Allelic Interactions Research Articles

Clinical associations and genetic interactions of oncogenic BRAF alleles.

BRAF is a serine/threonine-specific protein kinase that regulates the MAPK/ERK signaling pathway, and mutations in the BRAF gene are considered oncogenic drivers in diverse types of cancer. Based on the signaling mechanism, oncogenic BRAF mutations can be assigned to three different classes: class 1 mutations constitutively activate the kinase domain and lead to RAS-independent signaling, class 2 mutations induce artificial dimerization of BRAF and RAS-independent signaling and class 3 mutations display reduced or abolished kinase function and require upstream signals.Despite the importance of BRAF mutations in cancer, the clinical associations, genetic interactions and therapeutic implications of non-V600 BRAF mutations have not been explored comprehensively yet. In this study, the author analyzed publically available data from the AACR Project GENIE to further understand clinical associations and genetic interactions of oncogenic BRAF mutations. The analyses identified 93 recurrent BRAF mutations, out of which 50 could be assigned to a functional class based on literature review. The author could show that the frequency of BRAF mutations varies across cancer types and subtypes, and that the BRAF mutation classes are unequally distributed across cancer types and subtypes. Using permutation testing-based co-occurrence analyses, the author defined the genetic interactions of BRAF mutations in multiple cancer types and revealed unexplored genetic interactions that might define clinically relevant subgroups. With non-small cell lung cancer as example, the author further showed that the genetic interactions are BRAF mutation class-specific. The presented analyses explore the properties of oncogenic BRAF mutations and will help to further delineate the complex role of BRAF in cancer.

Case-only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD-2353F22.1 implying the importance of periodontal wound healing for disease aetiology.

The basis of phenotypic variation of periodontitis is genetic variability. Disease relevant effects of individual risk alleles are considered to result from genetic interactions. We investigated gene × gene (G×G) interactions of suggestive periodontitis susceptibility alleles. We used the case-only design and investigated single-nucleotide polymorphism (SNPs) that showed associations in our recent genome-wide association study (GWAS) and GWAS meta-analysis with p < 5 × 10-6 . CRISPR-dCas9 gene activation followed by RNA-sequencing and gene-set enrichment analyses elucidated differentially expressed genes and gene networks. With the databases of SNPInspector and Transfac professional, luciferase reporter gene assays and antibody electrophoretic mobility shift experiments, we analysed allele-specific effects on transcription factor binding. SNPs at the genes sialic acid binding Ig-like lectin 5 (SIGLEC5) and plasminogen (PLG) showed G×G interactions with rs1122900 at the long non-coding RNA (lncRNA) CTD-2353F22. Associated chromatin cis-activated CTD-2353F22.1 6.5-fold (p=.003), indicating CTD-2353F22.1 as target gene of this interaction. CTD-2353F22.1 regulated GADD45A (padj < 4.9 × 10-11 , log2 fold change (FC)=-0.55), THBS1, SERPINE1 and Tissue Factor F3 (padj < 5 × 10-7 , log2 FC ≥ -0.35) and the gene set "angiogenesis" (area under the curve=0.71, padj =8.2 × 10-5 ). rs1122900 effect C-allele decreased reporter gene activity (5.5-fold, p=.0003) and PRDM14 binding (76%). CTD-2353F22.1 mediates interaction of SIGLEC5 and PLG, together with genes that function in periodontal wound healing.

Mapping of QTLs controlling barley agronomic traits (Hordeum vulgare L.) under normal conditions and drought and salinity stress at reproductive stage

