Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan.
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ABSTRACT:
SUBMITTER: Hollis B
PROVIDER: S-EPMC7093467 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 × 10(-70)) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 × 10(-12)). We find five novel loci for puberty timing (P<5 × 10(-8)), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease.
| S-EPMC4667609 | biostudies-literature
Project description:BackgroundIn bovines, there are significant differences within and among beef breeds in the time when bulls reach puberty. Although the timing of puberty is likely to be a multigenic trait, previous studies indicate that there may also be single genes that exert major effects on the timing of puberty within the general population. Despite its economic importance, there are not many SNPs or genetic markers associated with the age of puberty in male cattle. In the present work, we selected three candidate genes, GNRHR, LHR and IGF1, and associated their polymorphisms with the age of puberty in Angus male cattle.ResultsAfter weaning, 276 Angus males were measured every month for weight (W), scrotal circumference (SC), sperm concentration (C) and percentage of motility (M). A total of 4 SNPs, two within GNRHR, one in LHR and one in IGF1 were genotyped using the pyrosequencing technique. IGF1-SnaBI SNP was significant associated (P < 0.01) with age at SC 28 cm, but it were not associated with age at M 10% and C 50 million. Genotype CC exhibited an average age at SC 28 cm of 7 and 11 days higher than CT (p = 0.037) and TT (p = 0.012), respectively. This SNP explained 1.5% of the genetic variance of age of puberty at SC28. LHR-I499L, GNRHR-SNP5 and GNRHR-SNP6 were not associated with any of the measurements. However, GNRHR haplotypes showed a suggestive association with age at SC 28 cm.ConclusionsThe findings presented here could support the hypothesis that IGF1 is a regulator of the arrival to puberty in male calves and is involved in the events that precede and initiate puberty in bull calves. Given that most studies in cattle, as well as in other mammals, were done in female, the present results are the first evidence of markers associated with age at puberty in male cattle.
| S-EPMC3344682 | biostudies-literature
Project description:PurposeTestosterone analysis in hair allows for retrospective evaluation of endogenous testosterone concentrations, but studies devoted to investigating confounders in hair testosterone analysis have hitherto been scarce. The current study examined the stability of testosterone concentrations between two hair samples collected three months apart and investigated two potential confounding factors: natural hair colour and cosmetic hair treatments.MethodsTestosterone was analysed with an in-house radioimmunoassay with a limit of detection adequate for the purpose.ResultsThe testosterone concentrations from the two samplings, at baseline and three months later, had an intra-individual correlation of moderate strength (rho = 0.378, p<0.001, n = 146). Hair treatment, such as colouring or bleaching, seemed to increase testosterone concentrations (p = 0.051, n = 191, and in a paired analysis in a subset of the cohort p = 0.005, n = 24), while no effect of natural colour in untreated hair (p = 0.133) could be detected.ConclusionThe current results suggest that cosmetic hair treatments need to be considered in hair testosterone analyses and demonstrate the utility of a radioimmunoassay to reliably measure testosterone concentrations in small hair samples in women.
| S-EPMC10566713 | biostudies-literature
Project description:Understanding the regulation of puberty timing has relevance to developmental and human biology and to the pathogenesis of various diseases. Recent large-scale genome-wide association studies on puberty timing and adult height, body mass index (BMI) and central body shape provide evidence for shared biological mechanisms that regulate these traits. There is a substantial genetic overlap between age at menarche in women and BMI, with almost invariable directional consistency with the epidemiological associations between earlier menarche and higher BMI. By contrast, the genetic loci identified for age at menarche are largely distinct from those identified for central body shape, while alleles that confer earlier menarche can be associated with taller or shorter adult height. The findings of population-based studies on age at menarche show increasing relevance for other studies of rare monogenic disorders and enrich our understanding of the mechanisms that regulate the timing of puberty and reproductive function.
| S-EPMC6309186 | biostudies-literature
Project description:Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus, a marine midge whose reproduction is timed by circadian and circalunar clocks. Midges from different locations show strain-specific genetic timing adaptations. We examined genetic variation in five C. marinus strains from different locations and mapped quantitative trait loci for circalunar and circadian chronotypes. The region most strongly associated with circadian chronotypes generates strain-specific differences in the abundance of calcium/calmodulin-dependent kinase II.1 (CaMKII.1) splice variants. As equivalent variants were shown to alter CaMKII activity in Drosophila melanogaster, and C. marinus (Cma)-CaMKII.1 increases the transcriptional activity of the dimer of the circadian proteins Cma-CLOCK and Cma-CYCLE, we suggest that modulation of alternative splicing is a mechanism for natural adaptation in circadian timing.
| S-EPMC5133387 | biostudies-literature
Project description:Delayed pubertal onset has many etiologies, but on average two-thirds of patients presenting with late puberty have self-limited (or constitutional) delayed puberty. Self-limited delayed puberty often has a strong familial basis. Segregation analyses from previous studies show complex models of inheritance, most commonly autosomal dominant, but also including autosomal recessive, bilineal, and X-linked. Sporadic cases are also observed. Despite this, the neuroendocrine mechanisms and genetic regulation remain unclear in the majority of patients with self-limited delayed puberty. Only rarely have mutations in genes known to cause aberrations of the hypothalamic-pituitary-gonadal axis been identified in cases of delayed puberty, and the majority of these are in relatives of patients with congenital hypogonadotropic hypogonadism (CHH), for example in the FGFR1 and GNRHR genes. Using next generation sequencing in a large family with isolated self-limited delayed puberty, a pathogenic mutation in the CHH gene HS6ST1 was found as the likely cause for this phenotype. Additionally, a study comparing the frequency of mutations in genes that cause GnRH deficiency between probands with CHH and probands with isolated self-limited delayed puberty identified that a significantly higher proportion of mutations with a greater degree of oligogenicity were seen in the CHH group. Mutations in the gene IGSF10 have been implicated in the pathogenesis of familial late puberty in a large Finnish cohort. IGSF10 disruption represents a fetal origin of delayed puberty, with dysregulation of GnRH neuronal migration during embryonic development presenting for the first time in adolescence as late puberty. Some patients with self-limited delayed puberty have distinct constitutional features of growth and puberty. Deleterious variants in FTO have been found in families with delayed puberty with extremely low BMI and maturational delay in growth in early childhood. Recent exciting evidence highlights the importance of epigenetic up-regulation of GnRH transcription by a network of miRNAs and transcription factors, including EAP1, during puberty. Whilst a fascinating heterogeneity of genetic defects have been shown to result in delayed and disordered puberty, and many are yet to be discovered, genetic testing may become a realistic diagnostic tool for the differentiation of conditions of delayed puberty.
| S-EPMC6606719 | biostudies-literature
Project description:Quinoa is an agriculturally important crop species originally domesticated in the Andes of central South America. One of its most important phenotypic traits is seed colour. Seed colour variation is determined by contrasting abundance of betalains, a class of strong antioxidant and free radicals scavenging colour pigments only found in plants of the order Caryophyllales. However, the genetic basis for these pigments in seeds remains to be identified. Here we demonstrate the application of machine learning (extreme gradient boosting) to identify genetic variants predictive of seed colour. We show that extreme gradient boosting outperforms the classical genome-wide association approach. We provide re-sequencing and phenotypic data for 156 South American quinoa accessions and identify candidate genes potentially controlling betalain content in quinoa seeds. Genes identified include novel cytochrome P450 genes and known members of the betalain synthesis pathway, as well as genes annotated as being involved in seed development. Our work showcases the power of modern machine learning methods to extract biologically meaningful information from large sequencing data sets.
| S-EPMC11022794 | biostudies-literature
Project description:The factors that trigger human puberty are among the central mysteries of reproductive biology. Several approaches, including mutational analysis of candidate genes, large-scale genome-wide association studies, whole exome sequencing, and whole genome sequencing have been performed in attempts to identify novel genetic factors that modulate the human hypothalamic-pituitary-gonadal axis to result in premature sexual development. Genetic abnormalities involving excitatory and inhibitory pathways regulating gonadotropin-releasing hormone secretion, represented by the kisspeptin (KISS1 and KISS1R) and makorin ring finger 3 (MKRN3) systems, respectively, have been associated with sporadic and familial cases of central precocious puberty (CPP). More recently, paternally inherited genetic defects of DLK1 were identified in four families with nonsyndromic CPP and a metabolic phenotype. DLK1 encodes a transmembrane protein that is important for adipose tissue homeostasis and neurogenesis and is located in the imprinted chromosome 14q32 region associated with Temple syndrome. In this review, we highlight the clinical and genetic features of patients with CPP caused by DLK1 mutations and explore the involvement of Notch signaling and DLK1 in the control of pubertal onset.
| S-EPMC8585528 | biostudies-literature
Project description:Cucurbita pepo is high susceptible to Zucchini yellow mosaic virus (ZYMV) and the resistance found in several wild species does not provide complete or broad-spectrum resistance. In this study, a source of tolerance introgressed in C. pepo (381e) from C. moschata, in True French (TF) background, was investigated 12 days after inoculation (DPI) at transcriptomic and genomic levels. A comparative RNA-seq experiment, allowed to evaluate more than 33,000 expressed transcripts and to identify 146 differentially expressed genes (DEGs) in 381e, mainly involved in photosynthesis, transcription, cytoskeleton organization and callose synthesis. By contrast, the susceptible line True French triggered oxidative processes related to response to biotic stimulus and two synaptotagmin (SYTA) genes, key regulators of plant virus intercellular movement. Finally, transcripts mapping allowed the identification of two regions rich in SNPs (Single Nucleotide Polymorphisms) on linkage group 1 and linkage group 8, putatively introgressed from C. moschata, containing a putative disease resistance protein (CNL gene) exclusively expressed in 381e. In conclusion, 381e transcriptome analysis confirmed a globally improved plant fitness by reducing the effect of viral infection and showed the activation of genes putatively involved in tolerance to ZYMV. Our work provides new insight into plant virus recovery process to ZYMV.
2020-10-20 | GSE159530 | GEO
Project description:Little is known about genes regulating male puberty. Further, while many identified pubertal timing variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9 × 10(-9)), a menarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6 × 10(-5)) and short adult stature (p = 7.5 × 10(-6)) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies.
| S-EPMC4168307 | biostudies-literature