Genetics

Correction to: Splicing mutations in human genetic disorders: examples, detection, and confirmation The original version on this paper contained an error. The first names and last names of Anna Abramowicz and Monika Gos are inadvertently interchanged and are incorrectly displayed in indexing sites. The correct names are presented above.

Co-treatment with probucol does not improve lung pathology in hydroxypropyl-β-cyclodextrin-treated Npc1 −/− mice Abstract We previously reported the altered pulmonary function and pathology found in the mouse model of infantile Niemann-Pick C1 disease, the Npc1−/− mouse. Despite its salutary properties on brain and liver parameters, we did not find efficacious effects of hydroxypropyl-β-cyclodextrin (HPBCD) on pulmonary pathology. Since we had previously shown the beneficial effects of probucol on the somatic phenotype in the Npc1−/− mice, we have now studied the effects of combined therapy with HPBCD and probucol on the lung with mostly negative results. Body weight and lung weight for body weight were increased in parallel while inspiratory capacity for body weight was markedly decreased. Other physical, biochemical, and pulmonary function parameters were not much changed. There were trends towards improved lung elastance (p = 0.09) and compliance (p = 0.07).

Zebrafish breeding program: genetic parameters estimates for growth traits Abstract The objective of this study was to evaluate the genetic parameters of two generations of zebrafish breeding program. The base population was formed by crossing individuals of six commercial stocks of zebrafish, resulting in a nucleus with 60 families. Two generations were evaluated, with a total of 780 and 781 individuals for the first and second generation, respectively. The selection was made based on the mean genetic value of each family, followed by mass selection of the breeders. Mathematical models that considered the fixed (age, density in the larval stage, sex, and generation) and random (animal additive genetics, common to full-sibs, and residual) effects were evaluated using BLUPF90 program family. Weight and total length were used as response variables. Total length was the best selection criterion because it had a higher heritability (0.30) than weight (0.22). There was a high common to full-sib effect, especially in the first generation of animals. For second-generation data, the heritability was 0.26 for total length, as well as a lower common to full-sib effect for length. The best model obtained for this evaluation was considering all effects, being age and density as first and second polynomial, respectively. The genetic and phenotypic correlations for weight and length were 0.87 and 0.75, respectively. These results indicate that genetic breeding using total length as the selection criterion may produce a larger and heavier zebrafish strain.

New QTL for resistance to Puccinia polysora Underw in maize Abstract Southern corn rust (SCR) is a prevalent foliar disease in maize. Deployment of resistant cultivars is an effective way to control SCR. In this study, resistance to SCR was evaluated in a BC1RIL population comprising 118 lines grown under three different field conditions. Combined with a genetic map constructed from 1635 SNP markers obtained from the maize 9.4 K SNP Affymetrix® Axiom® Genotyping Array, single quantitative trait loci (QTL) were mapped on chromosomes 4, 9, and 10, respectively. The QTL on chromosome 4 (qSCR4.08) and chromosome 9 (qSCR9.04) were stable across multiple environments, and each explained more than 10% of the phenotypic variation. The stable QTL detected could be desirable sources of SCR resistance in maize-breeding programs.

Genotype by environment interaction using AMMI model and estimation of additive and epistasis gene effects for 1000-kernel weight in spring barley ( Hordeum vulgare L.) Abstract The objective of this study was to assess genotype by environment interaction for 1000-kernel weight in spring barley lines grown in South Poland by the additive main effects and multiplicative interaction model. The study comprised of 32 spring barley (Hordeum vulgare L.) genotypes (two parental genotypes—breeding line 1 N86 and doubled haploid (DH) line RK63/1, and 30 DH lines derived from F1 hybrids), evaluated at six locations in a randomized complete block design, with three replicates. 1000-kernel weight ranged from 24.35 g (for R63N/42 in 2011) to 61.46 g (for R63N/18 in 2008), with an average of 44.80 g. AMMI analyses revealed significant genotype and environmental effects as well as GE interaction with respect to 1000-kernel weight. In the analysis of variance, 16.86% of the total 1000-kernel weight variation was explained by environment, 32.18% by differences between genotypes, and 24.50% by GE interaction. The lines R63N/61, R63N/22, and R63N/1 are recommended for further inclusion in the breeding program because their stability and the highest averages of 1000-kernel weight. The total additive effect of all genes controlling the trait and the total epistasis effect of 1000-kernel weight were estimated. Additive gene action effects based on DH lines were always larger that this parameter estimated on the basis of parental lines. Estimates of additive gene action effects based on the all DH lines were significantly larger than zero in each year of study. Epistasis effects based on all DH lines were statistically significant in 2011 and 2013.

Comparing assignment-based approaches to breed identification within a large set of horses Abstract Considering the extensive data sets and statistical techniques, animal breeding embodies a branch of machine learning that has a constantly increasing impact on breeding. In our study, information regarding the potential of machine learning and data mining within a large set of horses and breeds is presented. The individual assignment methods and factors influencing the success rate of the procedure are compared at the Czech population scale. The fixation index values ranged from 0.057 (HMS1) to 0.144 (HTG6), and the overall genetic differentiation amounted to 8.9% among the breeds. The highest genetic divergence (FST = 0.378) was established between the Friesian and Equus przewalskii; the highest degree of gene migration was obtained between the Czech and Bavarian Warmblood (Nm = 14,302); and the overall global heterozygote deficit across the populations was 10.4%. The eight standard methods (Bayesian, frequency, and distance) using GeneClass software and almost all mainstream classification algorithms (Bayes Net, Naive Bayes, IB1, IB5, KStar, JRip, J48, Random Forest, Random Tree, PART, MLP, and SVM) from the WEKA machine learning workbench were compared by utilizing 314,874 real allelic data sets. The Bayesian method (GeneClass, 89.9%) and Bayesian network algorithm (WEKA, 84.8%) outperformed the other techniques. The breed genomic prediction accuracy reached the highest value in the cold-blooded horses. The overall proportion of individuals correctly assigned to a population depended mainly on the breed number and genetic divergence. These statistical tools could be used to assess breed traceability systems, and they exhibit the potential to assist managers in decision-making as regards breeding and registration.

