Publications by authors named "Nathan Nakatsuka"

11 Publications

  • Page 1 of 1

Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans.

Sci Rep 2020 10 9;10(1):16902. Epub 2020 Oct 9.

Department of Genetics, Harvard Medical School, New Research Building, Boston, MA, 02115, USA.

Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-74035-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547691PMC
October 2020

ContamLD: estimation of ancient nuclear DNA contamination using breakdown of linkage disequilibrium.

Genome Biol 2020 08 10;21(1):199. Epub 2020 Aug 10.

Department of Genetics, New Research Building, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, MA, 02115, USA.

We report a method called ContamLD for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of contaminant DNA. ContamLD leverages the idea that contaminants should have haplotypes uncorrelated to those of the studied individual. Using simulated data, we confirm that ContamLD accurately infers contamination rates with low standard errors: for example, less than 1.5% standard error in cases with less than 10% contamination and 500,000 sequences covering SNPs. This method is optimized for application to aDNA, taking advantage of characteristic aDNA damage patterns to provide calibrated contamination estimates, and is available at https://github.com/nathan-nakatsuka/ContamLD .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-020-02111-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418405PMC
August 2020

Ancient genomes in South Patagonia reveal population movements associated with technological shifts and geography.

Nat Commun 2020 08 3;11(1):3868. Epub 2020 Aug 3.

Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.

Archaeological research documents major technological shifts among people who have lived in the southern tip of South America (South Patagonia) during the last thirteen millennia, including the development of marine-based economies and changes in tools and raw materials. It has been proposed that movements of people spreading culture and technology propelled some of these shifts, but these hypotheses have not been tested with ancient DNA. Here we report genome-wide data from 20 ancient individuals, and co-analyze it with previously reported data. We reveal that immigration does not explain the appearance of marine adaptations in South Patagonia. We describe partial genetic continuity since ~6600 BP and two later gene flows correlated with technological changes: one between 4700-2000 BP that affected primarily marine-based groups, and a later one impacting all <2000 BP groups. From ~2200-1200 BP, mixture among neighbors resulted in a cline correlated to geographic ordering along the coast.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17656-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400565PMC
August 2020

Integration of ancient DNA with transdisciplinary dataset finds strong support for Inca resettlement in the south Peruvian coast.

Proc Natl Acad Sci U S A 2020 08 13;117(31):18359-18368. Epub 2020 Jul 13.

University of California, Santa Cruz (UCSC) Paleogenomics, Department of Anthropology, University of California, Santa Cruz, CA 95064.

Ancient DNA (aDNA) analysis provides a powerful means of investigating human migration, social organization, and a plethora of other crucial questions about humanity's past. Recently, specialists have suggested that the ideal research design involving aDNA would include multiple independent lines of evidence. In this paper, we adopt a transdisciplinary approach integrating aDNA with archaeological, biogeochemical, and historical data to investigate six individuals found in two cemeteries that date to the Late Horizon (1400 to 1532 CE) and Colonial (1532 to 1825 CE) periods in the Chincha Valley of southern Peru. Genomic analyses indicate that these individuals are genetically most similar to ancient and present-day populations from the north Peruvian coast located several hundred kilometers away. These genomic data are consistent with 16th century written records as well as ceramic, textile, and isotopic data. These results provide some of the strongest evidence yet of state-sponsored resettlement in the pre-Colonial Andes. This study highlights the power of transdisciplinary research designs when using aDNA data and sets a methodological standard for investigating ancient mobility in complex societies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2005965117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414190PMC
August 2020

A Paleogenomic Reconstruction of the Deep Population History of the Andes.

Cell 2020 05 7;181(5):1131-1145.e21. Epub 2020 May 7.

