Sequence Variant Analysis of the APOCII Locus among an Arab Cohort.

Apolipoprotein CII (ApocII) plays a key role in regulating lipoprotein lipase (LPL) in lipid metabolism and transport. Numerous polymorphisms within APOCII are reportedly associated with type 2 diabetes mellitus (T2DM), dyslipidemia, and aberrant plasma lipid levels. Few studies have investigated sequence variants at APOCII loci and their association with metabolic disorders. This study aimed to identify and characterize genetic variants by sequencing the full APOCII locus and its flanking sequences in a sample of the Kuwaiti Arab population, including patients with T2DM, hypertriglyceridemia, non-Arab patients with T2DM, and healthy Arab controls. A total of 52 variants were identified in the noncoding sequences: 45 single nucleotide polymorphisms, wherein five were novel, and seven insertion deletions. The minor allele frequency (MAF) of the 47 previously reported variants was similar to the global MAF and to that reported in major populations. Sequence variant analysis predicted a conserved role for APOCII with a potential role for rs5120 in T2DM and rs7133873 as an informative ethnicity marker. This study adds to the ongoing research that attempts to identify ethnicity-specific variants in the apolipoprotein gene loci and associated LPL genes to elucidate the molecular mechanisms of metabolic disorders.

Polymorphisms in MC1R and ASIP Genes are Associated with Coat Color Variation in the Arabian Camel.

Pigmentation in mammals is primarily determined by the distribution of eumelanin and pheomelanin, the ratio of which is mostly controlled by the activity of melanocortin 1 receptor (MC1R) and agouti signaling protein (ASIP) genes. Using 91 animals from 10 Arabian camel populations, that included the 4 predominant coat color phenotypes observed in the dromedary (light brown, dark brown, black, and white), we investigated the effects of the MC1R and ASIP sequence variants and identified candidate polymorphisms associated with coat color variation. In particular, we identified a single nucleotide polymorphism (SNP), found in the coding region of MC1R (901C/T), linked to the white coat color, whereas a 1-bp deletion (23delT/T) and a SNP (25G/A) in exon 2 of ASIP are associated with both black and dark-brown coat colors. Our results also indicate support that the light-brown coat color is likely the ancestral coat color for the dromedary. These sequence variations at the MC1R and ASIP genes represent the first documented evidence of candidate polymorphisms associated with Mendelian traits in the dromedary.

Long-range linkage disequilibrium events on the genome of dromedary camels as a signal of epistatic and directional positive selection.

The genome of dromedary camels has been subjected to various evolutionary forces, such as genetic admixture, natural positive selection, and epistatic selection. These forces are considered as main factors associated with the formation of long-range linkage disequilibrium (LRLD) events. We have analyzed whole-genome data of 56 dromedary camel samples from different geographical regions across the Arabian Peninsula for two main purposes: first, to assess the level of linkage disequilibrium, and second, to identify autosomal LRLD events. The analysis revealed a mean r 2 value of 0.25 (±0.028) over the dromedary autosomes, with a continuous decay until reaching a plateau at inter-variant distances >400 kb. A total of 1847 LRLD events were identified within the dromedary autosomes, which harbor 36 prevalent haplotypes. A level of genetic admixture was observed among the dromedary populations analyzed, which might be a source for the observed LRLD events. Four functional interactions were revealed among the genes found within the LRLD events, with some genes overlapping with prevalent haplotypes, indicative of potential epistatic selection. Genes related to renal function, fertility, thermal regulation, bone structure, and insulin regulation were found among the LRLD genes. These genes, along with the defined prevalent haplotypes, can be considered as hotspots for natural positive selection associated with the LRLD distribution on dromedary genomes. In this study, we have for the first time analyzed the genome of dromedary camels for LRLD events possibly influenced by forces including genetic admixture, epistatic and positive selection. The revealed LRLD elements and prevalent haplotypes should be accounted for when designing breeding programmes to conserve the genetic stock of this well-adapted domestic species.

