Combining ability status of the inbred lines is crucial information for hybrid breeding program. Diallel or line × tester mating designs are frequently used to evaluate the combining ability. In the current study a modified diallel model was used, wherein the Griffing\'s combining ability effects were further partitioned to understand the effects due to maternal and reciprocal. To do this, eight parental lines of maize were crossed in full diallel method and the generated hybrids along with parents were phenotyped. The field data on the quantitative traits was analyzed using both Griffing\'s and the modified model to determine how well the parents\' and the F1 hybrids combined. For each of the traits, a sizable reciprocal and maternal variance was observed. The number of kernel rows per cob variable had a ratio of additive variance to dominance variance greater than one. All other traits including grain yield had a ratio close to zero, suggesting that non-additive gene action was primarily responsible for the genetic control of most of the traits. The narrow sense heritability was low to moderate for majority of the variables, except for number of kernel rows per cob. With the help of the improved model, it was possible to choose superior parents and cross-parent pairings with accuracy. Based on the modified general combining ability effects and maternal effects, the parental line P5 was recognized as a potential female parent and P7 as a good male parent for grain yield and yield-attributing characteristics. The cross combination of P8×P1 had the highest specific combining ability effect on grain yield. P5×P6 cross had the highest reciprocal effect. The correlation analysis implies that the Griffing\'s general combining ability effects and specific combining ability effects were found to be less efficient in predicting F1 performance as compared to the modified model.

Body weight is an important economic trait for sheep meat production, and its genetic improvement is considered one of the main goals in the sheep breeding program. Identifying genomic regions that are associated with growth-related traits accelerates the process of animal breeding through marker-assisted selection, which leads to increased response to selection. In this study, we conducted a weighted single-step genome-wide association study (WssGWAS) to identify potential candidate genes for direct and maternal genetic effects associated with birth weight (BW) and weaning weight (WW) in Baluchi sheep. The data used in this research included 13,408 birth and 13,170 weaning records collected at Abbas-Abad Baluchi Sheep Breeding Station, Mashhad-Iran. Genotypic data of 94 lambs genotyped by Illumina 50K SNP BeadChip for 54,241 markers were used. The proportion of variance explained by genomic windows was calculated by summing the variance of SNPs within 1 megabase (Mb). The top 10 window genomic regions explaining the highest percentages of additive and maternal genetic variances were selected as candidate window genomic regions associated with body weights. Our findings showed that for BW, the top-ranked genomic regions (1 Mb windows) explained 4.30 and 4.92% of the direct additive and maternal genetic variances, respectively. The direct additive genetic variance explained by the genomic window regions varied from 0.31 on chromosome 1 to 0.59 on chromosome 8. The highest (0.84%) and lowest (0.32%) maternal genetic variances were explained by genomic windows on chromosome 10 and 17, respectively. For WW, the top 10 genomic regions explained 6.38 and 5.76% of the direct additive and maternal genetic variances, respectively. The highest and lowest contribution of direct additive genetic variances were 1.37% and 0.42%, respectively, both explained by genomic regions on chromosome 2. For maternal effects on WW, the highest (1.38%) and lowest (0.41%) genetic variances were explained by genomic windows on chromosome 2. Further investigation of these regions identified several possible candidate genes associated with body weight. Gene ontology analysis using the DAVID database identified several functional terms, such as translation repressor activity, nucleic acid binding, dehydroascorbic acid transporter activity, growth factor activity and SH2 domain binding.

ALS is a heterogeneous disease in which different factors such as mitochondrial phenotypes act in combination with a genetic predisposition. This study addresses the question of whether homoplasmic (total mitochondrial genome of a sample is affected) and/or heteroplasmic mutations (wildtype and mutant mitochondrial DNA molecules coexist) might play a role in familial ALS. Blood was drawn from familial ALS patients with a possible maternal pattern of inheritance according to their pedigrees, which was compared to blood of ALS patients without maternal association as well as age-matched controls. In two cohorts, we analyzed the mitochondrial genome from whole blood or isolated white blood cells and platelets using a resequencing microarray (Affymetrix MitoChip v2.0) that is able to detect homoplasmic and heteroplasmic mitochondrial DNA mutations and allows the assessment of low-level heteroplasmy.
We identified an increase in homoplasmic ND5 mutations, a subunit of respiratory chain complex I, in whole blood of ALS patients that allowed maternal inheritance. This effect was more pronounced in patients with bulbar onset. Heteroplasmic mutations were significantly increased in different mitochondrial genes in platelets of patients with possible maternal inheritance. No increase of low-level heteroplasmy was found in maternal ALS patients.
Our results indicate a contribution of homoplasmic ND5 mutations to maternally associated ALS with bulbar onset. Therefore, it might be conceivable that specific maternally transmitted rather than randomly acquired mitochondrial DNA mutations might contribute to the disease process. This stands in contrast with observations from Alzheimer\'s and Parkinson\'s diseases showing an age-dependent accumulation of unspecific mutations in mitochondrial DNA.

