Evaluation of truncating variants in the LCORL gene in relation to body size of goats from Switzerland.
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ABSTRACT:
SUBMITTER: Graber JK
PROVIDER: S-EPMC9305788 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Body size is an important characteristic for horses of various breeds and essential for the classification of ponies concerning the limit value of 148 cm (58.27 inches) height at the withers. Genome-wide association analyses revealed the highest associated quantitative trait locus for height at the withers on horse chromosome (ECA) 3 upstream of the candidate gene LCORL. Using 214 Hanoverian horses genotyped on the Illumina equine SNP50 BeadChip and 42 different horse breeds across all size ranges, we confirmed the highly associated single nucleotide polymorphism BIEC2-808543 (-log(10)P = 8.3) and the adjacent gene LCORL as the most promising candidate for body size. We investigated the relative expression levels of LCORL and its two neighbouring genes NCAPG and DCAF16 using quantitative real-time PCR (RT-qPCR). We could demonstrate a significant association of the relative LCORL expression levels with the size of the horses and the BIEC2-808543 genotypes within and across horse breeds. In heterozygous C/T-horses expression levels of LCORL were significantly decreased by 40% and in homozygous C/C-horses by 56% relative to the smaller T/T-horses. Bioinformatic analyses indicated that this SNP T>C mutation is disrupting a putative binding site of the transcription factor TFIID which is important for the transcription process of genes involved in skeletal bone development. Thus, our findings suggest that expression levels of LCORL play a key role for body size within and across horse breeds and regulation of the expression of LCORL is associated with genetic variants of BIEC2-808543. This is the first functional study for a body size regulating polymorphism in horses and a further step to unravel the mechanisms for understanding the genetic regulation of body size in horses.
| S-EPMC3572084 | biostudies-literature
Project description:BackgroundKisspeptins are the peptide products of KISS1 gene, which operate via the G - protein-coupled receptor GPR54. These peptides have emerged as essential upstream regulators of neurons secreting gonadotropin-releasing hormone (GnRH), the major hypothalamic node for the stimulatory control of the hypothalamic-pituitary- gonadal (HPG) axis. The present study detected the polymorphisms of caprine KISS1 gene in three goat breeds and investigated the associations between these genetic markers and litter size.ResultsThree goat breeds (n = 680) were used to detect single nucleotide polymorphisms (SNPs) in the coding regions with their intron-exon boundaries and the proximal flanking regions of KISS1 gene by DNA sequencing and PCR-RFLP. Eleven novel SNPs (g.384G>A, g.1147T>C, g.1417G>A, g.1428_1429delG, g.2124C>T, g.2270C>T, g.2489T>C, g.2510G>A, g.2540C>T, g.3864_3865delCA and g.3885_3886insACCCC) were identified. It was shown that Xinong Saanen and Guanzhong goat breeds were in Hardy-Weinberg disequilibrium at g.384G>A locus (P < 0.05). Both g.2510G>A and g.2540C>T loci were closely linked in Xinong Saanen (SN), Guanzhong (GZ) and Boer (BG) goat breeds (r² > 0.33). The g.384G>A, g.2489T>C, g.2510G>A and g.2540C>T SNPs were associated with litter size (P<0.05). Individuals with AATTAATT combinative genotype of SN breed (SC) and TTAATT combinative genotype of BG breed (BC) had higher litter size than those with other combinative genotypes in average parity. The results extend the spectrum of genetic variation of the caprine KISS1 gene, which might contribute to goat genetic resources and breeding.ConclusionsThis study explored the genetic polymorphism of KISS1 gene, and indicated that four SNPs may play an important role in litter size. Their genetic mechanism of reproduction in goat breeds should be further investigated. The female goats with SC1 (AATTAATT) and BC7 (TTAATT) had higher litter size than those with other combinative genotypes in average parity and could be used for the development of new breeds of prolific goats. Further research on a large number of animals is required to confirm the link with increased prolificacy in goats.