Signatures of purifying selection and site-specific positive selection on the mitochondrial DNA of dromedary camels (Camelus dromedarius).

The two species of the Old World Camelini tribe, dromedary and Bactrian camels, show superior adaptability to the different environmental conditions they populate, e.g. desert, mountains and coastal areas, which might be associated with adaptive variations on their mitochondrial DNA. Here, we investigate signatures of natural selection in the 13-mitochondrial protein-coding genes of different dromedary camel populations from the Arabian Peninsula, Africa and southwest Asia. The full mitogenome sequences of 42 dromedaries, 38 domestic Bactrian, 29 wild Bactrian camels and 31 samples representing the New World Lamini tribe reveal species-wise genetic distinction among Camelidae family species, with no evidence of geographic distinction among dromedary camels. We observe gene-wide signals of adaptive divergence between the Old World and New World camels, with evidence of purifying selection among Old World camel species. Upon comparing the different Camelidae tribes, 27 amino acid substitutions across ten mtDNA protein-coding genes were found to be under positive selection, in which, 24 codons were defined to be under positive adaptive divergence between Old World and New World camels. Seven codons belonging to three genes demonstrated positive selection in dromedary lineage. A total of 89 codons were found to be under positive selection in Camelidae family based on investigating the impact of amino acid replacement on the physiochemical properties of proteins, including equilibrium constant and surrounding hydrophobicity. These mtDNA variants under positive selection in the Camelidae family might be associated with their adaptation to their contrasting environments.

Assessing genetic diversity and defining signatures of positive selection on the genome of dromedary camels from the southeast of the Arabian Peninsula.

Dromedary camels (Camelus dromedarius) are members of the Camelini tribe within the Camelidae family. They are distributed throughout North Africa, the Arabian Peninsula and Southeast Asia. This domestic species is characterized by its superior adaptability to the harsh desert environment. In this study, whole autosomal data of 29 dromedary samples from the Southeast Arabian Peninsula in Oman; 10 from Muscat, 14 from Al-Batinah, and 5 from Al-Sharqiya, were investigated to assess their genetic relationship and to define candidate signatures of positive selection. A minimal genetic distinction that separates Muscat dromedaries from the other two populations was observed, with a degree of genetic admixture between them. Using the de-correlated composite of multiple signals (DCMS) approach, a total of 47 candidate regions within the autosomes of these dromedary populations were defined with signatures of positive selection. These candidate regions harbor a total of 154 genes that are mainly associated with functional categories related to immune response, lipid metabolism and energy expenditure, optical and auditory functions, and long-term memory. Different functional genomic variants were called on the candidate regions and respective genes that warrant further investigation to find possible association with the different favorable phenotypes in dromedaries. The output of this study paves the way for further research efforts aimed at defining markers for use in genomic breeding programs, with the goal of conserving the genetic diversity of the species and enhancing its productivity.

Homogeneity of Arabian Peninsula dromedary camel populations with signals of geographic distinction based on whole genome sequence data.

Dromedary camels in the Arabian Peninsula distribute along different geographical and ecological locations, e.g. desert, mountains and coasts. Here, we are aiming to explore the whole genome sequence data of ten dromedary populations from the Arabian Peninsula to assess their genetic structure, admixture levels, diversity and similarity indices. Upon including reference dromedary and Bactrian camel populations from Iran and Kazakhstan, we characterise inter-species and geographic genetic distinction between the dromedary and the Bactrian camels. Individual-based alpha genetic diversity profiles are found to be generally higher in Bactrian camels than dromedary populations, with the exception of five autosomes (NC_044525.1, NC_044534.1, NC_044540.1, NC_044542.1, NC_044544.1) at diversity orders (q ≥ 2). The Arabian Peninsula camels are generally homogenous, with a small degree of genetic distinction correlating with three geographic groups: North, Central and West; Southwest; and Southeast of the Arabian Peninsula. No significant variation in diversity or similarity indices are observed among the different Arabian Peninsula dromedary populations. This study contributes to our understanding of the genetic diversity of Arabian Peninsula dromedary camels. It will help conserve the genetic stock of this species and support the design of breeding programmes for genetic improvement of favorable traits.

