntos
Núcleo Celular/genética , DNA Mitocondrial/genética , Herança Paterna/genética , Família , Feminino , Haplótipos/genética , Humanos , Masculino , Modelos Genéticos , Linhagem , Reprodutibilidade dos Testes
10.
Genet Epidemiol ; 44(4): 395-399, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220115

RESUMO

We present an important characteristic of trio models which may lead to bias and loss of power when one parent is unmodeled in trio analyses. Motivated by recent interest in estimating parental effects on postnatal and later-life phenotypes, we consider a causal model where each parent has both an effect on their child's phenotype which is mediated through the genotype transmitted to the child and a direct effect on the phenotype through the parentally provided environment. We derive the power and bias of models in which one parent's genotype is not modeled, showing that while the effect of the child's genotype is biased in the direction of the unmodeled parent's effect as expected, the estimated effect of the observed parent's genotype is also biased in the opposite direction. While this phenomenon may not be intuitive under the assumption of random mating, it can be explained by intermediate confounding of the child's genotype-phenotype effect. These observations have implications for the accurate estimation of maternal and paternal effects in trio data sets with missing genotype data.


Assuntos
Modelos Genéticos , Criança , Feminino , Genótipo , Humanos , Masculino , Herança Materna/genética , Herança Paterna/genética , Fenótipo
11.
Evol Anthropol ; 29(4): 180-200, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32196832

RESUMO

Recently, novel experimental approaches and molecular techniques have demonstrated that a male's experiences can be transmitted through his germline via epigenetic processes. These findings suggest that paternal exposures influence phenotypic variation in unexposed progeny-a proposal that runs counter to canonical ideas about inheritance developed during the 20th century. Nevertheless, support for paternal germline epigenetic inheritance (GEI) in nonhuman mammals continues to grow and the mechanisms underlying this phenomenon are becoming clearer. To what extent do similar processes operate in humans, and if so, what are their implications for understanding human phenotypic variation, health, and evolution? Here, we review evidence for GEI in human and nonhuman mammals and evaluate these findings in relation to historical conceptions of heredity. Drawing on epidemiological data, reproductive biology, and molecular embryology, we outline developments and opportunities for the study of GEI in human populations, emphasizing the challenges that researchers in this area still face.


Assuntos
Epigênese Genética , Células Germinativas/fisiologia , Hereditariedade , Mamíferos/genética , Herança Paterna , Animais , Pai , Humanos
12.
Biol Lett ; 16(2): 20190945, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32097600

RESUMO

Studies often show that paternal age affects offspring fitness. However, such effects could be due either to age, or to a male's previous mating effort (which is necessarily confounded with age). We experimentally tested whether differences in the mating history of old males affect offspring performance in the mosquitofish Gambusia holbrooki. Upon maturation, males were housed for a duration of the natural field-breeding season (23 weeks) either with mating access to females (lifetime-mating), or with visual but no physical access to females (no-mating). We then paired these males with a female to test whether male mating history had a significant effect on their mate's breeding success or offspring performance. The daughters, but not the sons, of 'no-mating' treatment males matured significantly sooner, and at a significantly smaller size, than those of 'lifetime-mating' treatment males. There was, however, no effect of male mating history on their daughters' initial fecundity, or on proxy measures of their sons' reproductive success. These results, when combined with earlier studies showing effects of male mating history on sperm quality, growth and immunity, suggest that variation in paternal effects currently attributed to male age could partly arise because older males have usually mated more often than younger males.


