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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<div about="/news-events/nih-research-matters/repeats-genetic-code-underlie-some-human-variation" typeof="sioc:Item foaf:Document" class="ds-1col node node--nih-research-matters view-mode-full node--full node--nih-research-matters--full clearfix">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2021-10-19T00:00:00-04:00" class="date-display-single">October 19, 2021</span></p><div class='syndicate'><h1>Repeats in the genetic code underlie some human variation</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>Researchers found that differences in repeats of DNA explain substantial variations in height, kidney function, hair curl, and blood lipids.</li>
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<li>Such repeats in the genetic code may also play a role in other human traits, including the risk for—and outcomes of—disease.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Diverse people of different heights and other traits">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2021/20211019-dna.jpg?itok=AVEHNLCg&timestamp=1634650654 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2021/20211019-dna.jpg?itok=E2Z3zVQD&timestamp=1634650654 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2021/20211019-dna.jpg?itok=D8sdnqBx&timestamp=1634650654 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2021/20211019-dna.jpg?itok=UOiI9I_i&timestamp=1634650654 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2021/20211019-dna.jpg?itok=4HjzbPMm&timestamp=1634650654 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2021/20211019-dna.jpg?itok=E2Z3zVQD&timestamp=1634650654" alt="Diverse people of different heights and other traits" title="Diverse people of different heights and other traits" />
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</picture><span class="caption">The study found that repeats in the genetic code may play a previously unrecognized role in many human traits. </span><span class="credit">Rawpixel.com / Shutterstock</span></div>
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</div><p>Variations in the human genome—the complete set of human DNA—drive individual differences in appearance, health, and more. In 2003, the Human Genome Project finished sequencing the first human genome. Since then, researchers have been combing through these genetic blueprints for clues to health and disease.</p>
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||
<p>Studies called genome-wide association studies, or GWAS, have looked at variations in DNA between different people. Most have focused on small, single base pair changes in the genetic code. While these studies have yielded important insights, much about how traits are inherited and differ between individuals still remains unexplained.</p>
|
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||
<p>Variable number of tandem repeat polymorphisms, or VNTRs, are a less studied but common type of genetic variation. These are DNA sequences that are repeated over and over again in a row. Such repeats can vary in number between people from just a few to hundreds in the same gene. When these occur within protein-coding genes, they generate proteins of different sizes. But VNTRs have been difficult to study.</p>
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<p>To look more closely at VNTRs, researchers from the Broad Institute at MIT and Harvard University developed new methods to measure these long DNA repeats. They then examined the associations between VNTRs and variations in specific traits. The scientists focused on 118 protein-coding VNTRs and examined their association with nearly 800 traits.</p>
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<p>The data used came from more than 400,000 participants in the UK Biobank study. The study was supported by several NIH components. Results were published on September 24, 2021, in <em>Science</em>.</p>
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<p>Traits associated with VNTRs included height, kidney function, hair curl, and blood levels of a lipid called lipoprotein(a), or Lp(a), which is linked to heart disease.</p>
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<p>The team found that more than 80% of the variation in Lp(a) found in different people could be explained by repeat length variation and other inherited differences in <em>LPA</em>, a gene that codes for a component of Lp(a). These differences also explained most of the variability in average Lp(a) levels between populations of African and European ancestry.</p>
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<p>VNTRs in two different genes were associated with inherited variations in height. Differences in the number of VNTRs in one of these genes accounted for more than an inch of height variation between people in the study. The proteins encoded by the two genes play roles in cartilage and bone—two tissues that are important for growth.</p>
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<p>The number of repeats in another gene appeared to affect the levels of several commonly measured markers of kidney function as well as susceptibility to gout. However, the variations did not seem to influence the risk of chronic kidney disease.</p>
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<p>VNTR length variation in another gene associated strongly with male-pattern baldness, as well as whether hair was curly or straight. The protein encoded by the gene is known to contribute to the strength of hair roots.</p>
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<p>“Our findings show that there can be really potent effects from these VNTRs,” says Bob Handsaker, one of the study’s lead authors. “It’s more evidence that these complex regions of the genome can be really important and need more study.”</p>
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<p>This analysis of 118 protein-coding VNTRs—done in people primarily of European ancestry—provides a roadmap for much further study. There are many thousands of estimated repeats in the genome. Further analyses of VNTRs in more diverse populations may open broad new opportunities for understanding the role of genetic repeats in human diversity and disease.</p>
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<p>—by Sharon Reynolds</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/largest-catalogue-human-genetic-diversity" target="_top">Largest Catalog of Human Genetic Diversity</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/charting-genetic-variation-across-globe" target="_top">Charting Genetic Variation Across the Globe</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/landscape-gene-expression-human-body" target="_top">Landscape of Gene Expression in the Human Body</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/comparing-mouse-human-genomes" target="_top">Comparing the Mouse and Human Genomes</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/expanding-our-understanding-genomics" target="_top">Expanding Our Understanding of Genomics</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/revealing-human-proteome" target="_top">Revealing the Human Proteome</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/finding-treasure-junk-dna" target="_top">Finding Treasure in “Junk” DNA</a></li><li><a href="https://medlineplus.gov/lab-tests/lipoprotein-a-blood-test/" target="_top">Lipoprotein (a) Blood Test</a></li><li><a href="https://www.genome.gov/human-genome-project" target="_top">The Human Genome Project</a></li><li><a href="https://www.genome.gov/health/Genomics-and-Medicine" target="_top">Genomics and Medicine</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/34554798/">Protein-coding repeat polymorphisms strongly shape diverse human phenotypes.</a> Mukamel RE, Handsaker RE, Sherman MA, Barton AR, Zheng Y, McCarroll SA, Loh PR. <em>Science</em>. 2021 Sep 24;373(6562):1499-1505. doi: 10.1126/science.abg8289. Epub 2021 Sep 23. PMID: 34554798.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Human Genome Research Institute (NHGRI), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Mental Health (NIMH), and National Institute of Environmental Health Sciences (NIEHS); National Science Foundation; MIT John W. Jarve (1978) Seed Fund for Science Innovation; Burroughs Wellcome Fund; Next Generation Fund at the Broad Institute of MIT and Harvard; Alfred P. Sloan Foundation; Wellcome Trust; Medical Research Council; European Union; Chronic Disease Research Foundation; Zoe Global Ltd.; National Institute for Health Research; King’s College London.</p>
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