The present study is focused on mapping the genomic regions for controlling some agronomic traits in the reproductive stage of barley under normal, drought and saline conditions. In this regard, a total of 103 samples of F8 families derived from the cross of two cultivars of Badia×Kavir were planted in a completely randomized design in the crop year 2018–2019. The research procedure has been accomplished in the greenhouse of Gonbad Kavous University in three replications. In this case, transgressive segregation was observed for the evaluated traits. This situation indicated the difference between allelic interactions in the parents. Also, linkage maps were prepared using 152 SSR polymorphic markers, 72 ISSR alleles, 7 IRAP alleles, 29 CAAT alleles, 27 SCoT alleles, and 15 iPBS alleles. These markers were assigned to the seven barley chromosomes. Thus, the obtained map covered 999.29 centiMorgans (cM) of the barley genome length, and the average distance between two flanking markers was 3.387 cM. In this study, the most significant QTL under normal conditions have been identified on chromosomes 1, 5, and 6. In the drought conditions, four major QTLs were detected for spike diameter, awn weight, flag leaf weight (qPPT-7, qAWW-7, qFLW-4a and qFLW-5). Under salinity stress conditions, two major QTLs were identified for the number of leaves qLEN-6a and shoot diameter qSHT-6b. In this case, the values of R2 were 18.3 and 17.6, respectively. The major QTLs that control the effect of the desired traits and the markers associated with them can be used in marker-assisted selection programs.

Associations between cognitive function and endogenous levels of estradiol and testosterone in adults with type 2 diabetes

AimsTo assess associations that endogenous estradiol and testosterone levels have with cognitive function in older adults with Type 2 diabetes mellitus (T2DM). MethodsWe use data from the Look AHEAD clinical trial of behavioral weight loss. Endogenous estradiol and total testosterone levels were determined using stored serum from 996 individuals, mean age 69 years, at two times (averaging 4 years apart) during years 8–18 of follow-up. One to four standardized assessments of attention, executive function, memory, and verbal fluency were collected during this follow-up. Mixed effects models and multiple imputation were used to assess associations that estradiol and total testosterone levels had with body mass index and cognitive function. ResultsEstradiol levels were not associated with cognitive function in either sex. Total testosterone levels were not associated with cognitive function in women, but greater total testosterone levels were associated with better verbal fluency in men (p < 0.001), most strongly among those carrying the APOE-e4 allele (interaction p = 0.02). The weight loss intervention left a legacy of relatively lower cognitive functioning among women, which was not mediated by current levels of sex hormones. ConclusionsBehavioral weight loss intervention does not affect cognitive functioning through mechanisms related to estradiol or testosterone.ClinicalTrials.gov Identifier: NCT00017953.

Multi-locus genome-wide association studies reveal novel alleles for flowering time under vernalisation and extended photoperiod in a barley MAGIC population

Key messageKey genes controlling flowering and interactions of different photoperiod alleles with various environments were identified in a barley MAGIC population. A new candidate gene for vernalisation requirements was also detected.Optimal flowering time has a major impact on grain yield in crop species, including the globally important temperate cereal crop barley (Hordeum vulgare L.). Understanding the genetics of flowering is a key avenue to enhancing yield potential. Although bi-parental populations were used intensively to map genes controlling flowering, their lack of genetic diversity requires additional work to obtain desired gene combinations in the selected lines, especially when the two parental cultivars did not carry the genes. Multi-parent mapping populations, which use a combination of four or eight parental cultivars, have higher genetic and phenotypic diversity and can provide novel genetic combinations that cannot be achieved using bi-parental populations. This study uses a Multi-parent advanced generation intercross (MAGIC) population from four commercial barley cultivars to identify genes controlling flowering time in different environmental conditions. Genome-wide association studies (GWAS) were performed using 5,112 high-quality markers from Diversity Arrays Technology sequencing (DArT-seq), and Kompetitive allele-specific polymerase chain reaction (KASP) genetic markers were developed. Phenotypic data were collected from fifteen different field trials for three consecutive years. Planting was conducted at various sowing times, and plants were grown with/without additional vernalisation and extended photoperiod treatments. This study detected fourteen stable regions associated with flowering time across multiple environments. GWAS combined with pangenome data highlighted the role of CEN gene in flowering and enabled the prediction of different CEN alleles from parental lines. As the founder lines of the multi-parental population are elite germplasm, the favourable alleles identified in this study are directly relevant to breeding, increasing the efficiency of subsequent breeding strategies and offering better grain yield and adaptation to growing conditions.

