Chromosomal Genotypes Research Articles

The role of gonadal hormones and sex chromosomes in sex-dependent effects of early nutrition on metabolic health.

Early-life conditions such as prenatal nutrition can have long-term effects on metabolic health, and these effects may differ between males and females. Understanding the biological mechanisms underlying sex differences in the response to early-life environment will improve interventions, but few such mechanisms have been identified, and there is no overall framework for understanding sex differences. Biological sex differences may be due to chromosomal sex, gonadal sex, or interactions between the two. This review describes approaches to distinguish between the roles of chromosomal and gonadal sex, and summarizes findings regarding sex differences in metabolism. The Four Core Genotypes (FCG) mouse model allows dissociation of the sex chromosome genotype from gonadal type, whereas the XY* mouse model can be used to distinguish effects of X chromosome dosage vs the presence of the Y chromosome. Gonadectomy can be used to distinguish between organizational (permanent) and activational (reversible) effects of sex hormones. Baseline sex differences in a variety of metabolic traits are influenced by both activational and organizational effects of gonadal hormones, as well as sex chromosome complement. Thus far, these approaches have not been widely applied to examine sex-dependent effects of prenatal conditions, although a number of studies have found activational effects of estradiol to be protective against the development of hypertension following early-life adversity. Genes that escape X chromosome inactivation (XCI), such as Kdm5c, contribute to baseline sex-differences in metabolism, while Ogt, another XCI escapee, leads to sex-dependent responses to prenatal maternal stress. Genome-wide approaches to the study of sex differences include mapping genetic loci influencing metabolic traits in a sex-dependent manner. Seeking enrichment for binding sites of hormone receptors among genes showing sexually-dimorphic expression can elucidate the relative roles of hormones. Using the approaches described herein to identify mechanisms underlying sex-dependent effects of early nutrition on metabolic health may enable the identification of fundamental mechanisms and potential interventions.

Sex bias in celiac disease: XWAS and monocyte eQTLs in women identify TMEM187 as a functional candidate gene

BackgroundCeliac disease (CeD) is an immune-mediated disorder that develops in genetically predisposed individuals upon gluten consumption. HLA risk alleles explain 40% of the genetic component of CeD, so there have been continuing efforts to uncover non-HLA loci that can explain the remaining heritability. As in most autoimmune disorders, the prevalence of CeD is significantly higher in women. Here, we investigated the possible involvement of the X chromosome on the sex bias of CeD.MethodsWe performed a X chromosome-wide association study (XWAS) and a gene-based association study in women from the CeD Immunochip (7062 cases, 5446 controls). We also constructed a database of X chromosome cis-expression quantitative trait loci (eQTLs) in monocytes from unstimulated (n = 226) and lipopolysaccharide (LPS)-stimulated (n = 130) female donors and performed a Summary-data-based MR (SMR) analysis to integrate XWAS and eQTL information. We interrogated the expression of the potentially causal gene (TMEM187) in peripheral blood mononuclear cells (PBMCs) from celiac patients at onset, on a gluten-free diet, potential celiac patients and non-celiac controls.ResultsThe XWAS and gene-based analyses identified 13 SNPs and 25 genes, respectively, 22 of which had not been previously associated with CeD. The X chromosome cis-eQTL analysis found 18 genes with at least one cis-eQTL in naïve female monocytes and 8 genes in LPS-stimulated female monocytes, 2 of which were common to both situations and 6 were unique to LPS stimulation. SMR identified a potentially causal association of TMEM187 expression in naïve monocytes with CeD in women, regulated by CeD-associated, eQTL-SNPs rs7350355 and rs5945386. The CeD-risk alleles were correlated with lower TMEM187 expression. These results were replicated using eQTLs from LPS-stimulated monocytes. We observed higher levels of TMEM187 expression in PBMCs from female CeD patients at onset compared to female non-celiac controls, but not in male CeD individuals.ConclusionUsing X chromosome genotypes and gene expression data from female monocytes, SMR has identified TMEM187 as a potentially causal candidate in CeD. Further studies are needed to understand the implication of the X chromosome in the higher prevalence of CeD in women.

