A comparative whole genome sequencing analysis identified a candidate locus for lack of operculum in cultivated gilthead seabream (Sparus aurata).

The gilthead seabream (Sparus aurata, Sparidae family) is commonly used for aquaculture. Despite its great economic value, several problems in its cultivation remain. One of the major concerns is the high frequency of morphological abnormalities occurring during the early developmental stages. Partial and/or total lack of operculum is the most frequent anomaly affecting the fish cranial region. The existence of genetic factors that can at least partially determine this defect has been hypothesized. In this work, two DNA pools of highly related fry, one composed of normal-looking (control) fish and the other lacking an operculum (case), were constructed and whole-genome resequencing data produced from the two were compared. The analysis revealed a 1 Mb region on chromosome 2 with higher heterozygosity in the lack of operculum DNA pool than in the control DNA pool, consistent with the enrichment, in the first DNA pool, of one or more haplotypes causing or predisposing to the defect together with other normal haplotypes. A window-based FST analysis between the two DNA pools indicated that the same region had the highest divergence score. This region contained 2921 SNVs, 10 of which, with predicted high impacts (three splice donor and seven stop-gained variants), were detected in novel genes that are homologous to calcium-sensing receptor-like genes, probably involved in bone development. Other studies are needed to clarify the genetic mechanisms involved in predisposing fry to this deformity and then to identify associated markers that could be used in breeding programs to reduce the frequency of this defect in the broodstock.

Identification of a major locus determining a pigmentation defect in cultivated gilthead seabream (Sparus aurata).

The gilthead seabream (Sparus aurata) is an important cultivated species in the Mediterranean area. A major problem for the gilthead seabream aquaculture sector derives from the high frequency of phenotypic abnormalities, including discolorations. In this study, we applied a whole-genome resequencing approach to identify a genomic region affecting a pigmentation defect that occurred in a cultivated S. aurata population. Two equimolar DNA pools were constructed using DNA extracted from 30 normally coloured and 21 non-pigmented fish collected among the offspring of the same broodstock nucleus. Whole-genome resequencing reads from the two DNA pools were aligned to the S. aurata draft genome and variant calling was performed. A whole-genome heterozygosity scan from single pool sequencing data highlighted a peak of reduced heterozygosity of approximately 5 Mbp on chromosome 6 in the non-pigmented pool that was not present in the normally coloured pool. The comparison of the non-pigmented with the normally coloured fish using a whole-genome FST analysis detected three main regions within the coordinates previously detected with the heterozygosity analysis. The results support the presence of a major locus affecting this discoloration defect in this fish population. The results of this study have practical applications, including the possibility of eliminating this defect from the breeding stock, with direct economic advantages derived from the reduction of discarded fry. Other studies are needed to identify the candidate gene and the causative mutation, which could add information to understand the complex biology of fish pigmentation.

Marker discovery and associations with ß-carotene content in Indian dairy cattle and buffalo breeds.

Vitamin A is essential for human health, but current intake levels in many developing countries such as India are too low due to malnutrition. According to the World Health Organization, an estimated 250 million preschool children are vitamin A deficient globally. This number excludes pregnant women and nursing mothers, who are particularly vulnerable. Efforts to improve access to vitamin A are key because supplementation can reduce mortality rates in young children in developing countries by around 23%. Three key genes, BCMO1, BCO2, and SCARB1, have been shown to be associated with the amount of ß-carotene (BC) in milk. Whole-genome sequencing reads from the coordinates of these 3 genes in 202 non-Indian cattle (141 Bos taurus, 61 Bos indicus) and 35 non-Indian buffalo (Bubalus bubalis) animals from several breeds were collected from data repositories. The number of SNP detected in the coding regions of these 3 genes ranged from 16 to 26 in the 3 species, with 5 overlapping SNP between B. taurus and B. indicus. All these SNP together with 2 SNP in the upstream part of the gene but already present in dbSNP (https://www.ncbi.nlm.nih.gov/projects/SNP/) were used to build a custom Sequenom array. Blood for DNA and milk samples for BC were obtained from 2,291 Indian cows of 5 different breeds (Gir, Holstein cross, Jersey Cross, Tharparkar, and Sahiwal) and 2,242 Indian buffaloes (Jafarabadi, Murrah, Pandharpuri, and Surti breeds). The DNA was extracted and genotyped with the Sequenom array. For each individual breed and the combined breeds, SNP with an association that had a P-value <0.3 in the first round of linear analysis were included in a second step of regression analyses to determine allele substitution effects to increase the content of BC in milk. Additionally, an F-test for all SNP within gene was performed with the objective of determining if overall the gene had a significant effect on the content of BC in milk. The analyses were repeated using a Bayesian approach to compare and validate the previous frequentist results. Multiple significant SNP were found using both methodologies with allele substitution effects ranging from 6.21 (3.13) to 9.10 (5.43) µg of BC per 100 mL of milk. Total gene effects exceeded the mean BC value for all breeds with both analysis approaches. The custom panel designed for genes related to BC production demonstrated applicability in genotyping of cattle and buffalo in India and may be used for cattle or buffalo from other developing countries. Moreover, the recommendation of selection for significant specific alleles of some gene markers provides a route to effectively increase the BC content in milk in the Indian cattle and buffalo populations.

