Gene-Set Enrichment Analysis for Identifying Genes and Biological Activities Associated with Growth Traits in Dromedaries

Simple Summary This project aimed to find biological themes affecting growth in dromedaries. Candidate SNPs associated with growth were mapped to 22 genes, and 25 significant themes were identified related to growth. The main biological functions included calcium ion binding, protein binding, DNA-binding transcription factor activity, protein kinase activity, tropomyosin binding, myosin complex, actin-binding, ATP binding, receptor signaling pathway via JAK-STAT, and cytokine activity. EFCAB5, MTIF2, MYO3A, TBX15, IFNL3, PREX1, and TMOD3 genes are candidates for improving growth in camel breeding programs. Growth is an important heritable economic trait for dromedaries and necessary for planning a successful breeding program. Until now, genome-wide association studies (GWAS) and QTL-mapping have identified significant single nucleotide polymorphisms (SNPs) associated with growth in domestic animals, but in dromedaries, the number of studies is very low. This project aimed to find biological themes affecting growth in dromedaries. In the first step, 99 candidate SNPs were chosen from a previously established set of SNPs associated with body weight, gain, and birth weight in Iranian dromedaries. Next, 0.5 kb upstream and downstream of each candidate SNP were selected from NCBI (assembly accession: GCA_000803125.3). The annotation of fragments with candidate SNPs regarding the reference genome was retrieved using the Blast2GO tool. Candidate SNPs associated with growth were mapped to 22 genes, and 25 significant biological themes were identified to be related to growth in dromedaries. The main biological functions included calcium ion binding, protein binding, DNA-binding transcription factor activity, protein kinase activity, tropomyosin binding, myosin complex, actin-binding, ATP binding, receptor signaling pathway via JAK-STAT, and cytokine activity. EFCAB5, MTIF2, MYO3A, TBX15, IFNL3, PREX1, and TMOD3 genes are candidates for improving growth in camel breeding programs

Genomic signatures of domestication in Old World camels

Domestication begins with the selection of animals showing less fear of humans. In most domesticates, selection signals for tameness have been superimposed by intensive breeding for economical or other desirable traits. Old World camels, conversely, have maintained high genetic variation and lack secondary bottlenecks associated with breed development. By re-sequencing multiple genomes from dromedaries, Bactrian camels, and their endangered wild relatives, here we show that positive selection for candidate genes underlying traits collectively referred to as 'domestication syndrome' is consistent with neural crest deficiencies and altered thyroid hormone-based signaling. Comparing our results with other domestic species, we postulate that the core set of domestication genes is considerably smaller than the pan-domestication set - and overlapping genes are likely a result of chance and redundancy. These results, along with the extensive genomic resources provided, are an important contribution to understanding the evolutionary history of camels and the genomic features of their domestication. Robert R. Fitak et al. investigate the genetic basis for domestication in camels. They found that the positive selection of candidate domestication genes is consistent with neural crest deficiencies and altered thyroid hormone-based signaling. Their work provides insights to the evolutionary history of camels and genetics of domestication.Peer reviewe

What's in a name? Common name misuse potentially confounds the conservation of the wild camel Camelus ferus

Common names allow species diversity to be acknowledged by experts and non-specialists alike; they are descriptors with both scientific and cultural implications. However, a lack of clarity when using a common name could risk altering perceptions of threatened species. This is the case for the Critically Endangered wild camel Camelus ferus, which, despite extensive evidence of its species status, is frequently referred to in English as wild Bactrian camel. However, the wild camel (Mongolian: хавтгай, khavtgai; Chinese: 野骆驼, ye luo tuo) is not a wild version of the domestic Bactrian camel Camelus bactrianus but a separate species near extinction, with an estimated population of c. 950. Failure to clearly separate Bactrian and wild camels in name risks masking the plight of the few remaining wild camels with the visible abundance of the domesticated species. Here we advocate the use of the accurate English common name wild camel for C. ferus ideally alongside its Indigenous names to correctly represent its cultural and conservation importance

Genomic prediction for growth using a low-density SNP panel in dromedary camels

For thousands of years, camels have produced meat, milk, and fiber in harsh desert conditions. For a sustainable development to provide protein resources from desert areas, it is necessary to pay attention to genetic improvement in camel breeding. By using genotyping-by-sequencing (GBS) method we produced over 14,500 genome wide markers to conduct a genome- wide association study (GWAS) for investigating the birth weight, daily gain, and body weight of 96 dromedaries in the Iranian central desert. A total of 99 SNPs were associated with birth weight, daily gain, and body weight (p-value \u3c 0.002). Genomic breeding values (GEBVs) were estimated with the BGLR package using (i) all 14,522 SNPs and (ii) the 99 SNPs by GWAS. Twenty-eight SNPs were associated with birth weight, daily gain, and body weight (p-value \u3c 0.001). Annotation of the genomic region (s) within ± 100 kb of the associated SNPs facilitated prediction of 36 candidate genes. The accuracy of GEBVs was more than 0.65 based on all 14,522 SNPs, but the regression coefficients for birth weight, daily gain, and body weight were 0.39, 0.20, and 0.23, respectively. Because of low sample size, the GEBVs were predicted using the associated SNPs from GWAS. The accuracy of GEBVs based on the 99 associated SNPs was 0.62, 0.82, and 0.57 for birth weight, daily gain, and body weight. This report is the first GWAS using GBS on dromedary camels and identifies markers associated with growth traits that could help to plan breeding program to genetic improvement. Further researches using larger sample size and collaboration of the camel farmers and more profound understanding will permit verification of the associated SNPs identified in this project. The preliminary results of study show that genomic selection could be the appropriate way to genetic improvement of body weight in dromedary camels, which is challenging due to a long generation interval, seasonal reproduction, and lack of records and pedigrees