Computational identification of precision therapeutics for Alzheimer’s disease specific to endocrine and APOE genotype status

AbstractBackgroundAlzheimer’s disease (AD) affects 6.5 million people in the US, two‐thirds of which are women. Despite extensive research, there are currently no highly effective treatments for AD. The greatest risk factors for AD are age, chromosomal female sex and APOEε4 genotype. A key driver of chronological and endocrinological aging is the activation of innate and adaptive immune systems occurring in midlife female brain. To effectively prevent and treat AD, it is crucial to develop computational methods that take into account these factors and screen for personalized therapeutics.MethodRNAseq data of 15‐month acyclic vs 9‐month regular APOEε3/ε3 and APOEε4/ε4 female mouse models were analyzed to identify APOE‐specific Differentially Expressed Genes (DEGs, pvalue<.01). STRING Protein‐Protein Interaction (PPI) database was used to extract protein interactors for the two APOEε3/ε3 and APOEε4/ε4 DEG lists and construct two APOE‐specific AD PPI networks. Target Proteins (TPs) candidates in each network were identified using the DrugBank database by selecting only proteins targeted by at least one FDA‐approved drug. A score of drug synergy was developed to rank FDA‐approved drugs based on the number of target proteins in‐ vs out‐ of the APOE‐AD specific networks and their distance to DEG nodes.ResultFrom RNAseq analyses, we identified a total of 265 DEGs for APOEε3/ε3 and 452 DEGs for APOEε4/ε4 genotype. The APOE‐AD‐specific PPI networks resulted in 1,711 nodes (proteins) and 21,445 edges (PPIs) for the APOEε3/ε3 genotype and 2,841 nodes and 35,493 edges for APOEε4/ε4 genotype. Using the DrugBank database, 342 and 568 potential therapeutic targets were identified in the APOEε3/ε3 and APOEε4/ε4 networks, respectively. Finally, drug synergy score enabled ranking 99 therapeutics for APOEε3/ε3 network and 102 drugs for APOEε4/ε4 network, of which 19 resulted in both lists.ConclusionThis study presents a network‐based approach for identifying personalized therapeutics for AD based on endocrine transition changes and APOE genotype. The results suggest that there is greater transcriptomic dysregulation in female APOEε4/ε4 brains compared to APOEε3/ε3 brains. The proposed computational approach has the potential to advance precision medicine for the prevention and treatment of AD, and future research will focus on identifying the most effective combinations of therapeutics.

Heat exchanger circuitry optimization using an enhanced integer permutation-based genetic algorithm in low-GWP reversible heat pump applications

Tube-fin heat exchangers (HXs) are key components in air-conditioning and heat pump applications. Advanced heat exchanger design optimization tools are desired to adapt to the industrial transition from conventional refrigerants to low Global Warming Potential (low-GWP) refrigerants. The performance of heat exchangers is strongly influenced by the refrigerant circuitry. This research presents an enhanced integer permutation-based Genetic Algorithm (IPGA) to optimize the circuitry of tube-fin heat exchangers. To remedy the limitation of the previous IPGA, which cannot generate designs with splitting and merging of circuits, a new chromosome, as well as new generic operators, are developed. The enhanced IPGA uses effective chromosome representations and GA operators to guarantee the chromosome (genotype) can be mapped to valid heat exchanger designs (phenotype) and incorporates real-world manufacturability constraints to ensure the optimal designs are manufacturable with the available tooling. Previous circuitry optimizations focus on improving component-level performance under a specific operating condition, i.e., the heat exchanger either works as a condenser or an evaporator. The optimal circuitry obtained under air conditioning (AC) mode cannot guarantee optimal performance when used in heat pump (HP) mode. To improve the dual-mode performance of reversible heat pumps, a bi-objective optimization problem formulation is implemented to achieve optimal system performance in both AC and HP modes. A case study using six refrigerants, i.e., R410A, R452B, R454B, R32, D2Y60, and L41a, shows that optimal heat exchangers yield up to 6.1 % energy efficiency ratio (EER) improvement under AC mode and up to 8.5 % coefficient of performance (COP) improvement under HP mode. The use of this design approach can ensure a preferable performance of reversible heat pumps during both cooling and heating modes.

Continuous transcriptome analysis reveals novel patterns of early gene expression in Drosophila embryos.