Interchromosomal interaction of homologous Stat92E alleles regulates transcriptional switch during stem-cell differentiation

Pairing of homologous chromosomes in somatic cells provides the opportunity of interchromosomal interaction between homologous gene regions. In the Drosophila male germline, the Stat92E gene is highly expressed in a germline stem cell (GSC) and gradually downregulated during the differentiation. Here we show that the pairing of Stat92E is always tight in GSCs and immediately loosened in differentiating daughter cells, gonialblasts (GBs). Disturbance of Stat92E pairing by relocation of one locus to another chromosome or by knockdown of global pairing/anti-pairing factors both result in a failure of Stat92E downregulation, suggesting that the pairing is required for the decline in transcription. Furthermore, the Stat92E enhancer, but not its transcription, is required for the change in pairing state, indicating that pairing is not a consequence of transcriptional changes. Finally, we show that the change in Stat92E pairing is dependent on asymmetric histone inheritance during the asymmetric division of GSCs. Taken together, we propose that the changes in Stat92E pairing status is an intrinsically programmed mechanism for enabling prompt cell fate switch during the differentiation of stem cells.

Dyslipidaemia-Genotype Interactions with Nutrient Intake and Cerebro-Cardiovascular Disease.

A comprehensive understanding of gene-diet interactions is necessary to establish proper dietary guidelines to prevent and manage cardio-cerebrovascular disease (CCD). We investigated the role of genetic variants associated with dyslipidaemia (DL) and their interactions with macro-nutrients for cardiovascular disease using a large-scale genome-wide association study of Korean adults. A total of 58,701 participants from a Korean genome and epidemiology study were included. Their dietary intake was assessed using a food frequency questionnaire. Dyslipidaemia was defined as total cholesterol (TCHL) ≥ 240 mg/dL, high-density lipoprotein (HDL) < 40 mg/dL, low-density lipoprotein (LDL) ≥ 160 mg/dL, triglycerides (TG) ≥ 200 mg/dL, or dyslipidaemia history. Their nutrient intake was classified as follows: protein intake: high ≥ 30%, 30% > moderate ≥ 20%, and 20% > low in daily total energy intake (TEI); carbohydrate intake: high ≥ 60%, 60% > moderate ≥ 50%, and 50% > low; fat intake: high ≥ 40%, 40% > moderate ≥ 30%, and 30% > low. Odds ratios and 95% confidence intervals were calculated after adjusting for age; sex; body mass index (BMI); exercise status; smoking status; alcohol intake; principal component 1 (PC1); principal component 2 (PC2); and intake of carbohydrates, fats, and proteins. This analysis included 20,596 patients with dyslipidaemia and 1027 CCD patients. We found that rs2070895 related to LIPC was associated with HDL-cholesterol. Patients with the minor allele (A) in rs2070895 had a lower risk of CCD than those carrying the reference allele (G) (odds ratio [OR] = 0.8956, p-value = 1.78 × 10−2). Furthermore, individuals consuming protein below 20% TEI with the LIPC reference allele had a higher risk of CCD than those with the minor allele (interaction p-value 6.12 × 10−3). Our findings suggest that the interactions of specific polymorphisms associated with dyslipidaemia and nutrients intake can influence CCD.

MO044: Cellular mechanism of the exceptional dominant transmission in NPHS2-associated glomerulopathy