Genome Diversity and Signatures of Selection for Production and Performance Traits in Dromedary Camels.

Dromedary camels (Camelus dromedarius) are single-humped animals found throughout the deserts of Africa, the Arabian Peninsula, and the southwest of Asia. This well-adapted species is mainly used for milk and meat production, although some specific types exhibit superior running performance and are used in racing competitions. However, neither performance nor production camels are bred under intensive genomic selection programs with specific aims to improve these traits. In this study, the full genome sequence data of six camels from the Arabian Peninsula and the genotyping-by-sequencing data of 44 camels (29 packing and 15 racing) from Sudan were analyzed to assess their genome diversities, relationships, and candidate signatures of positive selection. Genome ADMIXTURE and principle component analyses indicate clear geographic separation between the Sudanese and the Arabian Peninsula camels, but with no population-specific genetic distinction within populations. Camel samples from the Arabian Peninsula show higher mean heterozygosity (0.560 ± 0.003) than those from Sudan (0.347 ± 0.003). Analyses of signatures of selection, using pooled heterozygosity (Hp) approach, in the Sudanese camels revealed 176, 189, and 308 candidate regions under positive selection in the combined and packing and racing camel populations, respectively. These regions host genes that might be associated with adaptation to arid environment, dairy traits, energy homeostasis, and chondrogenesis. Eight regions show high genetic differentiation, based on Fst analysis, between the Sudanese packing and racing camel types. Genes associated with chondrogenesis, energy balance, and urinary system development were found within these regions. Our results advocate for further detailed investigation of the genome of the dromedary camel to identify and characterize genes and variants associated with their valuable phenotypic traits. The results of which may support the development of breeding programs to improve the production and performance traits of this unique domesticated species.

Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia.

Genomic regions subjected to selection frequently show signatures such as within-population reduced nucleotide diversity and outlier values of differentiation among differentially selected populations. In this study, we analyzed 50K SNP genotype data of 373 animals belonging to 23 sheep breeds of different geographic origins using the Rsb (extended haplotype homozygosity) and FST statistical approaches, to identify loci associated with the fat-tail phenotype. We also checked if these putative selection signatures overlapped with regions of high-homozygosity (ROH). The analyses identified novel signals and confirmed the presence of selection signature in genomic regions that harbor candidate genes known to affect fat deposition. Several genomic regions that frequently appeared in ROH were also identified within each breed, but only two ROH islands overlapped with the putative selection signatures. The results reported herein provide the most complete genome-wide study of selection signatures for fat-tail in African and Eurasian sheep breeds; they also contribute insights into the genetic basis for the fat tail phenotype in sheep, and confirm the great complexity of the mechanisms that underlie quantitative traits, such as the fat-tail.

Genomic signatures of adaptive introgression and environmental adaptation in the Sheko cattle of southwest Ethiopia.

Although classified as an African taurine breed, the genomes of Sheko cattle are an admixture of Asian zebu and African taurine ancestries. They populate the humid Bench Maji zone in Sheko and Bench districts in the south-western part of Ethiopia and are considered as a trypanotolerant breed with high potential for dairy production. Here, we investigate the genome of Sheko cattle for candidate signatures of adaptive introgression and positive selection using medium density genome-wide SNP data. Following locus-ancestry deviation analysis, 15 and 72 genome regions show substantial excess and deficiency in Asian zebu ancestry, respectively. Nine and 23 regions show candidate signatures of positive selection following extended haplotype homozygosity (EHH)-based analyses (iHS and Rsb), respectively. The results support natural selection before admixture for one iHS, one Rsb and three zebu ancestry-deficient regions. Genes and/or QTL associated with bovine immunity, fertility, heat tolerance, trypanotolerance and lactation are present within candidate selected regions. The identification of candidate regions under selection in Sheko cattle warrants further investigation of a larger sample size using full genome sequence data to better characterise the underlying haplotypes. The results can then support informative genomic breeding programmes to sustainably enhance livestock productivity in East African trypanosomosis infested areas.