Assuntos
Ciprinodontiformes , Comportamento Sexual Animal , Animais , Feminino , Fertilidade , Masculino , Herança Paterna , Reprodução
13.
BMC Vet Res ; 16(1): 33, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005239

RESUMO

BACKGROUND: In dairy herds, mastitis causes detrimental economic losses. Genetic selection offers a sustainable tool to select animals with reduced susceptibility towards postpartum diseases. Studying underlying mechanisms is important to assess the physiological processes that cause differences between selected haplotypes. Therefore, the objective of this study was to establish an in vivo infection model to study the impact of selecting for alternative paternal haplotypes in a particular genomic region on cattle chromosome 18 for mastitis susceptibility under defined conditions in uniparous dairy cows. RESULTS: At the start of pathogen challenge, no significant differences between the favorable (Q) and unfavorable (q) haplotypes were detected. Intramammary infection (IMI) with Staphylococcus aureus 1027 (S. aureus, n = 24, 96 h) or Escherichia coli 1303 (E. coli, n = 12, 24 h) was successfully induced in all uniparous cows. This finding was confirmed by clinical signs of mastitis and repeated recovery of the respective pathogen from milk samples of challenged quarters in each animal. After S. aureus challenge, Q-uniparous cows showed lower somatic cell counts 24 h and 36 h after challenge (P < 0.05), lower bacterial shedding in milk 12 h after challenge (P < 0.01) and a minor decrease in total milk yield 12 h and 24 h after challenge (P < 0.01) compared to q-uniparous cows. CONCLUSION: An in vivo infection model to study the impact of genetic selection for mastitis susceptibility under defined conditions in uniparous dairy cows was successfully established and revealed significant differences between the two genetically selected haplotype groups. This result might explain their differences in susceptibility towards IMI. These clinical findings form the basis for further in-depth molecular analysis to clarify the underlying genetic mechanisms for mastitis resistance.


Assuntos
Mastite Bovina/genética , Mastite Bovina/microbiologia , Herança Paterna , Animais , Bovinos , Indústria de Laticínios , Escherichia coli , Infecções por Escherichia coli/veterinária , Feminino , Haplótipos , Masculino , Leite/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus
14.
Sci Rep ; 10(1): 3614, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32109236

RESUMO

In humans, parthenogenesis and androgenesis occur naturally in mature cystic ovarian teratomas and androgenetic complete hydatidiform moles (CHM), respectively. Our previous study has reported human parthenogenetic induced pluripotent stem cells from ovarian teratoma-derived fibroblasts and screening of imprinted genes using genome-wide DNA methylation analysis. However, due to the lack of the counterparts of uniparental cells, identification of new imprinted differentially methylated regions has been limited. CHM are inherited from only the paternal genome. In this study, we generated human androgenetic induced pluripotent stem cells (AgHiPSCs) from primary androgenetic fibroblasts derived from CHM. To investigate the pluripotency state of AgHiPSCs, we analyzed their cellular and molecular characteristics. We tested the DNA methylation status of imprinted genes using bisulfite sequencing and demonstrated the androgenetic identity of AgHiPSCs. AgHiPSCs might be an attractive alternative source of human androgenetic embryonic stem cells. Furthermore, AgHiPSCs can be used in regenerative medicine, for analysis of genomic imprinting, to study imprinting-related development, and for disease modeling in humans.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Herança Paterna , Diferenciação Celular , Células Cultivadas , Metilação de DNA , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Impressão Genômica , Humanos , Mola Hidatiforme/genética , Mola Hidatiforme/metabolismo , Mola Hidatiforme/fisiopatologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Gravidez , Reprodução Assexuada
15.
Mol Genet Genomics ; 295(3): 579-589, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31932897

RESUMO

We have determined the distribution of Y-chromosomal haplotypes and haplogroups in the Yong population, one of the largest and well-known ethnic groups that began migrating southward from China to Thailand centuries ago. Their unique mass migration pattern provided great opportunities for researchers to study the genetic links of the transboundary migration movements among the peoples of China, Myanmar and Thailand. We analysed relevant male-specific markers, such as Y-STRs and Y-SNPs, and the distribution of 23 Y-STRs of 111 Yong individuals and 116 nearby ethnic groups including the Shan, Northern Thai, Lawa, Lua, Skaw, Pwo and Padong groups. We found that the general haplogroup distribution values were similar among different populations; however, the haplogroups O1b-M268 and O2-M112 constituted the vast majority of these values. In contrast with previous maternal lineage studies, the paternal lineage of the Yong did not relate to the Xishuangbanna Dai people, who represent their historically documented ancestors. However, they did display a close genetic affinity to other prehistoric Tai-Kadai speaking groups in China such as the Zhuang and Bouyei. Low degrees of genetic admixture within the populations who belonged to the Austroasiatic and Sino-Tibetan linguistic families were observed in the gene pool of the Yong populations. Resettlement in northern Thailand in the early part of the nineteenth century AD, by way of mass migration trend, was able to preserve the Yong's ancestral genetic background in terms of the way they had previously lived in China and Myanmar. Our study has revealed similar genetic structures among ethnic populations in northern Thailand and southern China, and has identified and emphasized an ancient Tai-Kadai patrilineal ancestry line in the Yong ethnic group.