Abstract BACKGROUND AND AIMS Mutations of NPHS2 cause autosomal recessive steroid-resistant nephrotic syndrome (SRNS). The encoded podocin, a key component of the slit diaphragm, homo-oligomerizes through two C-terminal oligomerization sites. We formerly found that specific podocin variants may exert a dominant negative effect against R229Q podocin variant secondary to an altered oligomerization [1, 2]. Recently, two families with autosomal dominant focal segmental glomerulosclerosis were found to carry a de novo heterozygous NPHS2 last-exon frameshift mutations affecting the second oligomerization site (either c.989_992delTGTC, p.L330Pfs*17 or c.988_989delCT, p.L330Vfs*15) [3]. We hypothesized that these podocin variants exert a dominant negative effect against wild type (WT) podocin. METHODS We coexpressed eGFP-tagged WT podocin with either hemagglutinin-tagged (HA) WT, p.L330Pfs*17 or p.L330Vfs*15 podocin variants in cultured podocytes. Plasma membrane was stained with CF405M-conjugated wheat germ agglutinin (WGA), and immunohistochemical staining was performed with primary anti-HA and secondary AlexaFluor568-conjugated antibodies. All analysis was done in a blinded fashion. The membrane-targeting of podocin was assessed by the ratio of the WGA-labeled perimembranous area that colocalized with podocin (Mander's overlap coefficients, MOC) and the colocalization of the coexpressed variants were estimated as Pearson correlation coefficients (PCC) by FiJi software on confocal microscopic images. MOC and PCC were compared by Holmes–Bonferroni adjusted Wilcoxon signed-rank test. RESULTS The frameshift podocin variants were not membranous in monoexpression [MOC: HA-p.L330Pfs*17 (n = 26): 0.08 (0.03–0.22) median (interquartile ranges); HA-p.L330Vfs*15 (n = 24): 0.07 (0.02–0.16)]. The GFP-tagged WT podocin strongly colocalized with the HA-tagged WT or frameshift podocin variants [PCC: WT-eGFP + HA-WT (n = 19): 0.64 (0.49–0.71); WT-eGFP + HA-L330Pfs*17 (n = 17): 0.54 (0.35–0.58); WT-eGFP + HA-L330Vfs*15 (n = 17): 0.44 (0.29–0.66)]. The GFP-WT podocin was retained in intracellular compartments in the presence of any of the two frameshift podocin variants [MOCWT(WT) = 0.58 (0.46–0.69)], MOCWT(L330Pfs*17) = 0.01 (0.002–0.029), P = 2x10-6 versus WT(WT); MOCWT(L330Vfs*15) = 0.003 (0.001–0.013), P = 2 x 10−6 versus WT(WT)]. CONCLUSIONS The dominant podocin variants retain WT podocin in intracellular compartments explaining the exceptional dominant transmission of NPHS2-associated glomerulopathy. This is in accordance with our former results showing the primary role of C-terminal hetero-oligomerization in exerting interallelic interactions of NPHS2 alleles. FUNDING MTA-SE Lendulet Research Grant (LP2015-11/2015), OTKA KH125566 and K135798, and ÚNKP-20–3-I-SE-29 from the source of the National Research, Development and Innovation Fund.

Genetic Control of Reproductive Traits under Different Temperature Regimes in Inbred Line Populations Derived from Crosses between S. pimpinellifolium and S. lycopersicum Accessions.

In the present work, we study the genetic control of reproductive traits under different heat stress conditions in two populations of inbred lines derived from crosses between two S. pimpinellifolium accessions and two tomato cultivars (E9×L5 and E6203×LA1589). The temperature increase affected the reproductive traits, especially at extremely high temperatures, where only a few lines were able to set fruits. Even though a relative modest number of QTLs was identified, two clusters of QTLs involved in the responses of reproductive traits to heat stress were detected in both populations on chromosomes 1 and 2. Interestingly, several epistatic interactions were detected in the E9×L5 population, which were classified into three classes based on the allelic interaction: dominant (one locus suppressed the allelic effects of a second locus), co-adaptive (the double-homozygous alleles from the same parent alleles showed a higher phenotypic value than the combination of homozygous alleles from alternative parents) and transgressive (the combination of double-homozygous alleles from different parents showed better performance than double-homozygous alleles from the same parents). These results reinforce the important role of non-additive genetic variance in the response to heat stress and the potential of the new allelic combinations that arise after wide crosses.

SNPs of FOXO1 and Their Interactions Contributes to the Enhanced Risk of Diabetes Among Elderly Individuals.

We have assessed the impact of three single nucleotide polymorphisms (SNPs) of Forkhead Box O1 (FOXO1) and their interaction on susceptibility of type 2 diabetes mellitus in geriatric population from northern India. We genotyped three SNPs (rs2721068, rs17446614, and rs4581585) of FOXO1 gene in 190 elderly individuals with diabetes and 182 unrelated healthy controls of similar ethnicity by using TaqMan SNP assays. SNP-SNP and SNP-environment interactions among polymorphic loci were studied by the multifactor dimensionality reduction (MDR) method. The AA genotype carriers of rs17446614 was associated with the increased susceptibility of diabetes in both adjusted and unadjusted model, whereas rs4581585 was associated with the risk in unadjusted model only. Genotype and minor allele interaction with quantitative parameters revealed that AA genotype of rs17446614 had significantly higher fasting plasma glucose (FPG) in diabetic subjects, also minor allele (A) in patients was positively associated with FPG and glycated hemoglobin. Haplotype Trs2721068Grs17446614Trs4581585 increases the risk of diabetes, whereas carrier of haplotypes Crs2721068Grs17446614Crs4581585 and Crs2721068 Grs17446614Trs4581585 were protective. The MDR analysis revealed that interaction of rs17446614 with body mass index (BMI) increased the susceptibility of diabetes. Therefore presence of rs17446614 variant and its interaction with BMI and haplotype Trs2721068Grs17446614Trs4581585 modulates the risk of diabetes and can be used as a promising tool for identifying high-risk individuals.