Enhanced coupling of broadband light into amorphous silicon via periodic nanoplasmonic arrays.

Achieving enhanced coupling of solar radiation over the full range of the silicon absorption spectrum up to the bandgap is essential for increased efficiency of solar cells, especially thin film versions. While many designs for enhancing trapping of radiation have been explored, detailed measurements of light scattering inside silicon cells is still lacking. Here, we demonstrate experimentally and computationally that plasmonic-assisted localized and traveling modes can efficiently couple red and infrared radiation into ultrathin amorphous silicon (a-Si) layers. Utilizing patterned periodic arrays of aluminum nanostructures on thin a-Si, we perform specular and diffuse reflectivity and transmission measurements over a broad spectrum. Based on these results, we are able to separate parasitic absorption in aluminum plasmonic arrays from enhanced light absorption in the 200 nm thick amorphous silicon layer, as compared to a blank silicon layer. We discover a very efficient near-infrared a-Si absorption mechanism that occurs at the transition from the radiative to evanescent diffractive coupling, analogous to earlier surface-enhanced infrared studies. These results represent a direct demonstration of enhanced radiation coupling into silicon due to large angle scattering and show a path forward to improved ultrathin solar cell efficiency.

Genome-wide scan reveals divergent selection among taurine and zebu cattle populations from different regions.

In this study, to identify genomic signatures of divergent selection, we genotyped 10 cattle breeds/populations (n = 275), representing eight Ethiopian cattle populations (n = 229) and two zebu populations (n = 46) adapted to tropical and sub-tropical environments, using the high-density single-nucleotide polymorphisms (SNPs) derived mainly from Bos indicus breeds, and using five reference taurine breeds (n = 212). Population genetic differentiation (FST ) values across sliding windows were estimated between zebu and reference combined taurine breeds. The most differentiated regions (FST  ≥ 0.53), representing the top 1% smoothed FST values, were considered to represent regions under diversifying selection. In total, 285 and 317 genes were identified in the comparisons of Ethiopian cattle with taurine and Asian zebu with taurine respectively. Some of these genes are involved in stress responses/thermo-tolerance and DNA damage repair (HSPA4, HSF1, CMPK1 and EIF2AK4), pigmentation (ERBB3 and MYO1A), reproduction/fertility (UBE2D3, ID3 and PSPC1), immune response (PIK3CD and AKIRIN2) and body stature and size (MBP2, LYN and NPM1). Additionally, the candidate genes were associated with functional terms (e.g. cellular response to stress, DNA repair, inflammatory response) important for physiological adaptation to environmental stresses. The results of our study may shed light on the influence of artificial and natural selection in shaping the genomic diversity of modern cattle breeds and also may serve as a basis for further genetic investigation of traits of tropical adaptation in cattle.

Genomic investigation of piglet resilience following porcine epidemic diarrhea outbreaks.