Signatures of positive selection in African Butana and Kenana dairy zebu cattle.

Butana and Kenana are two types of zebu cattle found in Sudan. They are unique amongst African indigenous zebu cattle because of their high milk production. Aiming to understand their genome structure, we genotyped 25 individuals from each breed using the Illumina BovineHD Genotyping BeadChip. Genetic structure analysis shows that both breeds have an admixed genome composed of an even proportion of indicine (0.75 ± 0.03 in Butana, 0.76 ± 0.006 in Kenana) and taurine (0.23 ± 0.009 in Butana, 0.24 ± 0.006 in Kenana) ancestries. We also observe a proportion of 0.02 to 0.12 of European taurine ancestry in ten individuals of Butana that were sampled from cattle herds in Tamboul area suggesting local crossbreeding with exotic breeds. Signatures of selection analyses (iHS and Rsb) reveal 87 and 61 candidate positive selection regions in Butana and Kenana, respectively. These regions span genes and quantitative trait loci (QTL) associated with biological pathways that are important for adaptation to marginal environments (e.g., immunity, reproduction and heat tolerance). Trypanotolerance QTL are intersecting candidate regions in Kenana cattle indicating selection pressure acting on them, which might be associated with an unexplored level of trypanotolerance in this cattle breed. Several dairy traits QTL are overlapping the identified candidate regions in these two zebu cattle breeds. Our findings underline the potential to improve dairy production in the semi-arid pastoral areas of Africa through breeding improvement strategy of indigenous local breeds.

Genome-Wide Variation, Candidate Regions and Genes Associated With Fat Deposition and Tail Morphology in Ethiopian Indigenous Sheep.

Variations in body weight and in the distribution of body fat are associated with feed availability, thermoregulation, and energy reserve. Ethiopia is characterized by distinct agro-ecological and human ethnic farmer diversity of ancient origin, which have impacted on the variation of its indigenous livestock. Here, we investigate autosomal genome-wide profiles of 11 Ethiopian indigenous sheep populations using the Illumina Ovine 50 K SNP BeadChip assay. Sheep from the Caribbean, Europe, Middle East, China, and western, northern and southern Africa were included to address globally, the genetic variation and history of Ethiopian populations. Population relationship and structure analysis separated Ethiopian indigenous fat-tail sheep from their North African and Middle Eastern counterparts. It indicates two main genetic backgrounds and supports two distinct genetic histories for African fat-tail sheep. Within Ethiopian sheep, our results show that the short fat-tail sheep do not represent a monophyletic group. Four genetic backgrounds are present in Ethiopian indigenous sheep but at different proportions among the fat-rump and the long fat-tail sheep from western and southern Ethiopia. The Ethiopian fat-rump sheep share a genetic background with Sudanese thin-tail sheep. Genome-wide selection signature analysis identified eight putative candidate regions spanning genes influencing growth traits and fat deposition (NPR2, HINT2, SPAG8, INSR), development of limbs and skeleton, and tail formation (ALX4, HOXB13, BMP4), embryonic development of tendons, bones and cartilages (EYA2, SULF2), regulation of body temperature (TRPM8), body weight and height variation (DIS3L2), control of lipogenesis and intracellular transport of long-chain fatty acids (FABP3), the occurrence and morphology of horns (RXFP2), and response to heat stress (DNAJC18). Our findings suggest that Ethiopian fat-tail sheep represent a uniquely admixed but distinct genepool that presents an important resource for understanding the genetic control of skeletal growth, fat metabolism and associated physiological processes.

Signatures of Selection for Environmental Adaptation and Zebu × Taurine Hybrid Fitness in East African Shorthorn Zebu.