Features of the heterosis manifestation in monoecious hybrids of cannabis-free hemp and their resistance to adverse environmental conditions

The article deals with the manifestation of heterosis by economically valuable traits in monoecious hybrids of hashishfree monoecious hemp. Heterosis is one of the reserves for increasing yields and improving the quality of hemp products. In terms of seed harvest, the vast majority of combinations exceed parental varieties. The highest outbreak of heterosis was obtained by crossing varieties Glukhovskaya-10 and YSO-1. In relation to the most productive parent, the degree of heterosis reaches 38.5%. An increase in seed harvest is a derivative of the heterosis of several components: the weight of the plant, the length of the inflorescence, the weight of seeds per plant, the weight of 1000 seeds and the number of seeds per plant. Of these, the most important are the weight of seeds per plant and the weight of 1000 seeds. According to the harvest of straw and fiber, the manifestation of heterosis is limited. Most hybrids have indicators equal to those of the best parental varieties. However, these hybrids significantly exceed the best monoecious variety YSO-1 recommended for cultivation, which is of practical interest. Hybrid plants are more resistant to adverse conditions than the parent varieties. Homeostasis of hybrids depends on the degree of heterozygosity of the organism, as well as the nature of the interaction of alleles of heterozygous loci. The results of our research show that it is possible to consciously control the process of obtaining highly productive hybrid seeds, spending a small amount of labor and funds for its implementation.

LRFN5 locus structure is associated with autism and influenced by the sex of the individual and locus conversions.

LRFN5 is a regulator of synaptic development and the only gene in a 5.4 Mb mammalian‐specific conserved topologically associating domain (TAD); the LRFN5 locus. An association between locus structural changes and developmental delay (DD) and/or autism was suggested by several cases in DECIPHER and own records. More significantly, we found that maternal inheritance of a specific LRFN5 locus haplotype segregated with an identical type of autism in distantly related males. This autism‐susceptibility haplotype had a specific TAD pattern. We also found a male/female quantitative difference in the amount histone‐3‐lysine‐9‐associated chromatin around the LRFN5 gene itself (p < 0.01), possibly related to the male‐restricted autism susceptibility. To better understand locus behavior, the prevalence of a 60 kb deletion polymorphism was investigated. Surprisingly, in three cohorts of individuals with DD (n = 8757), the number of deletion heterozygotes was 20%–26% lower than expected from Hardy–Weinberg equilibrium. This suggests allelic interaction, also because the conversions from heterozygosity to wild‐type or deletion homozygosity were of equal magnitudes. Remarkably, in a control group of medical students (n = 1416), such conversions were three times more common (p = 0.00001), suggesting a regulatory role of this allelic interaction. Taken together, LRFN5 regulation appears unusually complex, and LRFN5 dysregulation could be an epigenetic cause of autism.Lay SummaryLRFN5 is involved with communication between brain cells. The gene sits alone in a huge genomic niche, called the LRFN5 locus, of complex structure and high mammalian conservation. We have found that a specific locus structure increases autism susceptibility in males, but we do not yet know how common this epigenetic cause of autism is. It is, however, a cause that potentially could explain why higher‐functioning autism is more common in males than females.

Repeated origins, widespread gene flow, and allelic interactions of target-site herbicide resistance mutations.

