16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Extreme founder effect associated with hyperglycemia and hyperlipidemia on the island of NIAS/Indonesia

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The island of Nias/Indonesia shows an extremely reduced genetic diversity indicating a strong founder effect. As a consequence, the prevalence of some disease genes should significantly differ among populations depending on the gene pool passed on to the founder population and their successive expansion as it has already been documented for several monogenic diseases. Results of the current study based on routine laboratory blood examination give rise to the notion that this might also hold true for polygenic disorders. We observed very high prevalence of hyperglycemia (non-fasting glucose above 200 mg/dL in 14 % Nias population compared to 1.5 % in the population of the neighboring island of Sumatra) accompanied by hypertriglyceridemia, high non-HDL-cholesterol, and low HDL-cholesterol levels. These findings suggest that the Nias population may be disproportionally affected by prediabetes and type 2 diabetes mellitus. By contrast, laboratory parameters potentially indicative of other polygenic disorders such as total plasma cholesterol, electrolytes, creatinine, urea, and uric acid were comparable between the inhabitants of Nias and Sumatra islands. To our knowledge this is the first study suggesting that the extremely strong genetic bottleneck seen in the Nias population translates into the widespread metabolic disease with potentially deleterious influence on public health.

          Highlights

          • The native population of the Island of Nias is disproportionately affected from hyperglycemia and hypertriglyceridemia.

          • This may result from a genetic bottleneck effect previously documented for rare monogenic but not common metabolic disorders.

          • The increased prevalence of diabetes mellitus type 2/prediabetes may seriously affect public health on Nias.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: found
          • Article: not found

          Skeletal dysplasia in a consanguineous clan from the island of Nias/Indonesia is caused by a novel mutation in B3GAT3.

          We describe a large family with disproportionate short stature and bone dysplasia from Nias in which we observed differences in severity when comparing the phenotypes of affected individuals from two remote branches. We conducted a linkage scan in the more severely affected family branch and determined a critical interval of 4.7 cM on chromosome 11. Sequencing of the primary candidate gene TBX10 did not reveal a disease-causing variant. When performing whole exome sequencing we noticed a homozygous missense variant in B3GAT3, c.419C>T [p.(Pro140Leu)]. B3GAT3 encodes β-1,3-glucuronyltransferase-I (GlcAT-I). GlcAT-I catalyzes an initial step of proteoglycan synthesis and the mutation p. (Pro140Leu) lies within the donor substrate-binding subdomain of the catalytic domain. In contrast to the previously published mutation in B3GAT3, c.830G>A [p.(Arg277Gln)], no heart phenotype could be detected in our family. Functional studies revealed a markedly reduced GlcAT-I activity in lymphoblastoid cells from patients when compared to matched controls. Moreover, relative numbers of glycosaminoglycan (GAG) side chains were decreased in patient cells. We found that Pro140Leu-mutant GlcAT-I cannot efficiently transfer GlcA to the linker region trisaccharide. This failure results in a partial deficiency of both chondroitin sulfate and heparan sulfate chains. Since the phenotype of the Nias patients differs from the Larsen-like syndrome described for patients with mutation p.(Arg277Gln), we suggest mutation B3GAT3:p.(Pro140Leu) to cause a different type of GAG linkeropathy showing no involvement of the heart.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The Finnish disease heritage database (FinDis) update-a database for the genes mutated in the Finnish disease heritage brought to the next-generation sequencing era.

            The Finnish Disease Heritage Database (FinDis) (http://findis.org) was originally published in 2004 as a centralized information resource for rare monogenic diseases enriched in the Finnish population. The FinDis database originally contained 405 causative variants for 30 diseases. At the time, the FinDis database was a comprehensive collection of data, but since 1994, a large amount of new information has emerged, making the necessity to update the database evident. We collected information and updated the database to contain genes and causative variants for 35 diseases, including six more genes and more than 1,400 additional disease-causing variants. Information for causative variants for each gene is collected under the LOVD 3.0 platform, enabling easy updating. The FinDis portal provides a centralized resource and user interface to link information on each disease and gene with variant data in the LOVD 3.0 platform. The software written to achieve this has been open-sourced and made available on GitHub (http://github.com/findis-db), allowing biomedical institutions in other countries to present their national data in a similar way, and to both contribute to, and benefit from, standardized variation data. The updated FinDis portal provides a unique resource to assist patient diagnosis, research, and the development of new cures. © 2013 WILEY PERIODICALS, INC.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Unexpected island effects at an extreme: reduced Y chromosome and mitochondrial DNA diversity in Nias.

              The amount of genetic diversity in a population is determined by demographic and selection events in its history. Human populations which exhibit greatly reduced overall genetic diversity, presumably resulting from severe bottlenecks or founder events, are particularly interesting, not least because of their potential to serve as valuable resources for health studies. Here, we present an unexpected case, the human population of Nias Island in Indonesia, that exhibits severely reduced Y chromosome (non-recombining portion of the Y chromosome [NRY]) and to a lesser extent also reduced mitochondrial DNA (mtDNA) diversity as compared with most other populations from the Asia/Oceania region. Our genetic data, collected from more than 400 individuals from across the island, suggest a strong previously undetected bottleneck or founder event in the human population history of Nias, more pronounced for males than for females, followed by subsequent genetic isolation. Our findings are unexpected given the island's geographic proximity to the genetically highly diverse Southeast Asian world, as well as our previous knowledge about the human history of Nias. Furthermore, all NRY and virtually all mtDNA haplogroups observed in Nias can be attributed to the Austronesian expansion, in line with linguistic data, and in contrast with archaeological evidence for a pre-Austronesian occupation of Nias that, as we show here, left no significant genetic footprints in the contemporary population. Our work underlines the importance of human genetic diversity studies not only for a better understanding of human population history but also because of the potential relevance for genetic disease-mapping studies.
                Bookmark

                Author and article information

                Contributors
                Journal
                Atheroscler Plus
                Atheroscler Plus
                Atherosclerosis Plus
                Elsevier
                2667-0909
                2667-0895
                23 July 2024
                September 2024
                23 July 2024
                : 57
                : 26-29
                Affiliations
                [a ]Institute of Human Genetics, University of Münster, Münster, Germany
                [b ]Yayasan Pusaka Nias (YPN), Gunungsitoli, Sumatera Utara, Indonesia
                [c ]Central Laboratory Facility, University Hospital Münster, Münster, Germany
                [d ]Institute for Laboratory Medicine, Microbiology and Transfusion Medicine, Maria-Hospital Osnabrück, Niels-Stensen-Kliniken GmbH, Germany
                Author notes
                [* ]Corresponding author. Zentrale Einrichtung UKM-Labor, Universitätsklinikum Münster, Albert-Schweizer-Campus 1, Geb. A1, 48149, Münster, TL, Germany. nofer@ 123456uni-muenster.de
                [** ]Corresponding author.
                Article
                S2667-0895(24)00017-8
                10.1016/j.athplu.2024.07.002
                11331701
                39161624
                b140b4ed-3404-466f-9c9c-40900e672f66
                © 2024 The Authors

                This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

                History
                : 5 May 2024
                : 2 July 2024
                : 15 July 2024
                Categories
                Full Length Article

                island of nias,genetic bottleneck,hyperglycemia,hyperlipidemia

                Comments

                Comment on this article