The transformative events during early organismal development lay the foundation for body formation and long-term phenotype. The rapid progression of events and the limited material available present major barriers to studying these earliest stages of development. Herein, we report an operationally simple RNA sequencing approach for high-resolution, time-sensitive transcriptome analysis in early (≤3 h) Drosophila embryos. This method does not require embryo staging but relies on single-embryo RNA sequencing and transcriptome ordering along a developmental trajectory (pseudo-time). The resulting high-resolution, time-sensitive mRNA expression profiles reveal the exact onset of transcription and degradation for thousands of transcripts. Further, using sex-specific transcription signatures, embryos can be sexed directly, eliminating the need for Y chromosome genotyping and revealing patterns of sex-biased transcription from the beginning of zygotic transcription. Our data provide an unparalleled resolution of gene expression during early development and enhance the current understanding of early transcriptional processes.

Neo-sex chromosome evolution shapes sex-dependent asymmetrical introgression barrier

Sex chromosomes play a special role in the evolution of reproductive barriers between species. Here we describe conflicting roles of nascent sex chromosomes on patterns of introgression in an experimental hybrid swarm. Drosophila nasuta and Drosophila albomicans are recently diverged, fully fertile sister species that have different sex chromosome systems. The fusion between an autosome (Muller CD) with the ancestral X and Y gave rise to neo-sex chromosomes in D. albomicans, while Muller CD remains unfused in D. nasuta. We found that a large block containing overlapping inversions on the neo-sex chromosome stood out as the strongest barrier to introgression. Intriguingly, the neo-sex chromosome introgression barrier is asymmetrical and sex-dependent. Female hybrids showed significant D. albomicans–biased introgression on Muller CD (neo-X excess), while males showed heterosis with excessive (neo-X, D. nasuta Muller CD) genotypes. We used a population genetic model to dissect the interplay of sex chromosome drive, heterospecific pairing incompatibility between the neo-sex chromosomes and unfused Muller CD, neo-Y disadvantage, and neo-X advantage in generating the observed sex chromosome genotypes in females and males. We show that moderate neo-Y disadvantage and D. albomicans specific meiotic drive are required to observe female-specific D. albomicans–biased introgression in this system, together with pairing incompatibility and neo-X advantage. In conclusion, this hybrid swarm between a young species pair sheds light onto the multifaceted roles of neo-sex chromosomes in a sex-dependent asymmetrical introgression barrier at a species boundary.

Germline sex determination regulates sex-specific signaling between germline stem cells and their niche.

Establishing germ cell sexual identity is critical for development of male and female germline stem cells (GSCs) and production of sperm or eggs. Germ cells depend on signals from the somatic gonad to determine sex, but in organisms such as flies, mice, and humans, the sex chromosome genotype of the germ cells is also important for germline sexual development. How somatic signals and germ-cell-intrinsic cues combine to regulate germline sex determination is thus a key question. We find that JAK/STAT signaling in the GSC niche promotes male identity in germ cells, in part by activating the chromatin reader Phf7. Further, we find that JAK/STAT signaling is blocked in XX (female) germ cells through the action of the sex determination gene Sex lethal to preserve female identity. Thus, an important function of germline sexual identity is to control how GSCs respond to signals in their niche environment.

Familial intragenic X-linked OPHN1 gene deletion in a newborn male infant with low birth weight and distinctive facial appearance that diagnosed by advanced microarray-CGH method

The oligophrenin-1 (OPHN1) gene is localized in the Xq12 region and it encodes the rho-GTPase-activating protein which spans 500 kb in size and consists of 25 exons. Gene plays crucial role in synaptic function and dendritic morphogenesis. Here we report a 391 kb deletion in OPHN1 gene in a mother and her newborn male child with recognizable pattern of clinical and neuroradiological hallmarks. Mother has short stature, and her son has distinctive facial appearance, bilateral choroid plexus cysts and low birth weight (1600 g). After clinical evaluation, the current large intragenic gene deletion was identified by microarray-CGH and confirmed by MLPA techniques. The P106 MRX probemix kit (MRC Holland C1- 0416, Amsterdam) and Coffalyser software were used for MLPA and Agilent sure print G3 HUMAN CGH 60k Microarray platform and Agilent cytogenomics 4.0.2.21 software (Singapore) were used for advance chromosomal genotyping for mother and his son in the presented results. Presented results showed that mother with X chromosome deletion has a great risk to have a son with mental retardation due to deleted X chromosome transmission in 50% possibility. If the son has clinical findings, the genotype should be screened by using the advanced genetic methodology. Results also showed that once these cases are first diagnosed correctly, they may be candidate to IVF for preimplantation genetic diagnosis by giving appropriate genetic counseling. It is also comment that pregnant women who have the history of having X-linked mental retarded child or a mentally retarded brother need to be tested genetically for prenatal diagnosis.

