Biology subjects

Matika, O.

Publications and source records attributed to Matika, O..

8 recordsLinked to original sources

bioRxiv2026

A frameshift mutation in PRICKLE1 causes skeletal dysplasia in Cheviot sheep

Skeletal dysplasias can occur in animals, including humans, and are attributed to both environmental and genetic causes. As our understanding of the distinguishing phenotypes of different skeletal dysplasias improves, alongside elucidation of the mechanisms and genetic networks that contribute to skeletal development, identifying and controlling genetic mutations in livestock populations has become increasingly possible, including approaches beyond selective breeding alone. Within Scotland an 'achondroplasia' syndrome that was first described in the South Country Cheviot breed of sheep (OMIA 000004-9940), has continued to occur periodically within the same geographical locations, despite culling of affected lambs over many decades. Affected lambs exhibit rounded heads, short legs, a loss of hooves, abnormal stance and short twisted tails. As the condition has been observed in flocks and as progeny from specific ram and ewe matings, and cases have been co-twinned to normal siblings, this suggests a syndrome caused by a recessive genetic condition rather than environmental factors. Through homozygosity mapping and whole genome sequence analyses, we identified a 10 bp deletion in the open reading frame of the PRICKLE1 gene that encodes prickle planar cell polarity protein 1 and is essential for normal vertebrate embryonic development. We identified additional phenotypes present in affected lambs, including a loss of phalanges, neural tube defects, vertebral and articular chondrocyte defects, hair orientation differences and polycystic kidneys, consistent with a loss of PRICKLE1 function based on comparisons to mouse mutant lines. These findings enabled the development of a simple DNA test for the identified PRICKLE1 mutation that was made commercially available to facilitate the elimination of this genetic disease from sheep flocks.

genetics↗

bioRxiv2025

Genomic selection accuracy and bias using imputed genotypes on growth, welfare and fitness traits in two Pekin duck lines

The current study investigated the genomic selection accuracies and biases estimates from two commercial Pekin duck lines reared under commercial breeding practices. A large dataset of 26K duck records comprising both phenotype and imputed genotype information (60K chip) were analysed for growth, welfare and primary feather length traits. First, we employed mixed linear models with relationship matrices computed from the pedigree (BLUP) or markers (GBLUP) to estimate the variance components and breeding values. Then, we estimated the selection accuracies and selection biases to assess the more appropriate models. Our results showed moderately high imputation accuracies of 0.93 and 0.92 for lines A and D respectively. In both lines, the heritability estimates obtained using the pedigree were generally higher than using genomic markers in all traits considered. These ranged for juvenile weight (JW) from 0.22{+/-}0.01 vs 0.25{+/-}0.01 in line A vs line D using marker information to 0.39{+/-}0.02 to 0.50{+/-}0.02 using the pedigree in line A vs line D for slaughter body weight (BW). We observed very low estimates of heritability for gait 0.07{+/-}0.01 using markers in both lines. Breast muscle depth (BD) also had lower estimates of 0.15-0.16 using markers. For line A, the genomic predictions were generally higher when using the G-matrix than the A-matrix with the highest prediction was for BW (r2=0.68-0.70) and JW with r2 of 0.49. The estimates for gait and foot pad dermatitis (FPD) were greatly improved by using the G-Matrix at 0.58 vs 0.24 and 0.68 vs 0.44 respectively for markers vs pedigree information. For line D, the same improvements for G-Matrix vs A-Matrix were observed with estimates for BD being similar in the two lines. However, for BD the G-Matrix greatly improved the estimates from 0.50 to 0.71 unlike in line A where they remained at 0.50. The bias in line A were minimal (0.01- 0.19) using the G-Matrix compared to 0.02- 0.41 when using A-Matrix. The highest observed bias was for JW followed by BD for the G-matrix whereas when using the A-matrix we observed higher biases in many traits (JW, BW, BD and gait). The biases for line D were generally lower for the G-matrix (0.02 - 0.17 vs 0.00 - 0.19) than those observed in line A using markers whereas higher biases were observed using the pedigree (0.01 - 0.37). Current findings pinpointed that all traits were heritable with higher prediction accuracies and lower biases when using GBLUP as opposed to traditional BLUP. The present study demonstrates the effectiveness of GBLUP for improving prediction accuracy and reducing bias in selection traits of Pekin ducks, particularly for traits with low heritability. Author SummaryThe study explored genomic selection in two commercial Pekin duck lines. Using a large dataset of 26,000 records, including phenotype and genotype data, researchers analyzed growth, welfare, and feather length traits. They applied statistical models to assess variance components and breeding values, comparing traditional pedigree-based methods (BLUP) with genomic marker-based methods (GBLUP). Results showed high imputation accuracies (93% for line A and 92% for line D). Heritability estimates varied, with genomic markers generally producing lower estimates than pedigrees, except for traits like gait and breast muscle depth where genomic predictions were superior. For example, line A showed higher accuracy using genomic data for body weight and juvenile weight. Overall, genomic predictions (GBLUP) provided higher accuracy and lower bias compared to traditional methods, especially for traits with low heritability. This highlights the effectiveness of GBLUP in improving selection processes in Pekin ducks.