| S-EPMC3734198 | biostudies-literature
Project description:Several studies have shown the association between the ligand-dependent nuclear receptor compression-like protein (LCORL) gene and body size in horses, pigs and donkeys. Based on previous studies, the LCORL gene was hypothesized to be associated with growth traits and hide weight in Dezhou donkeys. In this study, we aimed to reveal the variation of the LCORL gene in the Dezhou donkey and explore whether the gene is associated with hide weight and body size. In this study, genetic polymorphisms in the LCORL gene of the Dezhou donkey were studied using targeted sequencing technology, and single nucleotide polymorphisms (SNPs) of the LCORL gene were analyzed for association with hide weight and body size in Dezhou donkeys. The results showed that there was an SNP locus situated in intron 1 of the LCORL gene. Association analysis revealed that individuals with the GG genotype had significantly higher body height, body length, chest circumference and hide weight than those with the AA genotype (p < 0.05). Therefore, the g.112558859 A > G locus can be used as a potential candidate marker affecting body size and hide weight. This study provides the foundation for breeding high-quality donkeys with high hide yield.
| S-EPMC9559650 | biostudies-literature
Project description:The association of IGF-I gene polymorphisms with certain traits in 708 individuals of two Chinese dairy-goat breeds (Guanzhong and Xinong Saanen) was investigated. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods were employed in screening for genetic variation. Two novel mutations were detected in the 5'-flanking region and in intron 4 of IGF-I gene, viz., g.1617 G > A and g.5752 G > C (accession D26119.2), respectively. The associations of the g.1617 G > A mutation with milk yield and the body size were not significant (p > 0.05). However, in the case of g.5752 G > C, Xinong Saanen dairy goats with the CG genotype presented longer bodies (p < 0.05). Chest circumference (p < 0.05) was larger in Guanzhong goats with the GG genotype. In Xinong Saanen dairy goats with the CC genotype, milk yields were significantly higher during the first and second lactations (p < 0.05). Hence, the g.5752 G > C mutation could facilitate association analysis and serve as a genetic marker for Chinese dairy-goat breeding and genetics.
| S-EPMC3036871 | biostudies-literature
Project description:BACKGROUND:Truncating variants in the Titin gene (TTNtvs) are common in individuals with idiopathic dilated cardiomyopathy (DCM). However, a comprehensive genomics-first evaluation of the impact of TTNtvs in different clinical contexts, and the evaluation of modifiers such as genetic ancestry, has not been performed. METHODS:We reviewed whole exome sequence data for >71?000 individuals (61?040 from the Geisinger MyCode Community Health Initiative (2007 to present) and 10?273 from the PennMedicine BioBank (2013 to present) to identify anyone with TTNtvs. We further selected individuals with TTNtvs in exons highly expressed in the heart (proportion spliced in [PSI] >0.9). Using linked electronic health records, we evaluated associations of TTNtvs with diagnoses and quantitative echocardiographic measures, including subanalyses for individuals with and without DCM diagnoses. We also reviewed data from the Jackson Heart Study to validate specific analyses for individuals of African ancestry. RESULTS:Identified with a TTNtv in a highly expressed exon (hiPSI) were 1.2% individuals in PennMedicine BioBank and 0.6% at Geisinger. The presence of a hiPSI TTNtv was associated with increased odds of DCM in individuals of European ancestry (odds ratio [95% CI]: 18.7 [9.1-39.4] {PennMedicine BioBank} and 10.8 [7.0-16.0] {Geisinger}). hiPSI TTNtvs were not associated with DCM in individuals of African ancestry, despite a high DCM prevalence (odds ratio, 1.8 [0.2-13.7]; P=0.57). Among 244 individuals of European ancestry with DCM in PennMedicine BioBank, hiPSI TTNtv carriers had lower left ventricular ejection fraction (?=-12%, P=3×10-7), and increased left ventricular diameter (?=0.65 cm, P=9×10-3). In the Geisinger cohort, hiPSI TTNtv carriers without a cardiomyopathy diagnosis had more atrial fibrillation (odds ratio, 2.4 [1.6-3.6]) and heart failure (odds ratio, 3.8 [2.4-6.0]), and lower left ventricular ejection fraction (?=-3.4%, P=1×10-7). CONCLUSIONS:Individuals of European ancestry with hiPSI TTNtv have an abnormal cardiac phenotype characterized by lower left ventricular ejection fraction, irrespective of the clinical manifestation of cardiomyopathy. Associations with arrhythmias, including atrial fibrillation, were observed even when controlling for cardiomyopathy diagnosis. In contrast, no association between hiPSI TTNtvs and DCM was discerned among individuals of African ancestry. Given these findings, clinical identification of hiPSI TTNtv carriers may alter clinical management strategies.
| S-EPMC6602806 | biostudies-literature
Project description:Most birds sit on their eggs during incubation, a behaviour that likely evolved among non-avian dinosaurs. Several 'brooding' specimens of smaller species of oviraptorosaurs and troodontids reveal these non-avian theropods sat on their eggs, although little is known of incubation behaviour in larger theropod species. Here we examine egg clutches over a large body size range of oviraptorosaurs in order to understand the potential effect of body size on incubation behaviour. Eggshell porosity indicates that the eggs of all oviraptorosaurs were exposed in the nest, similar to brooding birds. Although all oviraptorosaur clutches consist of radially arranged eggs in a ring configuration, clutch morphology varies in that the central opening is small or absent in the smallest species, becomes significantly larger in larger species, and occupies most of the nest area in giant species. Our results suggest that the smallest oviraptorosaurs probably sat directly on the eggs, whereas with increasing body size more weight was likely carried by the central opening, reducing or eliminating the load on the eggs and still potentially allowing for some contact during incubation in giant species. This adaptation, not seen in birds, appears to remove the body size constraints of incubation behaviour in giant oviraptorosaurs.
| S-EPMC6012691 | biostudies-literature
Project description:The timing of associations between common genetic variants for weight or body mass index (BMI) across the life course may provide insights into the aetiology of obesity. We genotyped variants in FTO (rs9939609) and near MC4R (rs17782313) in 1240 men and 1239 women born in 1946 and participating in the MRC National Survey of Health and Development. Birth weight was recorded and height and weight were measured or self-reported repeatedly at 11 time-points between ages 2 and 53 years. Hierarchical mixed models were used to test whether genetic associations with weight or BMI standard deviation scores (SDS) changed with age during childhood and adolescence (2-20 years) or adulthood (20-53 years). The association between FTO rs9939609 and BMI SDS strengthened during childhood and adolescence (rate of change: 0.007 SDS/A-allele/year; 95% CI: 0.003-0.010, P < 0.001), reached a peak strength at age 20 years (0.13 SDS/A-allele, 0.08-0.19), and then weakened during adulthood (-0.003 SDS/A-allele/year, -0.005 to -0.001, P = 0.001). MC4R rs17782313 showed stronger associations with weight than BMI; its association with weight strengthened during childhood and adolescence (0.005 SDS/C-allele/year; 0.001-0.008, P = 0.006), peaked at age 20 years (0.13 SDS/C-allele, 0.07-0.18), and weakened during adulthood (-0.002 SDS/C-allele/year, -0.004 to 0.000, P = 0.05). In conclusion, genetic variants in FTO and MC4R showed similar biphasic changes in their associations with BMI and weight, respectively, strengthening during childhood up to age 20 years and then weakening with increasing adult age. Studies of the aetiology of obesity spanning different age groups may identify age-specific determinants of weight gain.
| S-EPMC2798720 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:As risk of hemorrhagic stroke may have early life origins, we investigated associations of birth weight and childhood body mass index (BMI) with adult intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH). METHODS:We included 240,234 Danish schoolchildren, born 1936 to 1989, with information on birth weight and measured weights and heights from 7 to 13 years. We calculated hazard ratios (HRs) and confidence intervals (CIs) for the associations between early life anthropometrics and ICH or SAH, identified through linkage with national registers. RESULTS:During the study period, 1,947 individuals (39% women) experienced an ICH and 797 individuals (64% women) experienced a SAH. Per 500 g increase in birth weight, women had a 10% decreased risk of SAH (HR, 0.90; 95% CI, 0.83 to 0.97) and men had a 10% decreased risk of ICH (HR, 0.90; 95% CI, 0.85 to 0.95). Birth weight was not associated with risks of ICH in women or SAH in men. In men, a childhood BMI below average (BMI z-score <0) was associated with increased risks of ICH. The association was stronger at older childhood ages, and at 13 years a BMI z-score of -1 was associated with a HR of 1.17 (95% CI, 1.06 to 1.28), and a BMI z-score of -2 with a HR of 1.46 (95% CI, 1.17 to 1.82) for ICH. Childhood BMI was not associated with risks of ICH in women or with risks of SAH in both sexes. CONCLUSION:s Early life body size is associated with ICH and SAH, and the associations differ by sex.