Minimizing bird mortality in the commercial quail breeding industry is important from an economic and welfare perspective. Genetic and non-genetic factors can influence on the cumulative survival of the birds (CS). Accordingly, this study aimed to investigate non-genetic factors on CSs (cumulative survival of the birds from hatch to 5 (CS1), 10 (CS2), 15 (CS3), 20 (CS4), 25 (CS5), 30 (CS6), 35 (CS7), 40 (CS8), and 45 (CS9) days of age), and estimation of the genetic parameters for CSs in crossbred population of quail. Data set included 1794 records from crossbred chicks hatched from 70 sires and 72 dams. The fixed effects were analyzed using an animal model by ASReml software, and all traits were analyzed using Bayesian method via Gibbs sampling by fitting of 6 threshold animal models including the direct genetic effect, the maternal permanent environmental effect, and the maternal genetic effect. The best fitted model for each trait was selected based on the deviance information criteria. Hatch number, the month of hatch, and combination of chickens showed a significant effect on CSs, but the sex of chickens does not have a significant effect on CSs. However, females have higher survival than males (except for CS1). With the best model, the highest and lowest direct heritability was estimated for CS5 (0.386) and CS3 (0.250), respectively. The maternal genetic effect was significant for CS1, CS2, CS3, and CS4 traits, but the maternal permanent environmental effect was significant only for CS1. The range of maternal heritability for CS1 to CS4 traits was estimated from 0.064 to 0.111, and ratio of the permanent environmental variance to phenotypic variance for CS1 was 0.021. The result showed that increasing of the birds\' survival could be performed by correcting non-genetic factors and genetic selection for CSs considering the maternal genetic effects in younger ages. HIGHLIGHTS: • In the commercial quail breeding industry, the bird mortality is important from an economic and welfare perspective. • Improving quail survival can be achieved by controlling the genetic and non-genetic factors affecting on survival, so knowledge of these factors is necessary. • The combination of crossbred chickens had a significant effect on cumulative survival traits. • The Cumulative survival traits in the crossbred population had relatively high genetic diversity, so genetic selection for these traits could be effective.

BACKGROUND: Efficient breeding programs are difficult to implement in honeybees due to their biological specificities (polyandry and haplo-diploidy) and complexity of the traits of interest, with performances being measured at the colony scale and resulting from the joint effects of tens of thousands of workers (called direct effects) and of the queen (called maternal effects). We implemented a Monte Carlo simulation program of a breeding plan designed specifically for Apis mellifera\'s populations to assess the impact of polyandry versus monoandry on colony performance, inbreeding level and genetic gain depending on the individual selection strategy considered, i.e. complete mass selection or within-family (maternal lines) selection. We simulated several scenarios with different parameter setups by varying initial genetic variances and correlations between direct and maternal effects, the selection strategy and the polyandry level. Selection was performed on colony phenotypes.
RESULTS: All scenarios showed strong increases in direct breeding values of queens after 20 years of selection. Monoandry led to significantly higher direct than maternal genetic gains, especially when a negative correlation between direct and maternal effects was simulated. However, the relative increase in these genetic gains depended also on their initial genetic variability and on the selection strategy. When polyandry was simulated, the results were very similar with either 8 or 16 drones mated to each queen. Across scenarios, polyandrous mating resulted in equivalent or higher gains in performance than monoandrous mating, but with considerably lower inbreeding rates. Mass selection conferred a ~ 20% increase in performance compared to within-family selection, but was also accompanied by a strong increase in inbreeding levels (25 to 50% higher).
CONCLUSIONS: Our study is the first to compare the long-term effects of polyandrous versus monoandrous mating in honeybee breeding. The latter is an emergent strategy to improve specific traits, such as resistance to varroa, which can be difficult or expensive to phenotype. However, if used during several generations in a closed population, monoandrous mating increases the inbreeding level of queens much more than polyandrous mating, which is a strong limitation of this strategy.

To assess whether the risk of epilepsy is higher in offspring of mothers with epilepsy than in offspring of fathers with epilepsy.
In a prospective population-based register study, we considered all singletons born in Denmark between 1981 and 2016 (N = 1,754,742). From the Danish National Patient Register since 1977, we identified epilepsy diagnoses in all study participants and their family members. Cox regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CI), adjusted for relevant confounders.
We included 1,754,742 individuals contributing > 30 million person-years of follow-up. The incidence rate of epilepsy in offspring of unaffected parents was 78.8 (95% CI: 77.8-79.8) per 100,000 person-years, while the corresponding rate in offspring with an affected father was 172 per 100,000 person-years (95% CI: 156-187) and in offspring with an affected mother was 260 per 100,000 person-years (95% CI: 243-277). Having an affected mother was associated with a 1.45-fold (95% CI: 1.30-1.63) higher risk of epilepsy in the offspring, compared to having an affected father. This maternal effect was found both in male (HR = 1.39, 95% CI: 1.19-1.62) and female offspring (HR = 1.53, 95% CI: 1.30-1.80), and across various ages at onset in the offspring. The maternal effect was also found in familial epilepsies (i.e. where the affected parent had an affected sibling; HR = 1.50, 95% CI: 1.04-2.16).
We found a clear maternal effect on offspring risk of epilepsy in this nationwide cohort study.