Porcine epidemic diarrhea virus (PEDV) belongs to the Coronaviridae family and causes malabsorptive watery diarrhea, vomiting, dehydration and imbalanced blood electrolytes in pigs. Since the 1970s, PED outbreaks have become a source of problems in pig producing countries all over the world, causing large economic losses for pig producers. Although the infection in adults is not fatal, in naïve suckling piglets mortality is close to 100%. In this study, we investigated genome-wide differences between dead and recovered suckling piglets from commercial farms after PED outbreaks. Samples from 262 animals (156 dead and 106 recovered) belonging to several commercial lines were collected from five different farms in three different countries (USA, Canada and Germany) and genotyped with the porcine 80K SNP chip. Mean Fst value was calculated in 1-Mb non-overlapping windows between dead and recovered individuals, and the results were normalized to find differences within the comparison. Seven windows with high divergence between dead and recovered were detected-five on chromosome 2, one on chromosome 4 and one on chromosome 15-in total encompassing 152 genes. Several of these genes are either under- or overexpressed in many virus infections, including Coronaviridae (such as SARS-CoV). A total of 32 genes are included in one or more Gene Ontology terms that can be related to PED development, such as Golgi apparatus, as well as mechanisms generally linked to resilience or diarrhea development (cell proliferation, ion transport, ATPase activity). Taken together this information provides a first genomic picture of PEDV resilience in suckling piglets.

Genomic analysis of Ugandan and Rwandan chicken ecotypes using a 600 k genotyping array.

BACKGROUND: Indigenous populations of animals have developed unique adaptations to their local environments, which may include factors such as response to thermal stress, drought, pathogens and suboptimal nutrition. The survival and subsequent evolution within these local environments can be the result of both natural and artificial selection driving the acquisition of favorable traits, which over time leave genomic signatures in a population. This study's goals are to characterize genomic diversity and identify selection signatures in chickens from equatorial Africa to identify genomic regions that may confer adaptive advantages of these ecotypes to their environments. RESULTS: Indigenous chickens from Uganda (n = 72) and Rwanda (n = 100), plus Kuroilers (n = 24, an Indian breed imported to Africa), were genotyped using the Axiom® 600 k Chicken Genotyping Array. Indigenous ecotypes were defined based upon location of sampling within Africa. The results revealed the presence of admixture among the Ugandan, Rwandan, and Kuroiler populations. Genes within runs of homozygosity consensus regions are linked to gene ontology (GO) terms related to lipid metabolism, immune functions and stress-mediated responses (FDR < 0.15). The genes within regions of signatures of selection are enriched for GO terms related to health and oxidative stress processes. Key genes in these regions had anti-oxidant, apoptosis, and inflammation functions. CONCLUSIONS: The study suggests that these populations have alleles under selective pressure from their environment, which may aid in adaptation to harsh environments. The correspondence in gene ontology terms connected to stress-mediated processes across the populations could be related to the similarity of environments or an artifact of the detected admixture.

Single nucleotide variant discovery of highly inbred Leghorn and Fayoumi chicken breeds using pooled whole genome resequencing data reveals insights into phenotype differences.

BACKGROUND: Analyses of sequence variants of two distinct and highly inbred chicken lines allowed characterization of genomic variation that may be associated with phenotypic differences between breeds. These lines were the Leghorn, the major contributing breed to commercial white-egg production lines, and the Fayoumi, representative of an outbred indigenous and robust breed. Unique within- and between-line genetic diversity was used to define the genetic differences of the two breeds through the use of variant discovery and functional annotation. RESULTS: Downstream fixation test (F ST ) analysis and subsequent gene ontology (GO) enrichment analysis elucidated major differences between the two lines. The genes with high F ST values for both breeds were used to identify enriched gene ontology terms. Over-enriched GO annotations were uncovered for functions indicative of breed-related traits of pathogen resistance and reproductive ability for Fayoumi and Leghorn, respectively. CONCLUSIONS: Variant analysis elucidated GO functions indicative of breed-predominant phenotypes related to genomic variation in the lines, showing a possible link between the genetic variants and breed traits.

Broadband optical switch based on liquid crystal dynamic scattering.

This work demonstrates a novel broadband optical switch, based on dynamic-scattering effect in liquid crystals (LCs). Dynamic-scattering-mode technology was developed for display applications over four decades ago, but was displaced in favor of the twisted-nematic LCs. However, with the recent development of more stable LCs, dynamic scattering provides advantages over other technologies for optical switching. We demonstrate broadband polarization-insensitive attenuation of light directly passing thought the cell by 4 to 5 orders of magnitude at 633 nm. The attenuation is accomplished by light scattering to higher angles. Switching times of 150 µs to 10% transmission have been demonstrated. No degradation of devices is found after hundreds of switching cycles. The light-rejection mechanism is due to scattering, induced by disruption of LC director orientation with dopant ion motion with an applied electric field. Angular dependence of scattering is characterized as a function of bias voltage.

