The centromere is the chromosomal locus essential for proper chromosome segregation. While the centromeric function is well conserved and epigenetically specified, centromeric DNA sequences are typically composed of satellite DNA and represent the most rapidly evolving sequences in eukaryotic genomes. The presence of satellite sequences at centromeres hampered the comprehensive molecular analysis of these enigmatic loci. The discovery of functional centromeres completely devoid of satellite repetitions and fixed in some animal and plant species represented a turning point in centromere biology, definitively proving the epigenetic nature of the centromere. The first satellite-free centromere, fixed in a vertebrate species, was discovered in the horse. Later, an extraordinary number of satellite-free neocentromeres had been discovered in other species of the genus Equus, which remains the only mammalian genus with numerous satellite-free centromeres described thus far. These neocentromeres arose recently during evolution and are caught in a stage of incomplete maturation. Their presence made the equids a unique model for investigating, at molecular level, the minimal requirements for centromere seeding and evolution. This model system provided new insights on how centromeres are established and transmitted to the progeny and on the role of satellite DNA in different aspects of centromere biology.

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Molecular Dynamics and Evolution of Centromeres in the Genus Equus

Abstract Background Increases in serum gamma‐glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. Hypothesis/Objectives Classify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs. Animals A total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity <40 IU/L). Lipase: n = 19 affected, n = 35 control. Serum α‐tocopherol concentrations: n = 32 affected, n = 46 control. Genome‐wide association study (GWAS): 36 affected, 58 control. Whole genome sequencing: n = 5 affected, n = 5 control. Methods Biochemical and vitamin analytes were compared among cohorts. A GWAS was performed and a subset of TBs underwent whole genome sequencing to interrogate candidate genes and positional genetic regions. Results Serum lipase and amylase activity and α‐tocopherol concentrations did not differ between groups. No genetic variants were identified in 2 candidate genes (UGT1A1 and GGT1) that associated with the phenotype. Four single nucleotide polymorphisms (SNPs) approached a suggestive association with the phenotype (P = 2.15 × 10−5), defining a 100 kb region on chromosome 5 surrounding cluster of differentiation 1a (CD1A1), a transmembrane gene related to the major histocompatibility complex. Conclusions and Clinical Importance An underlying genetic etiology may exist for high GGT syndrome in racing TBs, similar to genetic disorders in humans.

Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorses

In mammals, centromeres are epigenetically specified by the histone H3 variant CENP-A and are typically associated with satellite DNA. We previously described the first example of a natural satellite-free centromere on Equus caballus chromosome 11 (ECA11) and, subsequently, on several chromosomes in other species of the genus Equus. We discovered that these satellite-free neocentromeres arose recently during evolution through centromere repositioning and/or chromosomal fusion, after inactivation of the ancestral centromere, where, in many cases, blocks of satellite sequences were maintained. Here, we investigated by FISH the chromosomal distribution of satellite DNA families in Equus przewalskii (EPR), demonstrating a good degree of conservation of the localization of the major horse satellite families 37cen and 2PI with the domestic horse. Moreover, we demonstrated, by ChIP-seq, that 37cen is the satellite bound by CENP-A and that the centromere of EPR10, the ortholog of ECA11, is devoid of satellite sequences. Our results confirm that these two species are closely related and that the event of centromere repositioning which gave rise to EPR10/ECA11 centromeres occurred in the common ancestor, before the separation of the two horse lineages.

/pdf/a-satellite-free-centromere-in-equus-przewalskii-chromosome-1klsyuup.pdf

A Satellite-Free Centromere in Equus przewalskii Chromosome 10

Science-in-brief: Genomic and transcriptomic approaches to the investigation of equine diseases.

Lipids consumed with milk derivatives are one of the main parts of the human diet. Trans fatty acids in milk are causing a debate about their impact on the incidence of cardiovascular disease, pathological abnormalities, and cancer. The fatty acid profile of milk is influenced by a large number of different factors, one of which is genetic. The development of genetic studies, including Genome-Wide Association Studies (GWAS), may help define genomic regions associated with fatty acid content in milk, including trans fatty acids. This article provides an overview of international studies on the identification of genomic regions and SNPs associated with the trans fatty acids in cow’s milk. The results are based on research of cattle such as Norwegian Red cattle, Holstein, Jersey, and Brown Swiss. The presented review shows that 68 SNPs were localized on chromosomes 1, 2, 4–6, 8–10, 12, 14–20, 22–25, and 27–29. Further research in this direction will provide new information that will serve as an impetus for the creation of modern breeding technologies and increase the performance of the manufacture of high-quality dairy products. The search for genetic markers associated with the content of TFA in milk is a promising direction in agricultural science and will allow more complete breeding work with cattle.

https://www.mdpi.com/2077-0472/13/6/1151/pdf?version=1685435110

Overview of SNPs Associated with Trans Fat Content in Cow’s Milk

The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data from more than 400 experiments using over 50 tissues, targeting a variety of regulatory features of the equine genome. In this review, we examine how valuable lessons learned from the ENCODE project informed our decisions in the equine FAANG project. We report the current state of the equine FAANG project and discuss how FAANG can serve as a template for future expansion of functional annotation in the equine genome and be used as a reference for studies of complex traits in horse. A well-annotated reference functional atlas will also help advance equine genetics in the pan-genome and precision medicine era.

Decoding the Equine Genome: Lessons from ENCODE.

https://academic.oup.com/tas/article-pdf/5/Supplement_S1/S1/41388258/txab171.pdf

Alexa M. Barber

Papers

Decoding the Equine Genome: Lessons from ENCODE.

Whole-genome sequencing to investigate a possible genetic basis of perosomus elumbis in a calf resulting from a consanguineous mating