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      Copy number variation of CCL3L1 among three major ethnic groups in Malaysia

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          Abstract

          Background

          C-C motif Chemokine Ligand 3 Like 1 ( CCL3L1) is a multiallelic copy number variable, which plays a crucial role in immunoregulatory and hosts defense through the production of macrophage inflammatory protein (MIP)-1α. Variable range of the CCL3L1 copies from 0 to 14 copies have been documented in several different populations. However, there is still lack of report on the range of CCL3L1 copy number exclusively among Malaysians who are a multi-ethnic population. Thus, this study aims to extensively examine the distribution of CCL3L1 copy number in the three major populations from Malaysia namely Malay, Chinese and Indian. A diploid copy number of CCL3L1 for 393 Malaysians (Malay = 178, Indian = 90, and Chinese = 125) was quantified using Paralogue Ratio Tests (PRTs) and then validated with microsatellites analysis.

          Results

          To our knowledge, this is the first report on the CCL3L1 copy number that has been attempted among Malaysians and the Chinese ethnic group exhibits a diverse pattern of CCL3L1 distribution copy number from the Malay and Indian ( p < 0.0001). The CCL3L1 ranged from 0 to 8 copies for both the Malay and Indian ethnic groups while 0 to 10 copies for the Chinese ethnic. Consequently, the CCL3L1 copy number among major ethnic groups in the Malaysian population is found to be significantly varied when compared to the European population ( p < 0.0001). The mean/median reported for the Malay, Chinese, Indian, and European are 2.759/2.869, 3.453/3.290, 2.437/1.970 and 2.001/1.940 respectively.

          Conclusion

          This study reveals the existence of genetic variation of CCL3L1 in the Malaysian population, and suggests by examining genetic diversity on the ethnicity, and specific geographical region could help in reconstructing human evolutionary history and for the prediction of disease risk related to the CCL3L1 copy number.

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          Most cited references48

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          The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility.

          Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.
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            Mapping human genetic diversity in Asia.

            Asia harbors substantial cultural and linguistic diversity, but the geographic structure of genetic variation across the continent remains enigmatic. Here we report a large-scale survey of autosomal variation from a broad geographic sample of Asian human populations. Our results show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography. Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene flow among populations. More than 90% of East Asian (EA) haplotypes could be found in either Southeast Asian (SEA) or Central-South Asian (CSA) populations and show clinal structure with haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic source of EA populations.
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              Deep whole-genome sequencing of 100 southeast Asian Malays.

              Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                jaylajamal@yahoo.com
                nurkhairinakhair@gmail.com
                shamenivinod@gmail.com
                zulkefley_os@upm.edu.my
                suhaili_ab@upm.edu.my
                Journal
                BMC Genet
                BMC Genet
                BMC Genetics
                BioMed Central (London )
                1471-2156
                3 January 2020
                3 January 2020
                2020
                : 21
                : 1
                Affiliations
                ISNI 0000 0001 2231 800X, GRID grid.11142.37, Department of Biomedical Science, Faculty of Medicine and Health Sciences, , Universiti Putra Malaysia, ; UPM, 43400 Serdang, Selangor Malaysia
                Author information
                http://orcid.org/0000-0002-2217-4509
                Article
                803
                10.1186/s12863-019-0803-3
                6942282
                31900126
                54bed1f7-b8b4-46fe-94bc-b033f6eb3b06
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 May 2018
                : 17 December 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003093, Ministry of Higher Education, Malaysia;
                Award ID: FRGS-2013 (2) 5524413
                Award Recipient :
                Funded by: Ministry of Higher Education Malaysia
                Award ID: MyBrain15
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Genetics
                copy number variation,cnv,ccl3l1,malaysian population,paralogue ratio test,prt
                Genetics
                copy number variation, cnv, ccl3l1, malaysian population, paralogue ratio test, prt

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