Ethnic and Functional Differentiation of Copy Number Polymorphisms in Tunisian and HapMap Population Unveils Insights on Genome Organizational Plasticity

Overview

Journal Sci Rep

Specialty Science

Date 2024 Feb 27

PMID 38409353

Authors

Lilia Romdhane

Sameh Kefi

Nessrine Mezzi

Najla Abassi

Haifa Jmel

Safa Romdhane

Jingxuan Shan

Lotfi Chouchane

Sonia Abdelhak

Affiliations

Soon will be listed here.

Abstract

Admixture mapping has been useful in identifying genetic variations linked to phenotypes, adaptation and diseases. Copy number variations (CNVs) represents genomic structural variants spanning large regions of chromosomes reaching several megabases. In this investigation, the "Canary" algorithm was applied to 102 Tunisian samples and 991 individuals from eleven HapMap III populations to genotype 1279 copy number polymorphisms (CNPs). In this present work, we investigate the Tunisian population structure using the CNP makers previously identified among Tunisian. The study revealed that Sub-Saharan African populations exhibited the highest diversity with the highest proportions of allelic CNPs. Among all the African populations, Tunisia showed the least diversity. Individual ancestry proportions computed using STRUCTURE analysis revealed a major European component among Tunisians with lesser contribution from Sub-Saharan Africa and Asia. Population structure analysis indicated the genetic proximity with Europeans and noticeable distance from the Sub-Saharan African and East Asian clusters. Seven genes harbouring Tunisian high-frequent CNPs were identified known to be associated with 9 Mendelian diseases and/or phenotypes. Functional annotation of genes under selection highlighted a noteworthy enrichment of biological processes to receptor pathway and activity as well as glutathione metabolism. Additionally, pathways of potential concern for health such as drug metabolism, infectious diseases and cancers exhibited significant enrichment. The distinctive genetic makeup of the Tunisians might have been influenced by various factors including natural selection and genetic drift, resulting in the development of distinct genetic variations playing roles in specific biological processes. Our research provides a justification for focusing on the exclusive genome organization of this population and uncovers previously overlooked elements of the genome.

Citing Articles

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References

McCarroll S, Kuruvilla F, Korn J, Cawley S, Nemesh J, Wysoker A . Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat Genet. 2008; 40(10):1166-74. DOI: 10.1038/ng.238. View

Evanno G, Regnaut S, Goudet J . Detecting the number of clusters of individuals using the software STRUCTURE: a simulation study. Mol Ecol. 2005; 14(8):2611-20. DOI: 10.1111/j.1365-294X.2005.02553.x. View

Itsara A, Cooper G, Baker C, Girirajan S, Li J, Absher D . Population analysis of large copy number variants and hotspots of human genetic disease. Am J Hum Genet. 2009; 84(2):148-61. PMC: 2668011. DOI: 10.1016/j.ajhg.2008.12.014. View

Henidi B, Kaabachi S, Mbarik M, Zhioua A, Hamzaoui K . Glutathione S-transferase M1 and T1 gene polymorphisms and risk of endometriosis in Tunisian population. Hum Fertil (Camb). 2014; 18(2):128-33. DOI: 10.3109/14647273.2014.989925. View

Iafrate A, Feuk L, Rivera M, Listewnik M, Donahoe P, Qi Y . Detection of large-scale variation in the human genome. Nat Genet. 2004; 36(9):949-51. DOI: 10.1038/ng1416. View

Teo S, Ku C, Naidoo N, Hall P, Chia K, Salim A . A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals. J Hum Genet. 2011; 56(7):524-33. DOI: 10.1038/jhg.2011.52. View

He Y, Hoskins J, McLeod H . Copy number variants in pharmacogenetic genes. Trends Mol Med. 2011; 17(5):244-51. PMC: 3092840. DOI: 10.1016/j.molmed.2011.01.007. View

Ku C, Pawitan Y, Sim X, Ong R, Seielstad M, Lee E . Genomic copy number variations in three Southeast Asian populations. Hum Mutat. 2010; 31(7):851-7. DOI: 10.1002/humu.21287. View

Chbili C, Fathallah N, Laadhari C, Ouni B, Saguem S, Ben Fredj M . Glutathione-S-transferase genetic polymorphism and risk of hepatotoxicity to antitubercular drugs in a North-African population: A case-control study. Gene. 2021; 809:146019. DOI: 10.1016/j.gene.2021.146019. View

10.

Yim S, Kim T, Hu H, Kim J, Kim B, Lee J . Copy number variations in East-Asian population and their evolutionary and functional implications. Hum Mol Genet. 2009; 19(6):1001-8. PMC: 2830825. DOI: 10.1093/hmg/ddp564. View

11.

Johansson I, Ingelman-Sundberg M . CNVs of human genes and their implication in pharmacogenetics. Cytogenet Genome Res. 2009; 123(1-4):195-204. DOI: 10.1159/000184709. View

12.

Conrad D, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y . Origins and functional impact of copy number variation in the human genome. Nature. 2009; 464(7289):704-12. PMC: 3330748. DOI: 10.1038/nature08516. View

13.

Veerappa A, Vishweswaraiah S, Lingaiah K, Murthy M, V Suresh R, Manjegowda D . Global spectrum of copy number variations reveals genome organizational plasticity and proposes new migration routes. PLoS One. 2015; 10(4):e0121846. PMC: 4409114. DOI: 10.1371/journal.pone.0121846. View

14.

Meijerman I, Sanderson L, Smits P, Beijnen J, Schellens J . Pharmacogenetic screening of the gene deletion and duplications of CYP2D6. Drug Metab Rev. 2007; 39(1):45-60. DOI: 10.1080/03602530600952206. View

15.

Sudmant P, Rausch T, Gardner E, Handsaker R, Abyzov A, Huddleston J . An integrated map of structural variation in 2,504 human genomes. Nature. 2015; 526(7571):75-81. PMC: 4617611. DOI: 10.1038/nature15394. View

16.

Riou S, El Younsi C, Chaabouni H . [Consanguinity in the population of northern Tunisia]. Tunis Med. 1989; 67(3):167-72. View

17.

Ueno N, Wilson M . Receptor-mediated phagocytosis of Leishmania: implications for intracellular survival. Trends Parasitol. 2012; 28(8):335-44. PMC: 3399048. DOI: 10.1016/j.pt.2012.05.002. View

18.

Park H, Kim J, Ju Y, Gokcumen O, Mills R, Kim S . Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing. Nat Genet. 2010; 42(5):400-5. PMC: 3329635. DOI: 10.1038/ng.555. View

19.

Nyangiri O, Noyes H, Mulindwa J, Ilboudo H, Kabore J, Ahouty B . Copy number variation in human genomes from three major ethno-linguistic groups in Africa. BMC Genomics. 2020; 21(1):289. PMC: 7147055. DOI: 10.1186/s12864-020-6669-y. View

20.

Garte S, Gaspari L, Alexandrie A, Ambrosone C, Autrup H, Autrup J . Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev. 2001; 10(12):1239-48. View