genomics↗

bioRxiv2024

Genetic estimates and genome-wide association studies of antibody response in Tanzanian dairy cattle

Identifying the genetic determinants of host defence against infectious pathogens is central to enhancing disease resilience and therapeutic efficacy in livestock. Here we have taken a genome-wide association approach to identify genetic variants associated with the presence of serological markers for important infectious diseases affecting dairy cattle in smallholder farms. Assessing 668,911 single-nucleotide polymorphisms in 1977 crossbreed cattle sampled from six regions of Tanzania, we identified high levels of interregional admixture and European introgression which may increase infectious disease susceptibility relative to indigenous breeds. Heritability estimates ranged from 0.03 (SE {+/-} 0.06) to 0.44 (SE {+/-} 0.07) depending on the pathogen assayed. Preliminary genome scans revealed several loci associated with seropositivity to the viral diseases Rift Valley fever and bovine viral diarrhoea, the protozoan parasites Neospora caninum and Toxoplasma gondii, and the bacterial pathogens Brucella sp, Leptospira hardjo and Coxiella burnetti. The associated loci mapped to genes involved in immune defence, tumour suppression, neurological processes, and cell exocytosis. We discuss future work to clarify the cellular pathways contributing to general and taxon-specific infection responses and to advance selective breeding and therapeutic target designs.

genetics↗

bioRxiv2024

Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping

Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R.A. Fisher, genome-wide association studies (GWAS) extract information using averages and variances from genotype-phenotype datasets. Averages and variances are legitimated upon creating distribution density functions obtained through the grouping of data into categories. However, as data from within a given category cannot be differentiated, the investigative power of such methodologies is limited. Genomic Informational Field Theory (GIFT) is a method specifically designed to circumvent this issue. The way GIFT proceeds is opposite to that of GWAS. Whilst GWAS determines the extent to which genes are involved in phenotype formation (bottom-up approach), GIFT determines the degree to which the phenotype can select microstates (genes) for its subsistence (top-down approach). Doing so requires dealing with new genetic concepts, a.k.a. genetic paths, upon which significance levels for genotype-phenotype associations can be determined. By using different datasets obtained in ovis aries related to bone growth (Dataset-1) and to a series of linked metabolic and epigenetic pathways (Dataset-2), we demonstrate that removing the informational barrier linked to categories enhances the investigative and discriminative powers of GIFT, namely that GIFT extracts more information than GWAS. We conclude by suggesting that GIFT is an adequate tool to study how phenotypic plasticity and genetic assimilation are linked. NEW & NOTEWORTHYThe genetic basis of complex traits remains challenging to investigate using classic GWASs. Given the success of gene editing technologies this point needs to be addressed urgently since there can only be useful editing technologies if precise genotype-phenotype mapping information is available initially. GIFT is a new mapping method designed to increase the investigative power of biological/medical datasets suggesting, in turn, the need to rethink the conceptual bases of quantitative genetics.

genetics↗

bioRxiv2021

A locus conferring tolerance to Theileria infection in African cattle

East Coast fever, a tick-borne cattle disease caused by the Theileria parva parasite, is among the biggest natural killers of cattle in East Africa, leading to over 1 million deaths annually. Here we report on the genetic analysis of a cohort of Boran cattle demonstrating heritable tolerance to infection by T. parva (h2 = 0.65, s.e. 0.57). Through a linkage analysis we identify a 6 Mb genomic region on Bos taurus chromosome 15 that is significantly associated with survival outcome following T. parva exposure. Testing this locus in an independent cohort of animals replicates this association with survival following T. parva infection. A stop gained polymorphism in this region was found to be highly associated with survival across both related and unrelated animals, with only one of the 20 homozygote carriers (T/T) of this change succumbing to the disease in contrast to 44 out of 97 animals homozygote for the reference allele (C/C). Consequently, we present a genetic locus linked to tolerance of one of Africas most important cattle diseases, raising the promise of marker-assisted selection for cattle that are less susceptible to infection by T. parva. Author SummaryMore than a million cattle die of East Coast fever in Africa each year, the impact of which disproportionately falls onto low-income, smallholder farmers. The lack of a widely accessible vaccine, heavy reliance on chemicals to control the tick vector and inadequate drug treatments means that new approaches for controlling the disease are urgently required. Through a genetic study of an extended pedigree of Boran cattle that are more than three times less likely to succumb to the disease than matched controls, we identify a region on chromosome 15 of the cattle genome associated with a high level of tolerance to the disease. We show that a variant in this region is also associated with survival in an independent cohort, and is linked to rates of cell expansion during infection. This genetic variant can therefore support marker-assisted selection, allowing farmers to breed tolerant cattle and offers a route to introduce this beneficial DNA to non-native breeds, enabling reduced disease incidence and increased productivity, which would be of benefit to millions of rural smallholder farmers across Africa.

genetics↗

bioRxiv2018

Balancing selection at a premature stop mutation in the myostatin gene underlies a recessive leg weakness syndrome in pigs

Balancing selection provides a plausible explanation for the maintenance of deleterious alleles at moderate frequency in livestock, including lethal recessives exhibiting heterozygous advantage in carriers. In the current study, a leg weakness syndrome causing mortality of piglets in a commercial line showed monogenic recessive inheritance, and a region on chromosome 15 associated with the syndrome was identified by homozygosity mapping. Whole genome resequencing of cases and controls identified a mutation coding for a premature stop codon within exon 3 of the porcine Myostatin (MSTN) gene, similar to those causing a double-muscling phenotype observed in several mammalian species. The MSTN mutation was in Hardy-Weinberg equilibrium in the population at birth, but significantly distorted amongst animals still in the herd at 110 kg, due to an absence of homozygous mutant genotypes. In heterozygous form, the MSTN mutation was associated with a major increase in muscle depth and decrease in fat depth, suggesting that the deleterious allele was maintained at moderate frequency due to heterozygous advantage. Knockout of the porcine MSTN by gene editing has previously been linked to problems of low piglet survival and lameness. This MSTN mutation is an example of putative balancing selection in livestock, providing a plausible explanation for the lack of disrupting MSTN mutations in pigs despite many generations of selection for lean growth.

genetics↗

bioRxiv2018

Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed.

Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (Canis lupus familiaris), and has been associated with glaucoma and blindness. Goniodysgenesis and early-onset glaucoma initially emerged in Border Collies in Australia in the late 1990s and has subsequently been found in Europe and the USA. The objective of the present study was to determine the genetic basis of goniodysgenesis in Border Collies. Clinical diagnosis was based on results of examinations by veterinary ophthalmologists of affected and unaffected dogs from eleven different countries. Genotyping using the Illumina high density canine SNP chip and whole genome sequencing were used to identify candidate genetic regions. Expression profiles and evolutionary conservation of candidate genes were assessed using public databases. Analysis of pedigree information was consistent with an autosomal recessive mode of inheritance for severe goniodysgenesis (potentially leading to glaucoma) in this breed. There was a highly significant peak of association over chromosome 17, with a p-value of 2 x 10-13. Whole genome sequences of three dogs with glaucoma, three severely affected and three unaffected dogs identified a missense variant in the olfactomedin like 3 (OLFML3) gene in all six affected animals. This was homozygous in all nine cases with glaucoma and 12 of 14 other severely affected animals. Of 67 reportedly unaffected animals, only one (offspring of two homozygous affected parents) was homozygous for this variant. The identification of a candidate genetic region and putative causative mutation will aid breeders to reduce the frequency of goniodysgenesis and the risk of glaucoma in the Border Collie population.

genetics↗

bioRxiv2017

A genome-wide association study for host resistance to Ostreid Herpesvirus in Pacific oysters (Crassostrea gigas)

Ostreid herpesvirus (OsHV) can cause mass mortality events in Pacific oyster aquaculture. While various factors impact on the severity of outbreaks, it is clear that genetic resistance of the host is an important determinant of mortality levels. This raises the possibility of selective breeding strategies to improve the genetic resistance of farmed oyster stocks, thereby contributing to disease control. Traditional selective breeding can be augmented by use of genetic markers, either via marker-assisted or genomic selection. The aim of the current study was to investigate the genetic architecture of resistance to OsHV in Pacific oyster, to identify genomic regions containing putative resistance genes, and to inform the use of genomics to enhance efforts to breed for resistance. To achieve this, a population of ~1,000 juvenile oysters were experimentally challenged with a virulent form of OsHV, with samples taken from mortalities and survivors for genotyping and qPCR measurement of viral load. The samples were genotyped using a recently-developed SNP array, and the genotype data were used to reconstruct the pedigree. Using these pedigree and genotype data, the first high density linkage map was constructed for Pacific oyster, containing 20,353 SNPs mapped to the ten pairs of chromosomes. Genetic parameters for resistance to OsHV were estimated, indicating a significant but low heritability for the binary trait of survival and also for viral load measures (h2 0.12 - 0.25). A genome-wide association study highlighted a region of linkage group 6 containing a significant QTL affecting host resistance. These results are an important step towards identification of genes underlying resistance to OsHV in oyster, and a step towards applying genomic data to enhance selective breeding for disease resistance in oyster aquaculture.

genomics↗