An integrated personal and population-based Egyptian genome reference

Wohlers, Inken; Künstner, Axel; Munz, Matthias; Olbrich, Michael; Fähnrich, Anke; Calonga‐Solís, Verónica; Ma, Cun‐Gen; Hirose, Misa; El-Mosallamy, Shaaban; Salama, Mohamed; Busch, Hauke; Ibrahim, Saleh M.

doi:10.1038/s41467-020-17964-1

Cited by 29 publications

(39 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We find that North and East African mitochondrial genomes are phylogenetically diverse and cover nearly all major clades worldwide. Likewise, specific subclades are prevalent in the region, supporting that North and East Africa, and particularly Northeast Africa harbors ancestry components typically attributed to Africa, Europe and Asia (19) , all of which are likely present in the region since prehistoric times (41). Further, several North or East African clade representatives highlighted by our work and not studied in-depth so far may still add further information to worldwide maternal human genetic history, e.g., the haplogroups L4, L6, N, I and X.…”

Section: Discussionmentioning

confidence: 85%

North and East African mitochondrial genetic variation needs further characterization towards precision medicine

Fähnrich

Stephan

Hirose

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Mitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as disease susceptibility of human populations across the globe. This requires a comprehensive catalogue of commonly observed genetic variations in the mitochondria for all regions throughout the world. So far, however, certain regions, such as North and East Africa have been understudied. Towards this, we have created the most comprehensive quality-controlled North and East African mitochondrial dataset to date by compiling 11 published cohorts with novel data of mitochondrial genomes from 159 Sudanese individuals. We combined these 641 mitochondrial sequences with sequences from the 1000 Genomes (n=2,504) and the Human Genome Diversity Project (n=828) and used the tool haplocheck for extensive quality control and detection of in-sample contamination. Using a subset of high-coverage mitochondrial sequences we predict 15 potentially novel haplogroups in North and East African subjects and observe likely phylogenetic deviations from the established PhyloTree reference for haplogroups L0a1 and L2a1. This demonstrates common hitherto unexplored variants in mitochondrial genomes of the North and East African region that lead to novel phylogenetic relationships, calling for further in-depth population genetic studies in that region.

show abstract

Section: Discussionmentioning

confidence: 85%

North and East African mitochondrial genetic variation needs further characterization towards precision medicine

Fähnrich

Stephan

Hirose

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have extended our study to sequence the first Zoroastrian-Parsi male genome, presently 2,589,561,354 bp in length with 87.46% genome fraction mapping to GRCh38 (Appendix 9). The genome completeness is 93.25% which is on par compared to other high resolution whole genomes from the Ashkenazi 16 , Egypt ref 48 and Yoruba genome 49 assembly projects. Our assembly quality is further enhanced by BUSCO completeness score of 88.3% validating our benchmarking process for genome completeness.…”

Section: Discussionmentioning

confidence: 89%

Ancient Migrations - The first complete genome assembly, annotation and variants of the Zoroastrian-Parsi community of India

Pasha

Krishnasamy

Naveenkumar

et al. 2021

Preprint

View full text Add to dashboard Cite

With the advent of Next Generation Sequencing, many population specific whole genome sequences published thus far, predominantly represent individuals of European ancestry. While sequencing efforts of underrepresented communities in genomes datasets, like the Yoruba West-African, Han Chinese, Tibetan, South Korean, Egyptian and Japanese have recently added to the public genomic repositories, a comprehensive understanding of human genomic diversity and discovery of trait-associated variants necessitates the need for additional population specific analysis. In this context, the genomics of the population from the Indian sub-continent, given its genetic heterogeneity needs further elucidation. In this context, the endogamous Zoroastrian-Parsi community of India, offer an exceptional insight into a homogenous population that has culturally, socially, and genetically remained intact, for 13 centuries amidst the genomic, social and cultural Indian landscape, consequent to their migration from the ancient Persian plateau. Notwithstanding longevity as a trait, this endangered community is highly susceptible to cancers, rare genetic disorders, and display a documented high incidence of neurodegenerative and autoimmune conditions. The community as a matter of cultural practice abstains from smoking. Here, we describe the assembly and annotation of the genome of an adult female, Zoroastrian-Parsi individual sequenced at a high depth of 173X using a combination of short Illumina reads (160X) and long nanopore reads (13X). Using a combination of hybrid assemblers, we created a new, population-specific human reference genome, The Zoroastrian-Parsi Genome Reference Female, AGENOME-ZPGRF, contains 2,778,216,114 nucleotides as compared to 3,096,649,726 in GRCh38 constituting 93.235% of the total genomic fraction. Annotation identified 20833 genomic features, of which 14996 are almost identical to their counterparts on GRCh38 while 5837 genomic features were covered in partial. AGENOME-ZPGRF contained 5,426,310 variants of which the majority were SNPs (4,291,601) and 960,867 SNPs were AGENOME-ZPGRF specific personal variants not listed in dbSNP. We present, AGENOME-ZPGRF as a whole reference for any genetic studies involving Zoroastrian-Parsi individuals extending their application to identify disease relevant prognostic biomarkers and variants in global population genomics studies.

show abstract

“…We found the rs6226 GG genotype variant to be significantly less frequent in the Egyptian population compared to the EAS population ( p = 0.022). We found only one missense FURIN variant covered in the Egyptian-genome study data [ 28 ]. rs148110342 was absent in the EAS population and reported with a low AF in the Egyptian population (AF = 0.014).…”

Section: Resultsmentioning

confidence: 99%

“…Our analysis also focused on common exonic variants of TMPRSS2 ; three SNPs showed significantly ( p < 0.0002) different frequencies when comparing the Egyptian population with the East Asian population (rs2298659, rs17854725 and rs12329760) ( p = 0.0002, p < 0.0001 and p < 0.0001 respectively) ( Table 1 ). After investigating their frequencies in the Egyptian-genome study data [ 28 ], we found that variant rs28401567 is significantly less frequent in the Egyptian population in comparison to the East-Asian population ( p ≤ 0.0001).…”

Section: Resultsmentioning

confidence: 99%

“…Both rs2070788 GG and GG genotypes of rs383510 variants were found to be relatively more frequent in the Egyptian-genome study data (28) (AF = 0.528 and 0.56, respectively). The rs464397 TT genotype was associated with higher expression of TMPRSS2 in lung tissues and the variant has been found to be more frequent in the Egyptian population (28), with an allele frequency of 0.593, in relation to African and East-Asian populations (p = 0.0028 and p < 0.0001, respectively).…”

Section: Frequencies Of Regulatory Intronic Variants Of Tmprss2mentioning

confidence: 95%

See 1 more Smart Citation

Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2

Tarek

Abdelzaher

Kobeissy

et al. 2021

Genes

View full text Add to dashboard Cite

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2’s receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN’s potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

show abstract

An integrated personal and population-based Egyptian genome reference

Cited by 29 publications

References 75 publications

North and East African mitochondrial genetic variation needs further characterization towards precision medicine

North and East African mitochondrial genetic variation needs further characterization towards precision medicine

Ancient Migrations - The first complete genome assembly, annotation and variants of the Zoroastrian-Parsi community of India

Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2

Contact Info

Product

Resources

About