The East African Shorthorn Zebu (EASZ) cattle are ancient hybrid between Asian zebu × African taurine cattle preferred by local farmers due to their adaptability to the African environment. The genetic controls of these adaptabilities are not clearly understood yet. Here, we genotyped 92 EASZ samples from Kenya (KEASZ) with more than 770,000 SNPs and sequenced the genome of a pool of 10 KEASZ. We observe an even admixed autosomal zebu × taurine genomic structure in the population. A total of 101 and 165 candidate regions of positive selection, based on genome-wide SNP analyses (meta-SS, Rsb, iHS, and ΔAF) and pooled heterozygosity (Hp) full genome sequence analysis, are identified, in which 35 regions are shared between them. A total of 142 functional variants, one novel, have been detected within these regions, in which 30 and 26 were classified as of zebu and African taurine origins, respectively. High density genome-wide SNP analysis of zebu × taurine admixed cattle populations from Uganda and Nigeria show that 25 of these regions are shared between KEASZ and Uganda cattle, and seven regions are shared across the KEASZ, Uganda, and Nigeria cattle. The identification of common candidate regions allows us to fine map 18 regions. These regions intersect with genes and QTL associated with reproduction and environmental stress (e.g., immunity and heat stress) suggesting that the genome of the zebu × taurine admixed cattle has been uniquely selected to maximize hybrid fitness both in terms of reproduction and survivability.

Polycythemia vera presenting as acute myocardial infarction: An unusual presentation.

Acute myocardial infarction (AMI) is usually seen in the setting of atherosclerosis and its associated risk factors. Myocardial infarction in the young poses a particular challenge, as the disease is less likely, due to atherosclerosis. We report the case of a 37-year-old female patient who presented with ST segment elevation anterolateral AMI. The only abnormality on routine blood investigation was raised hemoglobin and hematocrit. After further testing, she was diagnosed according to the World Health Organization (WHO) criteria with polycythemia vera. This case illustrates the importance of recognizing polycythemia vera as an important cause of thrombosis, which can present initially as AMI, and to emphasize the early recognition of the disease in order to initiate appropriate management strategies.

Signatures of positive selection in East African Shorthorn Zebu: A genome-wide single nucleotide polymorphism analysis.

The small East African Shorthorn Zebu (EASZ) is the main indigenous cattle across East Africa. A recent genome wide SNP analysis revealed an ancient stable African taurine x Asian zebu admixture. Here, we assess the presence of candidate signatures of positive selection in their genome, with the aim to provide qualitative insights about the corresponding selective pressures. Four hundred and twenty-five EASZ and four reference populations (Holstein-Friesian, Jersey, N'Dama and Nellore) were analysed using 46,171 SNPs covering all autosomes and the X chromosome. Following FST and two extended haplotype homozygosity-based (iHS and Rsb) analyses 24 candidate genome regions within 14 autosomes and the X chromosome were revealed, in which 18 and 4 were previously identified in tropical-adapted and commercial breeds, respectively. These regions overlap with 340 bovine QTL. They include 409 annotated genes, in which 37 were considered as candidates. These genes are involved in various biological pathways (e.g. immunity, reproduction, development and heat tolerance). Our results support that different selection pressures (e.g. environmental constraints, human selection, genome admixture constrains) have shaped the genome of EASZ. We argue that these candidate regions represent genome landmarks to be maintained in breeding programs aiming to improve sustainable livestock productivity in the tropics.

Umbilical cord blood stem cells - potential therapeutic tool for neural injuries and disorders.

Brain limited self-renewal capability is the main element behind the seriousness of neurodegenerative diseases and neural injuries. Any possible attempts to use cell replacement-therapy approaches rely on: first, the ability of such cells to generate neural cells and tissues with developmental and functional similarities to human brain cells and second, development of safe and effective protocols for cells transplantations. Many recent studies showed that human umbilical cord blood stem cells have the potential to generate cells with neuronal characteristics. It has also been shown that these stem cells have a positive impact on animal models of neural injuries and diseases. Umbilical cord blood stem cells are a potential candidate for clinical therapies for neural injuries and neural degenerative diseases for which current mode of therapy is inadequate. In addition, they might provide an in-vitro model of parenchymal neural cells for toxicology and drugs testing research.