Temperature-dependent effects of house fly proto-Y chromosomes on gene expression could be responsible for fitness differences that maintain polygenic sex determination.

Sex determination, the developmental process by which sexually dimorphic phenotypes are established, evolves fast. Evolutionary turnover in a sex determination pathway may occur via selection on alleles that are genetically linked to a new master sex determining locus on a newly formed proto-sex chromosome. Species with polygenic sex determination, in which master regulatory genes are found on multiple different proto-sex chromosomes, are informative models to study the evolution of sex determination and sex chromosomes. House flies are such a model system, with male determining loci possible on all six chromosomes and a female-determiner on one of the chromosomes as well. The two most common male-determining proto-Y chromosomes form latitudinal clines on multiple continents, suggesting that temperature variation is an important selection pressure responsible for maintaining polygenic sex determination in this species. Temperature-dependent fitness effects could be manifested through temperature-dependent gene expression differences across proto-Y chromosome genotypes. These gene expression differences may be the result of cis regulatory variants that affect the expression of genes on the proto-sex chromosomes, or trans effects of the proto-Y chromosomes on genes elswhere in the genome. We used RNA-seq to identify genes whose expression depends on proto-Y chromosome genotype and temperature in adult male house flies. We found no evidence for ecologically meaningful temperature-dependent expression differences of sex determining genes between male genotypes, but we were probably not sampling an appropriate developmental time-point to identify such effects. In contrast, we identified many other genes whose expression depends on the interaction between proto-Y chromosome genotype and temperature, including genes that encode proteins involved in reproduction, metabolism, lifespan, stress response, and immunity. Notably, genes with genotype-by-temperature interactions on expression were not enriched on the proto-sex chromosomes. Moreover, there was no evidence that temperature-dependent expression is driven by chromosome-wide cis-regulatory divergence between the proto-Y and proto-X alleles. Therefore, if temperature-dependent gene expression is responsible for differences in phenotypes and fitness of proto-Y genotypes across house fly populations, these effects are driven by a small number of temperature-dependent alleles on the proto-Y chromosomes that may have trans effects on the expression of genes on other chromosomes.

Evaluating evidence of mitonuclear incompatibilities with the sex chromosomes in an avian hybrid zone.

The exploration of hybrid zones and the intergenomic conflicts exposed through hybridization provide windows into the processes of divergence and speciation. Sex chromosomes and mitonuclear incompatibilities have strong associations with the genetics of hybrid dysfunction. In ZW sex-determining systems, maternal co-inheritance of the mitochondrial and W chromosomes immediately exposes incompatibilities between these maternal contributions of one species and the Z chromosome of another. We analyze mitochondrial and Z chromosome admixture in the long-tailed finch (Poephila acuticauda) of Australia, where hybridizing subspecies differ prominently in Z chromosome genotype and in bill color, yet the respective centers of geographic admixture for these two traits are offset by 350 km. We report two well-defined mitochondrial clades that diverged ∼0.5 million years ago. Mitochondrial contact is geographically co-located within a hybrid zone of Z chromosome admixture and is displaced from bill color admixture by nearly 400 km. Consistent with Haldane's rule expectations, hybrid zone females are significantly less likely than males to carry an admixed Z chromosome or have mismatched Z-mitochondrial genotypes. Furthermore, there are significantly fewer than expected mitonuclear mismatches in hybrid zone females and paternal backcross males. Results suggest a potential for mitonuclear/sex chromosome incompatibilities in the emergence of reproductive isolation in this system.

­­­Germline Sex Determination Regulates Sex-Specific Signaling Between Germline Stem Cells and Their Niche

The establishment of sexual identity in germ cells is critical for the development of male and female germline stem cells (GSCs) and production of sperm vs. eggs. Thus, this process is essential for sexual reproduction and human fertility. Germ cells depend on signals from the somatic gonad to determine their sex, but in organisms such as flies, mice and humans, the sex chromosome genotype of the germ cells is also important for germline sexual development. How somatic signals and germ cell-intrinsic cues act together to regulate germline sex determination is a key question about which little is known. We have found that JAK/STAT signaling in the GSC niche promotes male identity in germ cells and GSCs, in part by activating expression of the epigenetic reader Phf7. We have also found that JAK/STAT signaling is blocked in XX (female) germ cells through the intrinsic action of the sex determination gene Sex lethal, which preserves female identity. Thus, an important function of germline sexual identity is to control how GSCs respond to signals in their niche environment.

Simple inheritance, complex regulation: Supergene-mediated fire ant queen polymorphism.

The fire ant Solenopsis invicta exists in two alternate social forms: monogyne nests contain a single reproductive queen and polygyne nests contain multiple reproductive queens. This colony-level social polymorphism corresponds with individual differences in queen physiology, queen dispersal patterns and worker discrimination behaviours, all evidently regulated by an inversion-based supergene that spans more than 13Mb of a "social chromosome," contains over 400 protein-coding genes and rarely undergoes recombination. The specific mechanisms by which this supergene influences expression of the many distinctive features that characterize the alternate forms remain almost wholly unknown. To advance our understanding of these mechanisms, we explore the effects of social chromosome genotype and natal colony social form on gene expression in queens sampled as they embarked on nuptial flights, using RNA-sequencing of brains and ovaries. We observe a large effect of natal social form, that is, of the social/developmental environment, on gene expression profiles, with similarly substantial effects of genotype, including: (a) supergene-associated gene upregulation, (b) allele-specific expression and (c) pronounced extra-supergene trans-regulatory effects. These findings, along with observed spatial variation in differential and allele-specific expression within the supergene region, highlight the complex gene regulatory landscape that emerged following divergence of the inversion-mediated Sb haplotype from its homologue, which presumably largely retained the ancestral gene order. The distinctive supergene-associated gene expression trajectories we document at the onset of a queen's reproductive life expand the known record of relevant molecular correlates of a complex social polymorphism and point to putative genetic factors underpinning the alternate social syndromes.

Examination of the genetic factors underlying the cognitive variability associated with neurofibromatosis type 1

PurposeNeurofibromatosis type 1 (NF1) is an autosomal dominant disorder associated with cognitive deficits. The NF1 cognitive phenotype is generally considered to be highly variable, possibly due to the observed T2-weighted hyperintensities, loss of heterozygosity, NF1-specific genetic modifiers, or allelic imbalance. MethodsWe investigated cognitive variability and assessed the contribution of genetic factors by performing a retrospective cohort study and a monozygotic twin case series. We included data of 497 children with genetically confirmed NF1 and an IQ assessment, including 12 monozygotic twin and 17 sibling sets. ResultsIndividuals carrying an NF1 chromosomal microdeletion showed significant lower full-scale IQ (FSIQ) scores than individuals carrying intragenic pathogenic NF1 variants. For the intragenic subgroup, the variability in cognitive ability and the correlation of IQ between monozygotic NF1 twin pairs or between NF1 siblings is similar to the general population. ConclusionsThe variance and heritability of IQ in individuals with NF1 are similar to that of the general population, and hence mostly driven by genetic background differences. The only factor that significantly attenuates IQ in NF1 individuals is the NF1 chromosomal microdeletion genotype. Implications for clinical management are that individuals with intragenic NF1 variants that score <1.5–2 SD below the mean of the NF1 population should be screened for additional causes of cognitive disability.