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

The mitochondrial DNA (mDNA) 3243A>G variant is the most common pathogenic variant of the mDNA. To interpret results of clinical trials in mitochondrial disease, it is important to have a clear understanding of the natural course of disease. To obtain more insight into the disease burden and the progression of disease in carriers of the mDNA 3243 A>G variant, we followed a cohort of 151 carriers from 61 families prospectively for up to 6 years.
The disease severity was scored using the Newcastle Mitochondrial Disease Adult Scale (NMDAS), including SF-36 quality of life (QoL) scores. Heteroplasmy levels were measured in urinary epithelial cells (UEC), leucocytes and saliva. The progression of the disease was studied using linear mixed model analysis.
One hundred twenty-four carriers (out of 151) were symptomatic. Four clinical groups were identified: 1) classical mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (n=7), 2) maternally inherited diabetes deafness syndrome (n=60), 3) \'other\' (n=57) and 4) dormant carriers (n=27). A yearly increase of NMDAS score of 0.47 point was measured in the total group. Heteroplasmy levels in both leucocytes and UEC were only weakly correlated with disease severity. Physical QoL declined with age. The most important determinants of QoL decline were hearing loss, speech problems, exercise intolerance, gait instability, psychiatric problems and gastrointestinal involvement.
The mDNA 3243 A>G variant causes a slowly progressive disease, with a yearly increase of NMDAS score of ~0.5 point overall with the clinical phenotype being the only determinant of disease progression.

Pooling semen of multiple boars is commonly used in swine production systems. Compared with single boar systems, this technique changes family structure creating maternal half-sib families. The aim of this simulation study was to investigate how pooling semen affects the accuracy of estimating direct and maternal effects for individual piglet birth weight, in purebred pigs. Different scenarios of pooling semen were simulated by allowing the same female to mate from 1 to 6 boars, per insemination, whereas litter size was kept constant (N = 12). In each pooled boar scenario, genomic information was used to construct either the genomic relationship matrix (G) or to reconstruct pedigree in addition to G. Genotypes were generated for 60,000 SNPs evenly distributed across 18 autosomes. From the 5 simulated generations, only animals from generations 3 to 5 were genotyped (N = 36,000). Direct and maternal true breeding values (TBV) were computed as the sum of the effects of the 1,080 QTLs. Phenotypes were constructed as the sum of direct TBV, maternal TBV, an overall mean of 1.25 kg, and a residual effect. The simulated heritabilities for direct and maternal effects were 0.056 and 0.19, respectively, and the genetic correlation between both effects was -0.25. All simulations were replicated 5 times. Variance components and direct and maternal heritability were estimated using average information REML. Predictions were computed via pedigree-based BLUP and single-step genomic BLUP (ssGBLUP). Genotyped littermates in the last generation were used for validation. Prediction accuracies were calculated as correlations between EBV and TBV for direct (accdirect) and maternal (accmat) effects. When boars were known, accdirect were 0.21 (1 boar) and 0.26 (6 boars) for BLUP, whereas for ssGBLUP, they were 0.38 (1 boar) and 0.43 (6 boars). When boars were unknown, accdirect was lower in BLUP but similar in ssGBLUP. For the scenario with known boars, accmat was 0.58 and 0.63 for 1 and 6 boars, respectively, under ssGBLUP. For unknown boars, accmat was 0.63 for 2 boars and 0.62 for 6 boars in ssGBLUP. In general, accdirect and accmat were lower in the single-boar scenario compared with pooled semen scenarios, indicating that a half-sib structure is more adequate to estimate direct and maternal effects. Using pooled semen from multiple boars can help us to improve accuracy of predicting maternal and direct effects when maternal half-sib families are larger than 2.

We report a case of familial small supernumerary marker chromosome 15 in a phenotypically normal female with 4 recurrent spontaneous abortions and a healthy child. The initial karyotype showed a small, bisatellited, apparently metacentric marker chromosome, 47,XX,+idic(15)(q11.1), maternally inherited. The proband\'s mother was mosaic for the idic(15)(q11.1) without pregnancy loss. Reexamination of the proband\'s karyotype revealed cryptic mosaicism for 1 ring and 1 minute chromosome derived de novo from chromosome 9 in 2% of the metaphases. In FISH analysis, the patient\'s karyotype was mos 47,XX,+idic(15)(q11.1)mat[100]/49,XX,+idic(15)(q11.1)mat,+r(9;9;9;9),+der(9)dn[2]. The second spontaneous abortion had trisomy 9 (47,XX,+9); the third had mosaic trisomy 9 in 21% of the nuclei and isodicentric chromosome 15 in 36% of the nuclei (mos 48,XN,+9,+idic(15)(q11.1)/47,XN,+9/47,XN,+idic(15)(q11.1)/46,XN). The first and fourth abortions were not cytogenetically studied. The cause of the spontaneous abortions in this patient is likely the cryptic mosaicism for ring and minute chromosomes 9, and gonadal mosaicism is most probable, due to the 2 abortions.