Multiple genomic signatures of selection in goats and sheep indigenous to a hot arid environment.

Goats and sheep are versatile domesticates that have been integrated into diverse environments and production systems. Natural and artificial selection have shaped the variation in the two species, but natural selection has played the major role among indigenous flocks. To investigate signals of natural selection, we analyzed genotype data generated using the caprine and ovine 50K SNP BeadChips from Barki goats and sheep that are indigenous to a hot arid environment in Egypt's Coastal Zone of the Western Desert. We identify several candidate regions under selection that spanned 119 genes. A majority of the genes were involved in multiple signaling and signal transduction pathways in a wide variety of cellular and biochemical processes. In particular, selection signatures spanning several genes that directly or indirectly influenced traits for adaptation to hot arid environments, such as thermo-tolerance (melanogenesis) (FGF2, GNAI3, PLCB1), body size and development (BMP2, BMP4, GJA3, GJB2), energy and digestive metabolism (MYH, TRHDE, ALDH1A3), and nervous and autoimmune response (GRIA1, IL2, IL7, IL21, IL1R1) were identified. We also identified eight common candidate genes under selection in the two species and a shared selection signature that spanned a conserved syntenic segment to bovine chromosome 12 on caprine and ovine chromosomes 12 and 10, respectively, providing, most likely, the evidence for selection in a common environment in two different but closely related species. Our study highlights the importance of indigenous livestock as model organisms for investigating selection sweeps and genome-wide association mapping.

Traumatic asphyxia--fatal accident in an automatic revolving door.

Due to continuing modernisation, the number of automatic doors in routine use, including powered revolving doors, has increased in recent years. Automatic revolving doors are found mostly in department stores, airports, railway stations and hospitals. Although safety arrangements and guidelines concerning the installation of automatic doors are in existence, their disregard in conjunction with obsolete or incorrect installation can lead to fatal accidents. In this report, a 19-month-old boy is described whose right arm was caught between the elements of an automatic revolving door. As a direct result of rescue attempts, the child's body was drawn further into the narrow gap between elements of the door. To get the boy's body out of the 4-cm-wide gap between the fixed outer wall of the revolving door and the revolving inner, back-up batteries had to be disconnected so as to stop the electrical motor powering the door. Cardiopulmonary resuscitation was begun immediately after the rescue but was unsuccessful; the child was declared dead at the hospital he was taken to. The cause of death was a combination of compression-related skull and brain injury together with thoracic compression. This case shows an outstanding example of the preventive aspect as a special task of forensic medicine. Additionally, it serves as a warning for the correct installation and use of automatic revolving doors. Even so, small children should not use these doors on their own, but only with an alert companion, so as to prevent further fatal accidents of this sort.

Effects of dietary fiber on cecal short-chain fatty acid and cecal microbiota of broiler and laying-hen chicks.

This experiment was conducted to evaluate the effects of feeding dietary fiber on cecal short-chain fatty acid (SCFA) concentration and cecal microbiota of broiler and laying-hen chicks. The lower fiber diet was based on corn-soybean meal (SBM) and the higher fiber diet was formulated using corn-SBM-dried distillers grains with solubles (DDGS) and wheat bran to contain 60.0 g/kg of both DDGS and wheat bran from 1 to 12 d and 80.0 g/kg of both DDGS and wheat bran from 13 to 21 d. Diets were formulated to meet or exceed NRC nutrient requirements. Broiler and laying-hen chicks were randomly assigned to the high and low fiber diets with 11 replicates of 8 chicks for each of the 4 treatments. One cecum from 3 chicks was collected from each replicate: one cecum underwent SCFA concentration analysis, one underwent bacterial DNA isolation for terminal restriction fragment length polymorphism (TRFLP), and the third cecum was used for metagenomics analyses. There were interactions between bird line and dietary fiber for acetic acid (P = 0.04) and total SCFA (P = 0.04) concentration. There was higher concentration of acetic acid (P = 0.02) and propionic acid (P < 0.01) in broiler chicks compared to laying-hen chicks. TRFLP analysis showed that cecal microbiota varied due to diet (P = 0.02) and chicken line (P = 0.03). Metagenomics analyses identified differences in the relative abundance of Helicobacter pullorum and Megamonas hypermegale and the genera Enterobacteriaceae, Campylobacter, Faecalibacterium, and Bacteroides in different treatment groups. These results provide insights into the effect of dietary fiber on SCFA concentration and modulation of cecal microbiota in broiler and laying-hen chicks.