Genomic prediction for growth using a low-density SNP panel in dromedary camels

For thousands of years, camels have produced meat, milk, and fiber in harsh desert conditions. For a sustainable development to provide protein resources from desert areas, it is necessary to pay attention to genetic improvement in camel breeding. By using genotyping-by-sequencing (GBS) method we produced over 14,500 genome wide markers to conduct a genome- wide association study (GWAS) for investigating the birth weight, daily gain, and body weight of 96 dromedaries in the Iranian central desert. A total of 99 SNPs were associated with birth weight, daily gain, and body weight (p-value \u3c 0.002). Genomic breeding values (GEBVs) were estimated with the BGLR package using (i) all 14,522 SNPs and (ii) the 99 SNPs by GWAS. Twenty-eight SNPs were associated with birth weight, daily gain, and body weight (p-value \u3c 0.001). Annotation of the genomic region (s) within ± 100 kb of the associated SNPs facilitated prediction of 36 candidate genes. The accuracy of GEBVs was more than 0.65 based on all 14,522 SNPs, but the regression coefficients for birth weight, daily gain, and body weight were 0.39, 0.20, and 0.23, respectively. Because of low sample size, the GEBVs were predicted using the associated SNPs from GWAS. The accuracy of GEBVs based on the 99 associated SNPs was 0.62, 0.82, and 0.57 for birth weight, daily gain, and body weight. This report is the first GWAS using GBS on dromedary camels and identifies markers associated with growth traits that could help to plan breeding program to genetic improvement. Further researches using larger sample size and collaboration of the camel farmers and more profound understanding will permit verification of the associated SNPs identified in this project. The preliminary results of study show that genomic selection could be the appropriate way to genetic improvement of body weight in dromedary camels, which is challenging due to a long generation interval, seasonal reproduction, and lack of records and pedigrees

Landscape genomics of a widely distributed snake, Dolichophis caspius (Gmelin, 1789) across Eastern Europe and Western Asia

Across the distribution of the Caspian whipsnake (Dolichophis caspius), populations have become increasingly disconnected due to habitat alteration. To understand population dynamics and this widespread but locally endangered snake’s adaptive potential, we investigated population structure, admixture, and effective migration patterns. We took a landscape-genomic approach to identify selected genotypes associated with environmental variables relevant to D. caspius. With double-digest restriction-site associated DNA (ddRAD) sequencing of 53 samples resulting in 17,518 single nucleotide polymorphisms (SNPs), we identified 8 clusters within D. caspius reflecting complex evolutionary patterns of the species. Estimated Effective Migration Surfaces (EEMS) revealed higher-than-average gene flow in most of the Balkan Peninsula and lower-than-average gene flow along the middle section of the Danube River. Landscape genomic analysis identified 751 selected genotypes correlated with 7 climatic variables. Isothermality correlated with the highest number of selected genotypes (478) located in 41 genes, followed by annual range (127) and annual mean temperature (87). We conclude that environmental variables, especially the day-to-night temperature oscillation in comparison to the summer-to-winter oscillation, may have an important role in the distribution and adaptation of D. caspius

Genomic Analyses Show Extremely Perilous Conservation Status of African and Asiatic cheetahs (Acinonyx jubatus).

We live in a world characterized by biodiversity loss and global environmental change. The extinction of large carnivores can have ramifying effects on ecosystems like an uncontrolled increase in wild herbivores, which in turn can have knock-on impacts on vegetation regeneration and communities. Cheetahs (Acinonyx jubatus) serve important ecosystem functions as apex predators; yet, they are quickly heading towards an uncertain future. Threatened by habitat loss, human-wildlife conflict and illegal trafficking, there are only approximately 7100 individuals remaining in nature. We present the most comprehensive genome-wide analysis of cheetah phylogeography and conservation genomics to date, assembling samples from nearly the entire current and past species' range. We show that their phylogeography is more complex than previously thought, and that East African cheetahs (A. j. raineyi) are genetically distinct from Southern African individuals (A. j. jubatus), warranting their recognition as a distinct subspecies. We found strong genetic differentiation between all classically recognized subspecies, thus refuting earlier findings that cheetahs show only little differentiation. The strongest differentiation was observed between the Asiatic and all the African subspecies. We detected high inbreeding in the Critically Endangered Iranian (A. j. venaticus) and North-western (A. j. hecki) subspecies, and show that overall cheetahs, along with snow leopards, have the lowest genome-wide heterozygosity of all the big cats. This further emphasizes the cheetah's perilous conservation status. Our results provide novel and important information on cheetah phylogeography that can support evidence-based conservation policy decisions to help protect this species. This is especially relevant in light of ongoing and proposed translocations across subspecies boundaries, and the increasing threats of illegal trafficking

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters