Biology subjects

Medugorac, I.

Publications and source records attributed to Medugorac, I..

4 recordsLinked to original sources

bioRxiv2024

Back to the horns: a reconstruction of the ancestral horn state through distinct types of recombination events.

BackgroundBreeding of the genetically polled animals is the desirable approach in modern cattle husbandry. At least four different genetic variants associated with polledness in cattle have been identified, suggesting genetic heterogeneity. These dominant variants have been identified on chromosome 1 between the regions of approx. 2.42 to 2.73 Mb (reference: ARS-UCD1.2), also called the POLLED locus. Among these variants, Friesian (PF, 80 kbp duplication) and Celtic (PC, 212 bp complex InDel) are the most observed in the majority of breeds in the production systems globally, such as in Holstein-Friesian (HF) and Fleckvieh (FV). While a putative causal association of PC with polledness is proven, the presence of large duplication in PF makes it difficult to prove the causality. ResultsIn this study, we conduct whole-genome sequencing (WGS) analysis of two trios exhibiting unexpected inheritance patterns related to PC and PF variants. In both instances, horned offspring were produced from mating pairs where one parent was homozygous for the polled variant, and the other was homozygous for the ancestral horned variant. By analyzing the WGS data generated using long-read sequence technology, we show that de-novo generation of the ancestral horned variant in both the offspring was the result of distinct recombination events. Specifically, in case of the HF trio, it was the result of non-allelic homologous recombination in the gametes of the sire (PF/PF), while in case of the FV trio, it was the result of allelic homologous recombination in the gametes of the dam (PC/PF). The findings from the HF trio support the hypothesis that the 80-kbp duplication is the genetic variant responsible for the polled phenotype of Friesian origin. ConclusionHere we show that different genomic arrangements in POLLED locus can lead to the emergence of de-novo ancestral horn phenotypes. These kinds of arrangements can make a reliable gene test less reliable and the derivation of the phenotype difficult to predict. Therefore, it is important for the large POLLED-locus that any deviation from the expected result is critically analyzed. Possibly some of these cases can further narrow down the sequence motif that is essential for polledness in cattle.

genomics↗

bioRxiv2024

Combined Linkage Disequilibrium and Linkage Analysis (cLDLA): implementation of a powerful approach to identify the genetic basis of complex traits in a bioinformatics workflow.

Identifying the relationship between the polymorphism segregating in a population and phenotypic differences of a trait observed between the individuals of a population is of major biological interest and represents the basis of forward genetics. Much of the traits of interest are influenced by several polymorphic genes and environmental conditions. Often the loci associated with such measurable traits are referred to as Quantitative trait loci. These loci are identified using several statistical approaches. One of them is combined linkage disequilibrium and linkage analysis (cLDLA). This approach, first proposed by Meuwissen and colleagues in 2002, is shown to be robust against population stratification/family structure and requires a relatively lower sample size compared to a genome-wide association study design. Previously, we have successfully used this approach in mapping several important traits in livestock such as identifying the genetic basis of polled condition in cattle and tail length in sheep. A cLDLA requires several complex computation processing and intermediary file conversion steps; for some of these steps no open-source tools are available. Therefore, running this analysis, manually, can prove challenging, tedious, or error-prone. We present, cldla, a bioinformatics workflow implemented in nextflow which takes the vcf file and phenotype file as inputs and implements all the downstream processing required for cLDLA. Additionally, it also has a separate workflow to estimate SNP-based heritability and features for interactive visualization of the results. The workflow is freely available at: https://github.com/Popgen48/cldla.

bioinformatics↗

bioRxiv2021

A scalable, clinically severe pig model for Duchenne muscular dystrophy

Large animal models for Duchenne muscular dystrophy (DMD) are crucial for preclinical evaluation of novel diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMD{Delta}52) resemble molecular, clinical and pathological hallmarks of DMD, but cannot be propagated by breeding due to death before sexual maturity. Therefore, female DMD+/- carriers were generated. A single founder animal had 11 litters with 29 DMDY/-, 34 DMD+/- as well as 36 male and 29 female wild-type (WT) offspring. Breeding with F1 and F2 DMD+/- carriers resulted in additional 114 DMDY/- piglets. The majority of them survived for 3-4 months, providing large cohorts for experimental studies. Pathological investigations and proteome studies of skeletal muscles and myocardium confirmed the resemblance of human disease mechanisms. Importantly, DMDY/- pigs reveal progressive fibrosis of myocardium and increased expression of connexin-43, associated with significantly reduced left ventricular fractional shortening and ejection fraction already at age 3 months. Furthermore, behavioral tests provided evidence for impaired cognitive ability of DMDY/- pigs. Our breeding cohort of DMD{Delta}52 pigs and standardized tissue repositories from DMDY/- pigs, DMD+/- carriers, and WT littermate controls provide important resources for studying DMD disease mechanisms and for testing novel diagnostic procedures and treatment strategies.

pathology↗

bioRxiv2020

Analysis Of Polycerate Mutants Reveals The Evolutionary Co-Option Of HOXD1 To Determine The Number And Topology Of Horns In Bovidae

In the course of evolution, pecorans (i.e. higher ruminants) developed a remarkable diversity of osseous cranial appendages, collectively referred to as headgear, which likely share the same origin and genetic basis. However, the nature and function of the genetic determinants underlying their number and position remain elusive. Jacob and other rare populations of sheep and goats, are characterized by polyceraty, the presence of more than two horns. Here, we characterize distinct POLYCERATE alleles in each species, both associated with defective HOXD1 function. We show that haploinsufficiency at this locus results in the splitting of horn bud primordia, likely following the abnormal extension of an initial morphogenetic field. These results highlight the key role played by this gene in headgear patterning and illustrate the evolutionary co-option of a gene involved in the early development of bilateria to properly fix the position and number of these distinctive organs of Bovidae.

genomics↗