Causal mutations and their frequency in agricultural fields are well-characterized for herbicide resistance. However, we still lack understanding of their evolutionary history: the extent of parallelism in the origins of target-site resistance (TSR), how long these mutations persist, how quickly they spread, and allelic interactions that mediate their selective advantage. We addressed these questions with genomic data from 19 agricultural populations of common waterhemp (Amaranthus tuberculatus), which we show to have undergone a massive expansion over the past century, with a contemporary effective population size estimate of 8 x 107. We found variation at seven characterized TSR loci, two of which had multiple amino acid substitutions, and three of which were common. These three common resistance variants show extreme parallelism in their mutational origins, with gene flow having shaped their distribution across the landscape. Allele age estimates supported a strong role of adaptation from de novo mutations, with a median age of 30 suggesting that most resistance alleles arose soon after the onset of herbicide use. However, resistant lineages varied in both their age and evidence for selection over two different timescales, implying considerable heterogeneity in the forces that govern their persistence. Two such forces are intra- and inter-locus allelic interactions; we report a signal of extended haplotype competition between two common TSR alleles, and extreme linkage with genome-wide alleles with known functions in resistance adaptation. Together, this work reveals a remarkable example of spatial parallel evolution in a metapopulation, with important implications for the management of herbicide resistance.

NAFLD-related gene polymorphisms and all-cause and cause-specific mortality in an Asian population: the Shanghai Changfeng Study.

The PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile. To investigate the effects of the NAFLD risk alleles on the all-cause and cause-specific mortality in 5581 Chinese adults. The genome-wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data. Genome-wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 C>G variant (P=8.6×10-7 ). Further analyses validated the associations of TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants with NAFLD. During 29425.1 person-years of follow-up, the overall mortality was 816 per 100000 person-years, where 299 deaths were attributable to cardiovascular disease and 85 to liver disease. The PNPLA3 rs738409 C>G variant was independently associated with increased liver-specific mortality (P for trend=0.034) but reduced cardiovascular mortality (P for trend=0.047). A composite genetic-predisposition score of PNPLA3, TM6SF2, and MBOAT7 risk alleles presented similar opposite effects on liver-specific and cardiovascular mortality. Moreover, interactions of the NAFLD risk alleles with adiposity for liver-specific mortality were found (Pinteraction <0.05). The reduced serum VLDL1 concentration was responsible for the increased liver-specific mortality related to NAFLD risk alleles. The PNPLA3 rs738409 C>G variant and its combination with TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants increase liver-specific mortality but reduce cardiovascular mortality in overweight/obese Chinese.

Partial Results Regarding the Genetic Determinism of Growth Process in a Native Horse Breed using Wither’s Height

Study of variability in domestic animal populations is the foundation of quantitative genetics. Based on statistical methods, the weights of the total phenotype variation that belong to its different fractions (causal components) are quantified: variation due to gene additive effect, variation due to allelic and non-allelic interactions, variation due to environment (general and special), variation due to genotype-environment interaction and possibly variation due to the association between genotype and environment. In this study, during 2017-2020, we used the method of analysis of variance with two sources of variation. The material was represented by 538 individuals from Hucul horse breed analyzed at 18, 30 and 42 months old). The heritability of character was 0.3402±0.1546 (18 months), 0.5549±0.2225 (30 months), 0.4506±0.1895 (42 months), suggest that this is a hereditary condition that follows a quantitative model of inheritance, where the influence of additive genetic factors is moderate to intense. We can conclude that, in this native breed and for this character, a significant share of the phenotypic value is due to the additive effect of genes.

Tracing the Origin of the RSPO2 Long-Hair Allele and Epistatic Interaction between FGF5 and RSPO2 in Sapsaree Dog.

Genetic analysis of the hair-length of Sapsaree dogs, a Korean native dog breed, showed a dominant mode of inheritance for long hair. Genome-Wide Association Study (GWAS) analysis and subsequent Mendelian segregation analysis revealed an association between OXR1, RSPO2, and PKHD1L1 on chromosome 13 (CFA13). We identified the previously reported 167 bp insertion in RSPO2 3’ untranslated region as a causative mutation for hair length variations. The analysis of 118 dog breeds and wolves revealed the selection signature on CFA13 in long-haired breeds. Haplotype analysis showed the association of only a few specific haplotypes to the breeds carrying the 167 bp insertion. The genetic diversity in the neighboring region linked to the insertion was higher in Sapsarees than in other Asian and European dog breeds carrying the same variation, suggesting an older history of its insertion in the Sapsaree genome than in that of the other breeds analyzed in this study. Our results show that the RSPO2 3’ UTR insertion is responsible for not only the furnishing phenotype but also determining the hair length of the entire body depending on the genetic background, suggesting an epistatic interaction between FGF5 and RSPO2 influencing the hair-length phenotype in dogs.