A novel WDR62 missense mutation in microcephaly with abnormal cortical architecture and review of the literature Abstract Autosomal recessive primary microcephaly (MCPH) is a group of rare neurodevelopmental diseases with severe microcephaly at birth. One type of the disorder, MCPH2, is caused by biallelic mutations in the WDR62 gene, which encodes the WD repeat–containing protein 62. Patients with WDR62 mutation may have a wide range of malformations of cortical development in addition to congenital microcephaly. We describe two patients, a boy and a girl, with severe congenital microcephaly, global developmental delay, epilepsy, and failure to thrive. MRI showed hemispherical asymmetry, diffuse pachygyria, thick gray matter, indistinct gray-white matter junction, and corpus callosum and white matter hypoplasia. Whole exome sequencing revealed the same novel homozygous missense mutation, c.668T>C, p.Phe223Ser in exon 6 of the WDR62 gene. The healthy parents were heterozygous for this mutation. The mutation affects a highly conserved region in one of the WD repeats of the WDR62 protein. Haplotype analysis showed genetic relatedness between the families of the patients. Our findings expand the spectrum of mutations randomly distributed in the WDR62 gene. A review is also provided of the brain malformations described in WDR62 mutations in association with congenital microcephaly.

A single enzyme PCR-RFLP assay targeting V1-V3 region of 16S rRNA gene for direct identification of Alicyclobacillus acidoterrestris from other Alicyclobacillus species Abstract Alicyclobacillus acidoterrestris is considered to be one of the most important target microorganisms in quality control of heat-processed acidic foods. This species can cause spoilage by forming spores with very high heat resistance; however, no gas production or visible changes occur in the contaminated product during storage. Thus, the differentiation of A. acidoterrestris from other Alicyclobacillus species is of great importance. Τhe present study aims to find a rapid method for the identification of A. acidoterrestris. To achieve this, 78 Alicyclobacillus isolates were subjected to PCR-RFLP (restriction fragment length polymorphism). Specifically, PCR products of amplified V1-V3 region of the 16S rRNA gene were digested with restriction endonuclease HhaI. According to the obtained results, all A. acidoterrestris isolates showed similar restriction fragments of the 16S rRNA gene and different from A. acidocaldarius and A. hesperidum. In conclusion, a single enzyme PCR-RFLP assay was developed and showed rapid, inexpensive and direct identification of Alicyclobacillus isolates. The application of this method will be useful to identify this contaminant in fruit juices.

Novel data on growth phenotype and causative genotypes in 29 patients with Morquio (Morquio-Brailsford) syndrome from Central-Eastern Europe Abstract Mucopolysaccharidosis type IVA, also known as Morquio (Morquio-Brailsford) syndrome results from accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S), whereas the primary cause is mutations in the gene encoding galactosamine (N-acetyl)-6-sulfatase (GALNS). Phenotypically it seems to be a well-defined condition, with two main clinical forms: mild (attenuated) and severe, which are determined based on a combination of symptoms, i.e., enzymatic activity of GALNS, age of onset, and symptom severity. Nevertheless, the natural history of MPSIVA in relation to specific anthropometric parameters (growth, head circumference, body proportions, and face phenotype) is not precisely characterized. The aim of our work was to analyze the aforementioned anthropometric parameters, including correlation to molecular data (causative GALNS mutations).

Copy number variation of bovine SHH gene is associated with body conformation traits in Chinese beef cattle Abstract Sonic Hedgehog (Shh) regulates many key developmental processes during vertebrate limb development, fat formation, and skeletal tissue regeneration. Current whole genome sequencing data have identified a copy number variation mapping to bovine Sonic Hedgehog gene (SHH-CNV). The object of this study was to characterize the SHH-CNV distributions in 648 individuals from 11 Chinese cattle populations and further to investigate the associations of the copy number changes with gene expression and cattle growth traits. The SHH-CNV showed a high variance within Chinese indigenous yellow cattle. Compared to yak and dairy cattle, the beef cattle like Luxi and Xianan breed had significantly higher median copy numbers, suggesting the diversity of SHH-CNV in beef cattle selections. The negative correlation of SHH-CNV with SHH transcriptional level in adult adipose tissue (P < 0.01) indicated the dosage effects of SHH-CNV related to bovine fat formation. Association analysis of SHH-CNV and body size traits was conducted in five breeds. The results revealed that the copy number gain type of SHH-CNV exhibited significantly better chest depth in 24 months old Qinchuan cattle, and better body weight, body length, and chest girth in 18 months old Nanyang cattle, whereas the normal copy number had superior chest girth and body weight in adult Jinnan cattle (P < 0.05 or P < 0.01). In summary, this research uncovered meaningful effects of SHH-CNV on gene expression and cattle phenotypic traits, indicating its potential applications for genetic improvement of beef cattle.