UCSC Paleogenomics, University of California, Santa Cruz, Santa Cruz, CA 95064, USA; UCSC Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. Electronic address:

There are many unanswered questions about the population history of the Central and South Central Andes, particularly regarding the impact of large-scale societies, such as the Moche, Wari, Tiwanaku, and Inca. We assembled genome-wide data on 89 individuals dating from ∼9,000-500 years ago (BP), with a particular focus on the period of the rise and fall of state societies. Today's genetic structure began to develop by 5,800 BP, followed by bi-directional gene flow between the North and South Highlands, and between the Highlands and Coast. We detect minimal admixture among neighboring groups between ∼2,000-500 BP, although we do detect cosmopolitanism (people of diverse ancestries living side-by-side) in the heartlands of the Tiwanaku and Inca polities. We also highlight cases of long-range mobility connecting the Andes to Argentina and the Northwest Andes to the Amazon Basin. VIDEO ABSTRACT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2020.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304944PMC
May 2020

An Ancient Harappan Genome Lacks Ancestry from Steppe Pastoralists or Iranian Farmers.

Cell 2019 10 5;179(3):729-735.e10. Epub 2019 Sep 5.

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

We report an ancient genome from the Indus Valley Civilization (IVC). The individual we sequenced fits as a mixture of people related to ancient Iranians (the largest component) and Southeast Asian hunter-gatherers, a unique profile that matches ancient DNA from 11 genetic outliers from sites in Iran and Turkmenistan in cultural communication with the IVC. These individuals had little if any Steppe pastoralist-derived ancestry, showing that it was not ubiquitous in northwest South Asia during the IVC as it is today. The Iranian-related ancestry in the IVC derives from a lineage leading to early Iranian farmers, herders, and hunter-gatherers before their ancestors separated, contradicting the hypothesis that the shared ancestry between early Iranians and South Asians reflects a large-scale spread of western Iranian farmers east. Instead, sampled ancient genomes from the Iranian plateau and IVC descend from different groups of hunter-gatherers who began farming without being connected by substantial movement of people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2019.08.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800651PMC
October 2019

The formation of human populations in South and Central Asia.

Authors:
Vagheesh M Narasimhan Nick Patterson Priya Moorjani Nadin Rohland Rebecca Bernardos Swapan Mallick Iosif Lazaridis Nathan Nakatsuka Iñigo Olalde Mark Lipson Alexander M Kim Luca M Olivieri Alfredo Coppa Massimo Vidale James Mallory Vyacheslav Moiseyev Egor Kitov Janet Monge Nicole Adamski Neel Alex Nasreen Broomandkhoshbacht Francesca Candilio Kimberly Callan Olivia Cheronet Brendan J Culleton Matthew Ferry Daniel Fernandes Suzanne Freilich Beatriz Gamarra Daniel Gaudio Mateja Hajdinjak Éadaoin Harney Thomas K Harper Denise Keating Ann Marie Lawson Matthew Mah Kirsten Mandl Megan Michel Mario Novak Jonas Oppenheimer Niraj Rai Kendra Sirak Viviane Slon Kristin Stewardson Fatma Zalzala Zhao Zhang Gaziz Akhatov Anatoly N Bagashev Alessandra Bagnera Bauryzhan Baitanayev Julio Bendezu-Sarmiento Arman A Bissembaev Gian Luca Bonora Temirlan T Chargynov Tatiana Chikisheva Petr K Dashkovskiy Anatoly Derevianko Miroslav Dobeš Katerina Douka Nadezhda Dubova Meiram N Duisengali Dmitry Enshin Andrey Epimakhov Alexey V Fribus Dorian Fuller Alexander Goryachev Andrey Gromov Sergey P Grushin Bryan Hanks Margaret Judd Erlan Kazizov Aleksander Khokhlov Aleksander P Krygin Elena Kupriyanova Pavel Kuznetsov Donata Luiselli Farhod Maksudov Aslan M Mamedov Talgat B Mamirov Christopher Meiklejohn Deborah C Merrett Roberto Micheli Oleg Mochalov Samariddin Mustafokulov Ayushi Nayak Davide Pettener Richard Potts Dmitry Razhev Marina Rykun Stefania Sarno Tatyana M Savenkova Kulyan Sikhymbaeva Sergey M Slepchenko Oroz A Soltobaev Nadezhda Stepanova Svetlana Svyatko Kubatbek Tabaldiev Maria Teschler-Nicola Alexey A Tishkin Vitaly V Tkachev Sergey Vasilyev Petr Velemínský Dmitriy Voyakin Antonina Yermolayeva Muhammad Zahir Valery S Zubkov Alisa Zubova Vasant S Shinde Carles Lalueza-Fox Matthias Meyer David Anthony Nicole Boivin Kumarasamy Thangaraj Douglas J Kennett Michael Frachetti Ron Pinhasi David Reich

Science 2019 09;365(6457)

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization's decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aat7487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822619PMC
September 2019

Reconstructing the Deep Population History of Central and South America.