Identification of species-specific novel transcripts in pig reproductive tissues using RNA-seq.

Although structural properties of the porcine reproductive system are shared by many placental mammals, some combination of these properties is unique to pigs. To explore whether genomic elements specific to pigs could potentially underlie this uniqueness, we made the first step to identify novel transcripts in two representative pig reproductive tissues by the technique of massively parallel sequencing. To automate the whole process, we built a computational pipeline, which can also be easily extended for similar studies in other species. In total, 5516 and 9061 novel transcripts were found, and 159 and 252 novel transcripts appear to be specific to pigs for the placenta and testis respectively. Furthermore, these novel transcripts were found to be enriched in quantitative trait loci (QTL) regions for reproduction traits in pigs. We validated eight of these novel transcripts by quantitative real-time PCR. With respect to their genomic organization and their functional relationship to reproduction, these transcripts need to be further validated and explored in various pig breeds to better comprehend the relevant aspects of pig physiology that contribute to reproductive performance.

Genomic analysis of the differential response to experimental infection with porcine circovirus 2b.

Porcine circovirus type 2 (PCV2) is the etiological agent of a group of associated diseases (PCVAD) that affect production efficiency and can lead to mortality. Using different crossbred lines of pigs, we analyzed host genetic variation of viral load, immune response and weight change following experimental infection with a PCV2b strain (n = 386). Pigs expressed variation in the magnitude and initiation of viremia and immune response recorded weekly until 28 days post-infection. A higher viral load was correlated with weight gain (r = -0.26, P < 0.0001) and presence of PCV2-specific antibodies (IgM, r = 0.26-0.34, P < 0.0001; IgG, r = 0.17-0.20, P < 0.01). In genome-wide association analyses of the responses at different time points, the proportions of phenotypic variation explained by combined effects of 56 433 SNPs were 34.8-59.4% for viremia, 10.1-59.5% for antibody response and 5.6-14.9% for weight change. Relationships between genomic prediction of overall viral load and weight gain during the first weeks of challenge were negative (-0.21 and -0.24 respectively, P < 0.0001). Individuals that carried more favorable alleles across three SNPs on SSC9 (0.60 Mb) and SSC12 (6.8 and 18.2 Mb) partially explained this relationship, having lower viral load (P < 0.0001); lower viremia at day 14 (P < 0.0001), day 21 (P < 0.01) and day 28 (P < 0.05) and greater overall average daily gain during infection (ADGi ; P < 0.01), ADGi at week 3 (P < 0.001) and week 4 (P < 0.01). These additive genetic relationships could lead to molecular solutions to improve animal health and reduce production costs.

A genome-wide association study for canine cryptorchidism in Siberian Huskies.

Cryptorchidism is a condition whereby one or both testes fail to descend into the scrotal sac. Here, we performed a genome-wide association study (GWAS) with both a case-control analysis using the GEMMA software accounting for population structure and a BayesB approach in the GenSel software applied to every 1 Mb window of SNPs or haplotypes. The haplotypes were constructed from a genealogical tree using the population of 204 Siberian Huskies. The BayesB analyses identified six putative genomic candidate regions on CFA6, 9, 24, 27 and X. These regions explained a high percentage of genetic variance when compared with other genomic regions. The positional candidate genes Q9TSI5_CANFA (matrix metalloproteinase 9 precursor) on CFA24, ADAMTS20 (ADAM metallopeptidase with thrombospondin type 1 motif, 20) on CFA27 and MID1IP1 (MID1 interacting protein 1) on CFAX are known to be functionally related to extracellular matrix remodelling, which might be important for gubernaculum elongation and thus interrupting normal testicular descent. Further mutation screening in these candidate regions on CFA6, 9, 24, 27 and X is needed. Next generation sequencing will help to uncover rare variants associated with cryptorchidism in this dog population.

Child abuse inflicted by small children.

In cases of child abuse, usually, the parents are initial suspects. A common explanation of the parents is that the injuries were caused by a sibling. Child-on-child violence is reported to be very rare in children less than 5 years of age, and thorough investigation by the police, child protective services, and medicolegal examinations are needed to proof or disproof the parents' statement. We report two cases of physical abuse of infants by small children.

Genome-wide prediction of age at puberty and reproductive longevity in sows.