| S-EPMC6372895 | biostudies-other
Project description:Prolificacy of most local goat breeds in China is low. Jining Grey goat is one of the most prolific goat breeds in China, it is an important goat breed for the rural economy. ASMT (acetylserotonin O-methyltransferase) and ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif) are essential for animal reproduction. Single nucleotide polymorphisms (SNPs) of ASMT and ADAMTS1 genes in the highly prolific breed (Jining Grey goats), medium prolific breed (Boer goats and Guizhou White goats) and low prolific breeds (Angora goats, Liaoning Cashmere goats and Inner Mongolia Cashmere goats) were detected by polymerase chain reaction-restriction fragment length polymorphism and sequencing. Two SNPs (g.158122T>C, g.158700G>A) of ASMT gene and two SNPs (g.7979798A>G, g.7979477C>T) of ADAMTS1 gene were identified. For g.158122T>C of ASMT gene, further analysis revealed that genotype TC or CC had 0.66 (p < 0.05) or 0.75 (p < 0.05) kids more than those with genotype TT in Jining Grey goats. No significant difference (p > 0.05) was found in litter size between TC and CC genotypes. The SNP (g.158122T>C) caused a p.Tyr298His change and this SNP mutation resulted in changes in protein binding sites and macromolecule-binding sites. The improvement in reproductive performance may be due to changes in the structure of ASMT protein. For g.7979477C>T of ADAMTS1 gene, Jining Grey does with genotype CT or TT had 0.82 (p < 0.05) or 0.86 (p < 0.05) more kids than those with genotype CC. No significant difference (p > 0.05) was found in litter size between CT or TT genotypes. These results preliminarily indicated that C allele (g.158122T>C) of ASMT gene and T allele (g.7979477C>T) of ADAMTS1 gene are potential molecular markers which could improve litter size of Jining Grey goats and be used in goat breeding.
| S-EPMC7738733 | biostudies-literature
Project description:BackgroundPathogenic variants in single genes encoding podocyte-associated proteins have been implicated in about 30% of steroid-resistant nephrotic syndrome (SRNS) patients in children. However, LAMA5 gene biallelic variants have been identified in only seven patients so far, and most are missense variants of unknown significance. Furthermore, no functional analysis had been conducted for all but one of these variants. Here, we report three patients with LAMA5 gene biallelic truncating variants manifesting infantile nephrotic syndrome, and one patient with SRNS with biallelic LAMA5 missense variants.MethodsWe conducted comprehensive gene screening of Japanese patients with severe proteinuria. With the use of targeted next-generation sequencing, 62 podocyte-related genes were screened in 407 unrelated patients with proteinuria. For the newly discovered LAMA5 variants, we conducted in vitro heterotrimer formation assays.ResultsBiallelic truncating variants in the LAMA5 gene (NM_005560) were detected in three patients from two families. All patients presented with proteinuria within 6 months of age. Patients 1 and 2 were siblings possessing a nonsense variant (c.9232C>T, p.[Arg3078*]) and a splice site variant (c.1282 + 1G>A) that led to exon 9 skipping and a frameshift. Patient 3 had a remarkable irregular contour of the glomerular basement membrane. She was subsequently found to have a nonsense variant (c.8185C>T, p.[Arg2720*]) and the same splice site variant in patients 1 and 2. By in vitro heterotrimer formation assays, both truncating variants produced smaller laminin α5 proteins that nevertheless formed trimers with laminin β1 and γ1 chains. Patient 4 showed SRNS at the age of 8 years, and carried compound heterozygous missense variants (c.1493C>T, p.[Ala498Val] and c.8399G>A, p.[Arg2800His]).ConclusionsOur patients showed clear evidence of biallelic LAMA5 truncating variants causing infantile nephrotic syndrome. We also discerned the clinical and pathologic characteristics observed in LAMA5-related nephropathy. LAMA5 variant screening should be performed in patients with congenital/infantile nephrotic syndrome.
| S-EPMC8986055 | biostudies-literature