Malocclusion and Hair Loss: An Intimate Relationship

In the dental industry, it seem no one has entertained the thought that if a dislocated mandible, in a Class II Skeletal relation could occlude or block the blood flow in in the STA.* Therefore stopping or impeding blood flow to the vertex of the head and therefor causing balding. Taking into consideration that in a healthy Class I Skeletal relation the clearance between the base of the skull and the eminence of the condyle is only 3.5mm.Pic 1 Orthodontic experience tells us that mandibles 3.5mm retrognathic and more are very common. The intent of this paper is to expose the facts and evidence that show the Class II Skeletal mandible is the cause of balding by blocking blood flow through the S.T.A. Balding of vertex can be avoided. A large array of research has been, and continues to be conducted to determine the causative agent for hair loss. Traditionally such investigation has focused on a number of varying topics, including but not limited to chromosome composition, genotype, and subsequent phenotype expression. However, little or no investigation has been conducted to deduce what effect the skeletal relationship has upon the initial development of hair loss. Through a series of observational case studies, it is evident that there is a relationship between malocclusion and hair loss. Specifically, through analysis of dental records, cephalometric radiographs, and visual observation of patients, there appears to be a correlation between Class II Skeletal malocclusion and subsequent hair loss. Further investigation yields that vascular anatomical differences between different skeletal schemes is associated with the development of hair loss. &#x0D; Keywords: Craniofacial Anomalies, Pediatric Dentistry, Orthodontics, Hair Loss, Baldness

Malocclusion and Hair Loss: An Intimate Relationship

A large array of research has been, and continues to be conducted to determine the causative agent for hair loss. Traditionally such investigation has focused on a number of varying topics, including but not limited to chromosome composition, genotype, and subsequent phenotype expression. However, little or no investigation has been conducted to deduce what effect the skeletal relationship has upon the initial development of hair loss. Through a series of observational case studies, it is evident that there is a relationship between malocclusion and hair loss. Specifically, through analysis of dental records, cephalometric radiographs, and visual observation of patients, there appears to be a correlation between Class II Skeletal malocclusion and subsequent hair loss. Further investigation yields that vascular anatomical differences between different skeletal schemes is associated with the development of hair loss

Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice.

Late onset Alzheimer’s disease (LOAD) is a progressive neurodegenerative disease with four well-established risk factors: age, APOE4 genotype, female chromosomal sex, and maternal history of AD. Each risk factor impacts multiple systems, making LOAD a complex systems biology challenge. To investigate interactions between LOAD risk factors, we performed multiple scale analyses, including metabolomics, transcriptomics, brain magnetic resonance imaging (MRI), and beta-amyloid assessment, in 16 months old male and female mice with humanized human APOE3 (hAPOE3) or APOE4 (hAPOE4) genes. Metabolomic analyses indicated a sex difference in plasma profile whereas APOE genotype determined brain metabolic profile. Consistent with the brain metabolome, gene and pathway-based RNA-Seq analyses of the hippocampus indicated increased expression of fatty acid/lipid metabolism related genes and pathways in both hAPOE4 males and females. Further, female transcription of fatty acid and amino acids pathways were significantly different from males. MRI based imaging analyses indicated that in multiple white matter tracts, hAPOE4 males and females exhibited lower fractional anisotropy than their hAPOE3 counterparts, suggesting a lower level of white matter integrity in hAPOE4 mice. Consistent with the brain metabolomic and transcriptomic profile of hAPOE4 carriers, beta-amyloid generation was detectable in 16-month-old male and female brains. These data provide therapeutic targets based on chromosomal sex and APOE genotype. Collectively, these data provide a framework for developing precision medicine interventions during the prodromal phase of LOAD, when the potential to reverse, prevent and delay LOAD progression is greatest.

Paternal Y chromosomal genotyping reveals multiple large-scale admixtures in the formation of Lolo-Burmese–speaking populations in southwest China

Background: Bai and Yi people are two Tibeto-Burman speaking ethnic groups in Yunnan, southwest China. The genetic structure and history of these two groups are largely unknown due to a lack of available genetic data.Aim: To investigate the paternal genetic structure and population relationship of the Yi and Bai people.Subjects and methods: We collected samples from 278 Bai individuals and 283 Yi individuals from Yunnan and subsequently genotyped 43 phylogenetically relevant Y-SNPs in those samples. We estimated haplogroup frequencies and merged our data with a reference database including 46 representative worldwide populations to infer genetic relationships.Results: Y chromosomal haplogroup O-M175 is the dominant lineage in both Bai and Yi people. The Bai and Yi show a close genetic relationship with other Tibeto-Burman–speaking populations with high frequencies of haplogroup O2a2b1a1-Page23, which is also confirmed by PCA. The frequencies of the Tai-Kadai specific lineage O1a-M119, the southern China widespread lineage O1b-P31 and the eastern China enriched lineage O2a1b-002611, are also relatively high in our studied populations.Conclusions: The paternal Y chromosomal affinity of the Bai and Yi with Tibeto-Burman groups is consistent with the language classification. During the formation of the Bai and Yi populations, there were multiple large-scale admixtures, including the expansion of Neolithic farming populations from northern China, the assimilation of Tai-Kadai–speaking populations in southwest China, the demographic expansion driven by Neolithic agricultural revolution from southern China, and the admixture with populations of military immigration from northern and eastern China.