Traditional selection for sow reproductive longevity is ineffective due to low heritability and late expression of the trait. Incorporation of DNA markers into selection programs is potentially a more practical approach for improving sow lifetime productivity. Using a resource population of crossbred gilts, we explored pleiotropic sources of variation that influence age at puberty and reproductive longevity. Of the traits recorded before breeding, only age at puberty significantly affected the probability that females would produce a first parity litter. The genetic variance explained by 1-Mb windows of the sow genome, compared across traits, uncovered regions that influence both age at puberty and lifetime number of parities. Allelic variants of SNPs located on SSC5 (27-28 Mb), SSC8 (36-37 Mb) and SSC12 (1.2-2 Mb) exhibited additive effects and were associated with both early expression of puberty and a greater than average number of lifetime parities. Combined analysis of these SNPs showed that an increase in the number of favorable alleles had positive impact on reproductive longevity, increasing number of parities by up to 1.36. The region located on SSC5 harbors non-synonymous alleles in the arginine vasopressin receptor 1A (AVPR1A) gene, a G-protein-coupled receptor associated with social and reproductive behaviors in voles and humans and a candidate for the observed effects. This region is characterized by high levels of linkage disequilibrium in different lines and could be exploited in marker-assisted selection programs across populations to increase sow reproductive longevity.

Investigation of the impact of biogeographic ancestry on DNA methylation based age predictions comparing a Middle East and a Central European population.

DNA methylation based age prediction is a new method in the toolbox of forensic genetics. Typically, the method is applied in the course of police investigation e.g. to predict the age of an unknown person that has left a biological trace at a crime scene. The method can also be used to answer other forensic questions, for example to estimate the age of unknown human bodies in the course of the identification process. In the present study, we tested for a potential impact of biogeographic ancestry (BGA) on age predictions using five age dependent methylated CpG sites within the genetic regions of ELOVL2, MIR29B2CHG, FHL2, KLF14 and TRIM59. We collected 102 blood samples each from donors living in Iraq, Middle East (ME) and Germany, Central Europe (EU). Both sample sets were matched in sex and age ranging from 18 to 68 years with exactly one male and female sample per year of age. All samples were analyzed by bisulfite pyrosequencing applying a multiplex pre-amplification strategy based on a single input of 35 ng converted DNA in the PCR. For the CpGs in MIR29B2CHG, FHL2 and KLF14, we observed significantly different methylation levels between the two populations. While we were able to train two highly accurate prediction models for the respective population with mean absolute deviations between predicted and actual ages (MAD) of 3.34 years for the ME model, and 2.72 years for the EU model, we found an absolute prediction difference between the two population specific models of more than 4 years. A combined model for both populations compensated the methylation difference between the two populations, providing MADs of prediction of only 3.81 years for ME and 3.31 years for EU samples. In total, the results of the present study strongly support the benefit of BGA information for more reliable methylation based age predictions.

A missense mutation in AGTPBP1 was identified in sheep with a lower motor neuron disease.

A type of lower motor neuron (LMN) disease inherited as autosomal recessive in Romney sheep was characterized with normal appearance at birth, but with progressive weakness and tetraparesis after the first week of life. Here, we carried out genome-wide homozygosity mapping using Illumina Ovine SNP50 BeadChips on lambs descended from one carrier ram, including 19 sheep diagnosed as affected and 11 of their parents that were therefore known carriers. A homozygous region of 136 consecutive single-nucleotide polymorphism (SNP) loci on chromosome 2 was common to all affected sheep and it was the basis for searching for the positional candidate genes. Other homozygous regions shared by all affected sheep spanned eight or fewer SNP loci. The 136-SNP region contained the sheep ATP/GTP-binding protein 1 (AGTPBP1) gene. Mutations in this gene have been shown to be related to Purkinje cell degeneration (pcd) phenotypes including ataxia in mice. One missense mutation c.2909G>C on exon 21 of AGTPBP1 was discovered, which induces an Arg to Pro substitution (p.Arg970Pro) at amino-acid 970, a conserved residue for the catalytic activity of AGTPBP1. Genotyping of this mutation showed 100% concordant rate with the recessive pattern of inheritance in affected, carrier, phenotypically normal and unrelated normal individuals. This is the first report showing a mutant AGTPBP1 is associated with a LMN disease in a large mammal animal model. Our finding raises the possibility of human patients with the same etiology caused by this gene or other genes in the same pathway of neuronal development.