Cell 2018 11 8;175(5):1185-1197.e22. Epub 2018 Nov 8.

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2018.10.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327247PMC
November 2018

The promise of discovering population-specific disease-associated genes in South Asia.

Nat Genet 2017 Sep 17;49(9):1403-1407. Epub 2017 Jul 17.

CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.

The more than 1.5 billion people who live in South Asia are correctly viewed not as a single large population but as many small endogamous groups. We assembled genome-wide data from over 2,800 individuals from over 260 distinct South Asian groups. We identified 81 unique groups, 14 of which had estimated census sizes of more than 1 million, that descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. We identified multiple examples of recessive diseases in South Asia that are the result of such founder events. This study highlights an underappreciated opportunity for decreasing disease burden among South Asians through discovery of and testing for recessive disease-associated genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675555PMC
September 2017

CLYBL is a polymorphic human enzyme with malate synthase and β-methylmalate synthase activity.

Hum Mol Genet 2014 May 11;23(9):2313-23. Epub 2013 Dec 11.

Department of Molecular Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA.

CLYBL is a human mitochondrial enzyme of unknown function that is found in multiple eukaryotic taxa and conserved to bacteria. The protein is expressed in the mitochondria of all mammalian organs, with highest expression in brown fat and kidney. Approximately 5% of all humans harbor a premature stop polymorphism in CLYBL that has been associated with reduced levels of circulating vitamin B12. Using comparative genomics, we now show that CLYBL is strongly co-expressed with and co-evolved specifically with other components of the mitochondrial B12 pathway. We confirm that the premature stop polymorphism in CLYBL leads to a loss of protein expression. To elucidate the molecular function of CLYBL, we used comparative operon analysis, structural modeling and enzyme kinetics. We report that CLYBL encodes a malate/β-methylmalate synthase, converting glyoxylate and acetyl-CoA to malate, or glyoxylate and propionyl-CoA to β-methylmalate. Malate synthases are best known for their established role in the glyoxylate shunt of plants and lower organisms and are traditionally described as not occurring in humans. The broader role of a malate/β-methylmalate synthase in human physiology and its mechanistic link to vitamin B12 metabolism remain unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddt624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976331PMC
May 2014

Factors influencing the degradation of archival formalin-fixed paraffin-embedded tissue sections.

J Histochem Cytochem 2011 Apr 10;59(4):356-65. Epub 2011 Feb 10.

Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

The loss of antigenicity in archival formalin-fixed paraffin-embedded (FFPE) tissue sections negatively affects both diagnostic histopathology and advanced molecular studies. The mechanisms underlying antigenicity loss in FFPE tissues remain unclear. The authors hypothesize that water is a crucial contributor to protein degradation and decrement of immunoreactivity in FFPE tissues. To test their hypothesis, they examined fixation time, processing time, and humidity of storage environment on protein integrity and antigenicity by immunohistochemistry, Western blotting, and protein extraction. This study revealed that inadequate tissue processing, resulting in retention of endogenous water in tissue sections, results in antigen degradation. Exposure to high humidity during storage results in significant protein degradation and reduced immunoreactivity, and the effects of storage humidity are temperature dependent. Slides stored under vacuum with desiccant do not protect against the effects of residual water from inadequate tissue processing. These results support that the presence of water, both endogenously and exogenously, plays a central role in antigenicity loss. Optimal tissue processing is essential. The parameters of optimal storage of unstained slides remain to be defined, as they are directly affected by preanalytic variables. Nevertheless, minimization of exposure to water is required for antigen preservation in FFPE tissue sections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1369/0022155411398488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201147PMC
April 2011