A Historical-Genetic Reconstruction of Human Extra-Pair Paternity.

Paternity testing using genetic markers has shown that extra-pair paternity (EPP) is common in many pair-bonded species [1, 2]. Evolutionary theory and empirical data show that extra-pair copulations can increase the fitness of males as well as females [3,4]. This can carry a significant fitness cost for the social father, who then invests in rearing offspring that biologically are not his own [5]. In human populations, the incidence and correlates of extra-pair paternity remain highly contentious [2, 6, 7]. Here, we use a population-level genetic genealogy approach [6, 8] to reconstruct spatiotemporal patterns in human EPP rates. Using patrilineal genealogies from the Low Countries spanning a period of over 500 years and Y chromosome genotyping of living descendants, our analysis reveals that historical EPP rates, while low overall, were strongly impacted by socioeconomic and demographic factors. Specifically, we observe that estimated EPP rates among married couples varied by more than an order of magnitude, from 0.4% to 5.9%, and peaked among families with a low socioeconomic background living in densely populated cities of the late 19th century. Our results support theoretical predictions that social context can strongly affect the outcomes of sexual conflict in human populations by modulating the incentives and opportunities for engaging in extra-pair relationships [9-11]. These findings show how contemporary genetic data combined with in-depth genealogies open up a new window on the sexual behavior of our ancestors.

Minimal Effects of Proto-Y Chromosomes on House Fly Gene Expression in Spite of Evidence that Selection Maintains Stable Polygenic Sex Determination.

Sex determination, the developmental process by which organismal sex is established, evolves fast, often due to changes in the master regulators at the top of the pathway. Additionally, in species with polygenic sex determination, multiple different master regulators segregate as polymorphisms. Understanding the forces that maintain polygenic sex determination can be informative of the factors that drive the evolution of sex determination. The house fly, Musca domestica, is a well-suited model to those ends because natural populations harbor male-determining loci on each of the six chromosomes and a biallelic female determiner. To investigate how natural selection maintains polygenic sex determination in the house fly, we assayed the phenotypic effects of proto-Y chromosomes by performing mRNA-sequencing experiments to measure gene expression in house fly males carrying different proto-Y chromosomes. We find that the proto-Y chromosomes have similar effects as a nonsex-determining autosome. In addition, we created sex-reversed males without any proto-Y chromosomes and they had nearly identical gene expression profiles as genotypic males. Therefore, the proto-Y chromosomes have a minor effect on male gene expression, consistent with previously described minimal X-Y sequence differences. Despite these minimal differences, we find evidence for a disproportionate effect of one proto-Y chromosome on male-biased expression, which could be partially responsible for fitness differences between males with different proto-Y chromosome genotypes. Therefore our results suggest that, if natural selection maintains polygenic sex determination in house fly via gene expression differences, the phenotypes under selection likely depend on a small number of genetic targets.

X chromosome genetic data in a Spanish children cohort, dataset description and analysis pipeline

X chromosome genetic variation has been proposed as a potential source of missing heritability for many complex diseases, including obesity. Currently, there is a lack of public available genetic datasets incorporating X chromosome genotype data. Although several X chromosome-specific statistics have been developed, there is also a lack of readily available implementations for routine analysis. Here, we aimed: (1) to make public and describe a dataset incorporating phenotype and X chromosome genotype data from a cohort of 915 normal-weight, overweight and obese children, and (2) to deeply describe a whole implementation of the special X chromosome analytic process in genetics. Datasets and pipelines like this are crucial to get familiar with the steps in which X chromosome requires special attention and may raise awareness of the importance of this genomic region.