Whole-genome sequencing reveals a complex African population demographic history and signatures of local adaptation.

We conduct high coverage (>30×) whole-genome sequencing of 180 individuals from 12 indigenous African populations. We identify millions of unreported variants, many predicted to be functionally important. We observe that the ancestors of southern African San and central African rainforest hunter-gatherers (RHG) diverged from other populations >200 kya and maintained a large effective population size. We observe evidence for ancient population structure in Africa and for multiple introgression events from "ghost" populations with highly diverged genetic lineages. Although currently geographically isolated, we observe evidence for gene flow between eastern and southern Khoesan-speaking hunter-gatherer populations lasting until ∼12 kya. We identify signatures of local adaptation for traits related to skin color, immune response, height, and metabolic processes. We identify a positively selected variant in the lightly pigmented San that influences pigmentation in vitro by regulating the enhancer activity and gene expression of PDPK1.

Association between telomere length and Plasmodium falciparum malaria endemicity in sub-Saharan Africans.

Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.

Impact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection.

Human genomic diversity has been shaped by both ancient and ongoing challenges from viruses. The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on population health. However, genetic diversity and evolutionary forces impacting host genes related to SARS-CoV-2 infection are not well understood. We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (angiotensin converting enzyme 2 [ACE2], transmembrane protease serine 2 [TMPRSS2], dipeptidyl peptidase 4 [DPP4], and lymphocyte antigen 6 complex locus E [LY6E]). We analyzed data from 2,012 ethnically diverse Africans and 15,977 individuals of European and African ancestry with electronic health records and integrated with global data from the 1000 Genomes Project. At ACE2, we identified 41 nonsynonymous variants that were rare in most populations, several of which impact protein function. However, three nonsynonymous variants (rs138390800, rs147311723, and rs145437639) were common among central African hunter-gatherers from Cameroon (minor allele frequency 0.083 to 0.164) and are on haplotypes that exhibit signatures of positive selection. We identify signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage compared with the chimpanzee genome. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19. Our study provides insights into global variation at host genes related to SARS-CoV-2 infection, which have been shaped by natural selection in some populations, possibly due to prior viral infections.

Signatures of Convergent Evolution and Natural Selection at the Alcohol Dehydrogenase Gene Region are Correlated with Agriculture in Ethnically Diverse Africans.

The alcohol dehydrogenase (ADH) family of genes encodes enzymes that catalyze the metabolism of ethanol into acetaldehyde. Nucleotide variation in ADH genes can affect the catalytic properties of these enzymes and is associated with a variety of traits, including alcoholism and cancer. Some ADH variants, including the ADH1B*48His (rs1229984) mutation in the ADH1B gene, reduce the risk of alcoholism and are under positive selection in multiple human populations. The advent of Neolithic agriculture and associated increase in fermented foods and beverages is hypothesized to have been a selective force acting on such variants. However, this hypothesis has not been tested in populations outside of Asia. Here, we use genome-wide selection scans to show that the ADH gene region is enriched for variants showing strong signals of positive selection in multiple Afroasiatic-speaking, agriculturalist populations from Ethiopia, and that this signal is unique among sub-Saharan Africans. We also observe strong selection signals at putatively functional variants in nearby lipid metabolism genes, which may influence evolutionary dynamics at the ADH region. Finally, we show that haplotypes carrying these selected variants were introduced into Northeast Africa from a West-Eurasian source within the last ∼2,000 years and experienced positive selection following admixture. These selection signals are not evident in nearby, genetically similar populations that practice hunting/gathering or pastoralist subsistence lifestyles, supporting the hypothesis that the emergence of agriculture shapes patterns of selection at ADH genes. Together, these results enhance our understanding of how adaptations to diverse environments and diets have influenced the African genomic landscape.

Genetics and geography of leukocyte telomere length in sub-Saharan Africans.

Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African-Americans (AAms) and 2464 European-Americans (EAms). LTL differed significantly across SSAs (P = 0.003), with the San from Botswana (with the oldest genomic ancestry) having the longest LTL and populations from Ethiopia having the shortest LTL. SSAs had significantly longer LTL than AAms [P = 6.5(e-16)] whose LTL was significantly longer than EAms [P = 2.5(e-7)]. Genetic variation in SSAs explained 52% of LTL variance versus 27% in AAms and 34% in EAms. Adjustment for genetic variation removed the LTL differences among SSAs. LTL genetic variation among SSAs, with the longest LTL in the San, supports the hypothesis that longer LTL was ancestral in humans. Identifying factors driving LTL variation in Africa may have important ramifications for LTL-associated diseases.

Redondovirus Diversity and Evolution on Global, Individual, and Molecular Scales.

Redondoviridae is a newly established family of circular Rep-encoding single-stranded (CRESS) DNA viruses found in the human ororespiratory tract. Redondoviruses were previously found in ∼15% of respiratory specimens from U.S. urban subjects; levels were elevated in individuals with periodontitis or critical illness. Here, we report higher redondovirus prevalence in saliva samples: four rural African populations showed 61 to 82% prevalence, and an urban U.S. population showed 32% prevalence. Longitudinal, limiting-dilution single-genome sequencing revealed diverse strains of both redondovirus species (Brisavirus and Vientovirus) in single individuals, persistence over time, and evidence of intergenomic recombination. Computational analysis of viral genomes identified a recombination hot spot associated with a conserved potential DNA stem-loop structure. To assess the possible role of this site in recombination, we carried out in vitro studies which showed that this potential stem-loop was cleaved by the virus-encoded Rep protein. In addition, in reconstructed reactions, a Rep-DNA covalent intermediate was shown to mediate DNA strand transfer at this site. Thus, redondoviruses are highly prevalent in humans, found in individuals on multiple continents, heterogeneous even within individuals and encode a Rep protein implicated in facilitating recombination. IMPORTANCERedondoviridae is a recently established family of DNA viruses predominantly found in the human respiratory tract and associated with multiple clinical conditions. In this study, we found high redondovirus prevalence in saliva from urban North American individuals and nonindustrialized African populations in Botswana, Cameroon, Ethiopia, and Tanzania. Individuals on both continents harbored both known redondovirus species. Global prevalence of both species suggests that redondoviruses have long been associated with humans but have remained undetected until recently due to their divergent genomes. By sequencing single redondovirus genomes in longitudinally sampled humans, we found that redondoviruses persisted over time within subjects and likely evolve by recombination. The Rep protein encoded by redondoviruses catalyzes multiple reactions in vitro, consistent with a role in mediating DNA replication and recombination. In summary, we identify high redondovirus prevalence in humans across multiple continents, longitudinal heterogeneity and persistence, and potential mechanisms of redondovirus evolution by recombination.

Genomic evidence for shared common ancestry of East African hunting-gathering populations and insights into local adaptation.

Anatomically modern humans arose in Africa ∼300,000 years ago, but the demographic and adaptive histories of African populations are not well-characterized. Here, we have generated a genome-wide dataset from 840 Africans, residing in western, eastern, southern, and northern Africa, belonging to 50 ethnicities, and speaking languages belonging to four language families. In addition to agriculturalists and pastoralists, our study includes 16 populations that practice, or until recently have practiced, a hunting-gathering (HG) lifestyle. We observe that genetic structure in Africa is broadly correlated not only with geography, but to a lesser extent, with linguistic affiliation and subsistence strategy. Four East African HG (EHG) populations that are geographically distant from each other show evidence of common ancestry: the Hadza and Sandawe in Tanzania, who speak languages with clicks classified as Khoisan; the Dahalo in Kenya, whose language has remnant clicks; and the Sabue in Ethiopia, who speak an unclassified language. Additionally, we observed common ancestry between central African rainforest HGs and southern African San, the latter of whom speak languages with clicks classified as Khoisan. With the exception of the EHG, central African rainforest HGs, and San, other HG groups in Africa appear genetically similar to neighboring agriculturalist or pastoralist populations. We additionally demonstrate that infectious disease, immune response, and diet have played important roles in the adaptive landscape of African history. However, while the broad biological processes involved in recent human adaptation in Africa are often consistent across populations, the specific loci affected by selective pressures more often vary across populations.

Population differentiated copy number variation of Bos taurus, Bos indicus and their African hybrids.

BACKGROUND: CNV comprises a large proportion in cattle genome and is associated with various traits. However, there were few population-scale comparison studies on cattle CNV. RESULTS: Here, autosome-wide CNVs were called by read depth of NGS alignment result and copy number variation regions (CNVRs) defined from 102 Eurasian taurine (EAT) of 14 breeds, 28 Asian indicine (ASI) of 6 breeds, 22 African taurine (AFT) of 2 breeds, and 184 African humped cattle (AFH) of 17 breeds. The copy number of every CNVRs were compared between populations and CNVRs with population differentiated copy numbers were sorted out using the pairwise statistics VST and Kruskal-Wallis test. Three hundred sixty-two of CNVRs were significantly differentiated in both statistics and 313 genes were located on the population differentiated CNVRs. CONCLUSION: For some of these genes, the averages of copy numbers were also different between populations and these may be candidate genes under selection. These include olfactory receptors, pathogen-resistance, parasite-resistance, heat tolerance and productivity related genes. Furthermore, breed- and individual-level comparison was performed using the presence or copy number of the autosomal CNVRs. Our findings were based on identification of CNVs from short Illumina reads of 336 individuals and 39 breeds, which to our knowledge is the largest dataset for this type of analysis and revealed important CNVs that may play a role in cattle adaption to various environments.

Multivariate characterization of phenotypic traits of five native cattle populations from Tigray, Northern Ethiopia.

Abergelle, Arado, Begait, Irob, and Raya are important native cattle populations that are well adapted to the harsh natural conditions in Tigray, Ethiopia. However, little is known about their phenotypic characteristics and inter-population variability. Understanding the phenotypic characteristics is the crucial step in an effort of maintaining genetic diversity and conserving important traits for adaptation. A total of 1650 native matured cattle from the five populations were used to investigate the phenotypic characteristics and variability based on 21 qualitative traits and 21 body measurements using uni- and multivariate, and discriminant analysis. All the qualitative traits and body measurements showed highly significant breed difference except the tail base thickness. Values for most of the body measurements were higher in Begait cattle compared to the other cattle populations. The stepwise discriminant analysis extracted eighteen variables for characterizing the female populations and thirteen variables for the male populations. The pair-wise Mahalanobis distance showed the highest morphological distance between Begait and Irob, and the closest distance between Abergelle and Irob cattle populations. High correct assignment to source population was obtained for both sexes of all breeds except Abergelle and Irob. The discriminant function graph discerned each population with no clear distinction between Abergelle and Irob. These results indicate that the five cattle populations under investigation are clustered into four distinct breeds. However, the present phenotypic characterization should be confirmed with molecular genetic diversity investigation to use as a base in their conservation, breeding, and selection strategies.

First detection and molecular characterization of sapoviruses and noroviruses with zoonotic potential in swine in Ethiopia.

Noroviruses (NoVs) and sapoviruses (SaVs), which belong to the family Caliciviridae, are important human and animal enteric pathogens with zoonotic potential. In Ethiopia, no study has been done on the epidemiology of animal NoVs and SaVs. The aim of this study was to detect and characterize NoVs and SaVs from swine of various ages. Swine fecal samples (n = 117) were collected from commercial farms in Ethiopia. The samples were screened for caliciviruses by reverse transcription polymerase chain reaction (RT-PCR) using universal and genogroup-specific primer pairs. Phylogenetic analysis was conducted using a portion of the RNA-dependent RNA polymerase (RdRp) region and the VP1 region of genome sequences of caliciviruses. Among 117 samples, potential caliciviruses were detected by RT-PCR in 17 samples (14.5 %). Of the RT-PCR-positive fecal samples, four were sequenced, of which two were identified as human NoV GII.1 and the other two as porcine SaV GIII. The porcine SaV strains that were detected were genetically related to the porcine enteric calicivirus Cowden strain genogroup III (GIII), which is the prototype porcine SaV strain. No porcine NoVs were detected. Our results showed the presence of NoVs in swine that are most similar to human strains. These findings have important implications for NoV epidemiology and food safety. Therefore, continued surveillance of NoVs in swine is needed to define their zoonotic potential, epidemiology and public and animal health impact. This is the first study to investigate enteric caliciviruses (noroviruses and sapoviruses) in swine in Ethiopia.

Prevalence and molecular characterization of human noroviruses and sapoviruses in Ethiopia.

Viral gastroenteritis is a major public health problem worldwide. In Ethiopia, very limited studies have been done on the epidemiology of enteropathogenic viruses. The aim of this study was to detect and characterize noroviruses (NoVs) and sapoviruses (SaVs) from acute gastroenteritis patients of all ages. Fecal samples were collected from diarrheic patients (n = 213) in five different health centers in Addis Ababa during June-September 2013. The samples were screened for caliciviruses by reverse transcription polymerase chain reaction (RT-PCR) using universal and genogroup-specific primer pairs. Phylogenetic analyses were conducted using the sequences of the PCR products. Of the clinical samples, 25.3 % and 4.2 % were positive for NoV and SaV RNA, respectively. Among the norovirus positives, 22 were sequenced further, and diverse norovirus strains were identified: GI (n = 4), GII (n = 17) and GIV (n = 1). Most strains were GII (n = 17/22: 77.2 %), which were further divided into three different genotypes (GII.4, GII.12/GII.g recombinant-like and GII.17), with GII.17 being the dominant (7/17) strain detected. GI noroviruses, in particular GI.4 (n = 1), GI.5 (n = 2) and GI.8 (n = 1), were also detected and characterized. The GIV strain detected is the first from East Africa. The sapoviruses sequenced were also the first reported from Ethiopia. Collectively, this study showed the high burden and diversity of noroviruses and circulation of sapoviruses in diarrheic patients in Ethiopia. Continued surveillance to assess their association with diarrhea is needed to define their epidemiology, disease burden, and impact on public health.

Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa.

Bitter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. To better understand the genetic architecture and patterns of phenotypic variability of bitter taste perception, we sequenced a 996 bp region, encompassing the coding exon of TAS2R16, a bitter taste receptor gene, in 595 individuals from 74 African populations and in 94 non-Africans from 11 populations. We also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from Central and East Africa. In addition, we characterized TAS2R16 mutants in vitro to investigate the effects of polymorphic loci identified at this locus on receptor function. Here, we report striking signatures of positive selection, including significant Fay and Wu's H statistics predominantly in East Africa, indicating strong local adaptation and greater genetic structure among African populations than expected under neutrality. Furthermore, we observed a "star-like" phylogeny for haplotypes with the derived allele at polymorphic site 516 associated with increased bitter taste perception that is consistent with a model of selection for "high-sensitivity" variation. In contrast, haplotypes carrying the "low-sensitivity" ancestral allele at site 516 showed evidence of strong purifying selection. We also demonstrated, for the first time, the functional effect of nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse Africans and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression in vitro, suggesting that one main polymorphism at TAS2R16 influences salicin recognition. Additionally, we detected geographic differences in levels of bitter taste perception in Africa not previously reported and infer an East African origin for high salicin sensitivity in human populations.

Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa.

Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans.

Whole-genome resource sequences of 57 indigenous Ethiopian goats.

Domestic goats are distributed worldwide, with approximately 35% of the one billion world goat population occurring in Africa. Ethiopia has 52.5 million goats, ~99.9% of which are considered indigenous landraces deriving from animals introduced to the Horn of Africa in the distant past by nomadic herders. They have continued to be managed by smallholder farmers and semi-mobile pastoralists throughout the region. We report here 57 goat genomes from 12 Ethiopian goat populations sampled from different agro-climates. The data were generated through sequencing DNA samples on the Illumina NovaSeq 6000 platform at a mean depth of 9.71x and 150 bp pair-end reads. In total, ~2 terabytes of raw data were generated, and 99.8% of the clean reads mapped successfully against the goat reference genome assembly at a coverage of 99.6%. About 24.76 million SNPs were generated. These SNPs can be used to study the population structure and genome dynamics of goats at the country, regional, and global levels to shed light on the species' evolutionary trajectory.

Anthropogenic events and responses to environmental stress are shaping the genomes of Ethiopian indigenous goats.

Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We analyzed 57 Ethiopian indigenous domestic goat genomes alongside 67 equivalents of east, west, and north-west African, European, South Asian, Middle East, and wild Bezoar goats. Cluster, ADMIXTURE (K = 4) and phylogenetic analysis revealed four genetic groups comprising African, European, South Asian, and wild Bezoar goats. The Middle Eastern goats had an admixed genome of these four genetic groups. At K = 5, the West African Dwarf and Moroccan goats were separated from East African goats demonstrating a likely historical legacy of goat arrival and dispersal into Africa via the coastal Mediterranean Sea and the Horn of Africa. FST, XP-EHH, and Hp analysis revealed signatures of selection in Ethiopian goats overlaying genes for thermo-sensitivity, oxidative stress response, high-altitude hypoxic adaptation, reproductive fitness, pathogen defence, immunity, pigmentation, DNA repair, modulation of renal function and integrated fluid and electrolyte homeostasis. Notable examples include TRPV1 (a nociception gene); PTPMT1 (a critical hypoxia survival gene); RETREG (a regulator of reticulophagy during starvation), and WNK4 (a molecular switch for osmoregulation). These results suggest that human-mediated translocations and adaptation to contrasting environments are shaping indigenous African goat genomes.

Integrative functional genomic analyses identify genetic variants influencing skin pigmentation in Africans.

Skin color is highly variable in Africans, yet little is known about the underlying molecular mechanism. Here we applied massively parallel reporter assays to screen 1,157 candidate variants influencing skin pigmentation in Africans and identified 165 single-nucleotide polymorphisms showing differential regulatory activities between alleles. We combine Hi-C, genome editing and melanin assays to identify regulatory elements for MFSD12, HMG20B, OCA2, MITF, LEF1, TRPS1, BLOC1S6 and CYB561A3 that impact melanin levels in vitro and modulate human skin color. We found that independent mutations in an OCA2 enhancer contribute to the evolution of human skin color diversity and detect signals of local adaptation at enhancers of MITF, LEF1 and TRPS1, which may contribute to the light skin color of Khoesan-speaking populations from Southern Africa. Additionally, we identified CYB561A3 as a novel pigmentation regulator that impacts genes involved in oxidative phosphorylation and melanogenesis. These results provide insights into the mechanisms underlying human skin color diversity and adaptive evolution.

A review on characterization of BCR - ABL transcript variants for molecular monitoring of chronic myeloid leukemia phenotypes.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative growth of human pluripotent stem cells which is estimated to occur at a rate of 1/100000 populations every year worldwide. A characteristic feature of this disease is the presence of the Philadelphia chromosome genotype, which results from the reciprocal translocation between human chromosomes 9 and 22. Two types of major genotypes are involved, which consequently result in two major types of expressed fusion mRNA transcripts: b3a2 and b2a2, i.e. major breakpoint segments (happening after exon 13 & after exon 14) of the BCR gene on chromosome 22 fuze with the ABL1 gene breakpoint (happening after exon 2) on chromosome 9, forming two genotypes coding for two transcripts: b3a2 (e14a2) and b2a2 (e13a2). The protein 'p210 BCR-ABL1', a protein which characteristically exhibits a high tyrosine kinase activity which is followed by the activation of various cellular processes that lead to increased cellular proliferation and cancer, is coded by both major BCR - ABL1 mRNA transcripts. Recent developments in the treatment of CML through molecular monitoring of the disease have managed to reduce patient morbidity and mortality. Advanced molecular techniques are aimed at detecting BCR-ABL1 transcript levels to monitor treatment response. Transcript typing is necessary to detect minimal residual disease and to achieve molecular response by helping to provide selective therapy based on the type of transcript identified, as transcript type is correlated with the disease course.The purpose of this review is to discuss: the role of the BCR-ABL1 fusion gene in the pathogenesis of CML; the role of BCR-ABL1 transcript characterization in the molecular monitoring of CML therapy; the association of BCR - ABL1 transcript types with different CML phenotypes, molecular responses, and treatment responses; and the laboratory techniques employed to detect and characterize BCR - ABL1 transcripts.

Genome-wide diversity and admixture of five indigenous cattle populations from the Tigray region of northern Ethiopia.

The Tigray region, where we found around eight per cent of the indigenous cattle population of Ethiopia, is considered as the historic centre of the country, with the ancient pre-Aksumite and Aksumite civilisations in contact with the civilisations of the Fertile Crescent and the Indian subcontinent. Here, we used whole genome sequencing data to characterise the genomic diversity, relatedness, and admixture of five cattle populations (Abergelle, Arado, Begait, Erob, and Raya) indigenous to the Tigray region of Ethiopia. We detected 28 to 29 million SNPs and 2.7 to 2.9 million indels in each population, of which 7% of SNPs and 34% of indels were novel. Functional annotation of the variants showed around 0.01% SNPs and 0.22%-0.27% indels in coding regions. Enrichment analysis of genes overlapping missense private SNPs revealed 20 significant GO terms and KEGG pathways that were shared by or specific to breeds. They included important genes associated with morphology (SCN4A, TAS1R2 and KCNG4), milk yield (GABRG1), meat quality (MMRN2, VWC2), feed efficiency (PCDH8 and SLC26A3), immune response (LAMC1, PCDH18, CELSR1, TLR6 and ITGA5), heat resistance (NPFFR1 and HTR7) and genes belonging to the olfactory gene family, which may be related to adaptation to harsh environments. Tigray indigenous cattle are very diverse. Their genome-wide average nucleotide diversity ranged from 0.0035 to 0.0036. The number of heterozygous SNPs was about 0.6-0.7 times higher than homozygous ones. The within-breed average number of ROHs ranged from 777.82 to 1000.45, with the average sum of the length of ROHs ranging from 122.01 Mbp to 163.88 Mbp. The genomic inbreeding coefficients differed among animals and breeds, reaching up to 10% in some Begait and Raya animals. Tigray indigenous cattle shared a common ancestry with Asian indicine (85.6%-88.7%) and African taurine (11.3%-14.1%) cattle, with very small, if any, European taurine introgression. This study identified high within-breed genetic diversity representing an opportunity for breeding improvement programs and, also, significant novel variants that could increase the number of known cattle variants, an important contribution to the knowledge of domestic cattle genetic diversity.

Profile and Frequency of Mutations Conferring Drug-Resistant Tuberculosis in the Central, Southeastern and Eastern Ethiopia.

Purpose: Advances in molecular tools that assess genes harboring drug resistance mutations have greatly improved the detection and treatment of drug-resistant tuberculosis (DR-TB). This study was conducted to determine the frequency and type of mutations that are responsible for resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs) and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis (MTB) isolates obtained from culture-positive pulmonary tuberculosis (TB) patients in the central, southeastern and eastern Ethiopia. Patients and Methods: In total, 224 stored culture-positive MTB isolates from pulmonary TB patients referred to Adama and Harar regional TB laboratories between August 2018 and January 2019 were assessed for mutations conferring RIF, INH, FLQs and SLIDs resistance using GenoType®MTBDRplus (MTBDRplus) and GenoType®MTBDRsl (MTBDRsl). Results: RIF, INH, FLQs and SLIDs resistance-conferring mutations were identified in 88/224 (39.3%), 85/224 (38.0%), 7/77 (9.1%), and 3/77% (3.9%) of MTB isolates, respectively. Mutation codons rpoB S531L (59.1%) for RIF, katG S315T (96.5%) for INH, gyrA A90V (42.1%) for FLQs and WT1 rrs (100%) for SLIDs were observed in the majority of the isolates tested. Over a 10th of rpoB mutations detected in the current study were unknown. Conclusion: In this study, the most common mutations conferring drug resistance to RIF, INH, FLQs were identified. However, a significant proportion of RIF-resistant isolates manifested unknown rpoB mutations. Similarly, although few in number, all SLID-resistant isolates had unknown rrs mutations. To further elucidate the entire spectrum of mutations, tool such as whole-genome sequencing is imperative. Furthermore, the expansion of molecular drug susceptibility testing services is critical for tailoring patient treatment and preventing disease transmission.