Assuntos
Cromossomos Humanos Y/genética , DNA Mitocondrial/genética , Grupos Étnicos/genética , Variação Genética , Genética Populacional , Haplótipos , Herança Paterna , Migração Humana , Humanos , Masculino , Tailândia
16.
Am J Phys Anthropol ; 171(3): 520-528, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31845317

RESUMO

OBJECTIVES: Telomeres, emerging biomarkers of aging, are comprised of DNA repeats located at chromosomal ends that shorten with cellular replication and age in most human tissues. In contrast, spermatocyte telomeres lengthen with age. These changes in telomere length (TL) appear to be heritable, as older paternal ages of conception (PAC) predict longer offspring TL. Mouse-model studies raise questions about the potential for effects of paternal experiences on human offspring TL, as they suggest that smoking, inflammation, DNA damage, and stressors all shorten sperm TL. Here, we examined whether factors from the paternal environment predict offspring TL as well as interact with PAC to predict offspring TL. MATERIALS AND METHODS: Using data from the Philippines, we tested if smoking, psychosocial stressors, or shorter knee height (a measure of early life adversity) predict shorter offspring TL. We also tested if these interacted with PAC in predicting offspring TL. RESULTS: While we did not find the predicted associations, we observed a trend toward fathers with shorter knee height having offspring with longer TL. In addition, we found that knee height interacted with PAC to predict offspring TL. Specifically, fathers with shorter knee heights showed a stronger positive effect of PAC on offspring TL. DISCUSSION: While the reasons for these associations remain uncertain, shorter knee height is characteristic of earlier puberty. Since spermatocyte TL increases with the production of sperm, we speculate that individuals with earlier puberty, and its concomitant commencement of production of sperm, had more time to accumulate longer sperm telomeres.


Assuntos
Estatura , Herança Paterna , Fumar/efeitos adversos , Estresse Psicológico/psicologia , Homeostase do Telômero/genética , Encurtamento do Telômero/genética , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Filipinas , Adulto Jovem
17.
Evolution ; 74(2): 404-418, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31883271

RESUMO

Parental experience alters survival-related phenotypes of offspring in both adaptive and nonadaptive ways, yielding rapid inter- and transgenerational fitness effects. Yet, fitness comprises survival and reproduction, and parental effects on mating decisions could alter the strength and direction of sexual selection, affecting long-term evolutionary trajectories. We used a full factorial design in which threespine stickleback (Gasterosteus aculeatus) mothers, fathers, both, or neither were exposed to a model predator at developmentally appropriate times to test for predator-induced maternal, paternal, and joint parental effects on daughters' mating behavior. We tested the responsiveness, preferences, and mate choices of adult daughters in no-choice trials with wild-caught males who had varied sexual signals. Maternal and paternal predator exposure independently yielded daughters who preferred males who were intermediate in conspicuousness (with duller nuptial coloration and who courted less vigorously), relaxing the typical preference for the most conspicuous males. The combined effects of maternal and paternal predator exposure were not cumulative; when both parents were predator exposed, single-parent effects on mate preferences were reversed. Thus, we cannot assume that maternal and paternal effects additively combine to produce "parental" effects. Further, joint parental predator exposure yielded daughters who were three times less likely to mate at all. Stress-induced intergenerational parental effects on reproductive decisions such as those observed here may potentiate rapid transgenerational responses to novel and changing mating environments.