Genetic parameters controlling the inheritance of glaucousness and yield traits in bread wheat.

Wheat breeders frequently use generation mean analysis to obtain information on the type of gene action involved in inheriting a trait to choose the helpful breeding procedure for trait improvement. The present study was carried out to study the inter-allelic and intra-allelic gene action and inheritance of glaucousness, earliness and yield traits in a bread wheat cross between divergent parents in glaucousness and yield traits; namely Mut-2 (P1) and Sakha 93 (P2). The experimental material included six populations, i.e. P1, P2, F1, F2, BC1, and BC2 for this wheat cross. A randomized complete block design with three replications was used, and a six parameters model was applied. Additive effects were generally more critical than dominance for all studied traits, except for plant height (PH) and grain yield/plant (GYPP). The duplicate epistasis was observed in spike length; SL, spikes/plant; SPP and days to heading; DTH. All six types of allelic and non-allelic interaction effects controlled SL, GYPP, DTH and glaucousness. All three types of epistasis, i.e. additive x additive, additive x dominance, and dominance x dominance, are essential in determining the inheritance of four traits (SL, GYPP, DTH and glaucousness). Dominance × dominance effects were higher in magnitude than additive × dominance and additive × additive in most traits. The average degree of dominance was minor than unity in six traits (glaucousness, grains/spike, spike weight, days to maturity, 100-grain weight and SL), indicating partial dominance and selection for these traits might be more effective in early generations. Meanwhile, the remaining traits (PH, SPP, GYPP and DTH) had a degree of dominance more than unity, indicating that overdominance gene effects control such traits and it is preferable to postpone selection to later generations. The highest values of narrow-sense heritability and genetic advance were recorded by glaucousness trait followed by SL and SPP, indicating that selection in segregating generations would be more effective than other traits.

Genotype-phenotype correlation in phenylketonuria

Introduction. Phenylketonuria is an inborn metabolism error with a high phenotypical variability, due in part to the large number of implicated genetical variants (over 1200 reported) but also due to other factors. Establishing a genotype=phenotype correlation, accessible today through molecular testing, is an important instrument for diagnostical accuracy, personalized therapy, better evaluation of the prognostic and an optimal genetical advice. Objective. The article aims to make an analyze of the most recent progress made in the effort of increasing the predictive value of genotyping in establishing the evolution and the severity of the disease. Material and method. For this review there were analyzed article from specialty journals indexed to Pubmed database, published mainly in the last 10 years. Results. Genotype-phenotype correlations can be established in most patients, but in approximative 10% of cases there are discordances between previously reported data and the result found in some studies. This mismatch results from the allelic interaction in compound heterozygous, not yet fully understood, from the existence of variants with unpredictable evolution and from other, non-genetical factors. Conclusions. The genotype-phenotype relationship is increasingly better understood. Molecular testing in phenylketonuria and phenotypical predictions based on the genotype, obtained by comparison with international databases, have clinical importance for the genetic advice given to the family and for the therapeutic decision, among other reasons.

Genetic analysis of hair-length phenotype of Sapsaree dogs— tracing the origin of the RSPO2 long hair allele and epistatic interaction between FGF5 and RSPO2

Genetic analysis of hair-length phenotype of Sapsaree dogs— tracing the origin of the RSPO2 long hair allele and epistatic interaction between FGF5 and RSPO2

Genetic analysis of hair-length phenotype of Sapsaree dogs— tracing the origin of the RSPO2 long hair allele and epistatic interaction between FGF5 and RSPO2

Genetic analysis of hair-length phenotype of Sapsaree dogs— tracing the origin of the RSPO2 long hair allele and epistatic interaction between FGF5 and RSPO2