Assuntos
Herança Materna , Preferência de Acasalamento Animal , Herança Paterna , Smegmamorpha/fisiologia , Animais , Feminino , Cadeia Alimentar , Masculino , Fenótipo , Smegmamorpha/genética
18.
Ann Neurol ; 87(1): 132-138, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31637767

RESUMO

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.


Assuntos
Síndromes Epilépticas/epidemiologia , Saúde da Família/estatística & dados numéricos , Herança Materna , Herança Paterna , Síndromes Epilépticas/genética , Feminino , Humanos , Masculino , Prevalência , Fatores Sexuais , Estados Unidos/epidemiologia
19.
J Clin Endocrinol Metab ; 105(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31544945

RESUMO

OBJECTIVE: IGF2 is a paternally expressed growth-promoting gene. Here, we report five cases with IGF2 mutations and review IGF2 mutation-positive patients described in the literature. We also compare clinical features between patients with IGF2 mutations and those with H19/IGF2:IG-DMR epimutations. RESULTS: We recruited five cases with IGF2 mutations: case 1 with a splice site mutation (c.-6-1G>C) leading to skipping of exon 2 and cases 2-5 with different missense mutations (p.(Cys70Tyr), p.(Cys71Arg), p.(Cys33Ser), and p.(Cys45Ser)) affecting cysteine residues involved in the S-S bindings. All the mutations resided on the paternally inherited allele, and the mutation of case 5 was present in a mosaic condition. Clinical assessment revealed Silver-Russell syndrome (SRS) phenotype with Netchine-Harbison scores of ≥5/6 in all the apparently nonmosaic 14 patients with IGF2 mutations (cases 1-4 described in this study and 10 patients reported in the literature). Furthermore, compared with H19/IGF2:IG-DMR epimutations, IGF2 mutations were associated with low frequency of hemihypoplasia, high frequency of feeding difficulty and/or reduced body mass index, and mild degree of relative macrocephaly, together with occasional development of severe limb malformations, high frequency of cardiovascular anomalies and developmental delay, and low serum IGF-II values. CONCLUSIONS: This study indicates that IGF2 mutations constitute a rare but important cause of SRS. Furthermore, while both IGF2 mutations and H19/IGF2:IG-DMR epimutations lead to SRS, a certain degree of phenotypic difference is observed between the two groups, probably due to the different IGF2 expression pattern in target tissues.


Assuntos
Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Metilação de DNA , Impressão Genômica , Fator de Crescimento Insulin-Like II/genética , Mutação , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Masculino , Herança Paterna , Prognóstico , RNA Longo não Codificante/genética , Síndrome de Silver-Russell/genética , Síndrome de Silver-Russell/patologia , Adulto Jovem
20.
Behav Genet ; 50(1): 51-66, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493278

RESUMO

There is increasing interest within the genetics community in estimating the relative contribution of parental genetic effects on offspring phenotypes. Here we describe the user-friendly M-GCTA software package used to estimate the proportion of phenotypic variance explained by maternal (or alternatively paternal) and offspring genotypes on offspring phenotypes. The tool requires large studies where genome-wide genotype data are available on mother- (or alternatively father-) offspring pairs. The software includes several options for data cleaning and quality control, including the ability to detect and automatically remove cryptically related pairs of individuals. It also allows users to construct genetic relationship matrices indexing genetic similarity across the genome between parents and offspring, enabling the estimation of variance explained by maternal (or alternatively paternal) and offspring genetic effects. We evaluated the performance of the software using a range of data simulations and estimated the computing time and memory requirements. We demonstrate the use of M-GCTA on previously analyzed birth weight data from two large population based birth cohorts, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother and Child Cohort Study (MoBa). We show how genetic variation in birth weight is predominantly explained by fetal genetic rather than maternal genetic sources of variation.


Assuntos
Peso ao Nascer/genética , Previsões/métodos , Criança , Estudos de Coortes , Simulação por Computador , Pai , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Estudos Longitudinais , Masculino , Herança Materna/fisiologia , Modelos Genéticos , Mães , Pais , Herança Paterna/fisiologia , Fenótipo , Software
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