Publications by authors named "Matthew Mah"

15 Publications

  • Page 1 of 1

Genomic insights into the formation of human populations in East Asia.

Nature 2021 Mar 22;591(7850):413-419. Epub 2021 Feb 22.

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria.

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.
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http://dx.doi.org/10.1038/s41586-021-03336-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993749PMC
March 2021

A minimally destructive protocol for DNA extraction from ancient teeth.

Genome Res 2021 Mar 12;31(3):472-483. Epub 2021 Feb 12.

Institute of Archaeology, Research Centre for the Humanities, 1097 Budapest, Hungary.

Ancient DNA sampling methods-although optimized for efficient DNA extraction-are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth. As the field of ancient DNA has grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained. Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but destructive sampling methods of the cementum often result in the loss of at least one entire root. Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots. This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating. We extracted and sequenced ancient DNA from 30 teeth (and nine corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method. We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes. Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods.
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http://dx.doi.org/10.1101/gr.267534.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919446PMC
March 2021

A genetic history of the pre-contact Caribbean.

Nature 2021 02 23;590(7844):103-110. Epub 2020 Dec 23.

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

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500-1,500 and a maximum of 1,530-8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large. Confirming a small and interconnected Ceramic Age population, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world.
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http://dx.doi.org/10.1038/s41586-020-03053-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864882PMC
February 2021

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

The Genomic History of the Bronze Age Southern Levant.

Cell 2020 05;181(5):1146-1157.e11

Department of Statistics, The Hebrew University of Jerusalem, Jerusalem 9190501, Israel.

We report genome-wide DNA data for 73 individuals from five archaeological sites across the Bronze and Iron Ages Southern Levant. These individuals, who share the "Canaanite" material culture, can be modeled as descending from two sources: (1) earlier local Neolithic populations and (2) populations related to the Chalcolithic Zagros or the Bronze Age Caucasus. The non-local contribution increased over time, as evinced by three outliers who can be modeled as descendants of recent migrants. We show evidence that different "Canaanite" groups genetically resemble each other more than other populations. We find that Levant-related modern populations typically have substantial ancestry coming from populations related to the Chalcolithic Zagros and the Bronze Age Southern Levant. These groups also harbor ancestry from sources we cannot fully model with the available data, highlighting the critical role of post-Bronze-Age migrations into the region over the past 3,000 years.
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http://dx.doi.org/10.1016/j.cell.2020.04.024DOI Listing
May 2020

Human auditory ossicles as an alternative optimal source of ancient DNA.

Genome Res 2020 03 25;30(3):427-436. Epub 2020 Feb 25.

Institute of Archaeological Sciences, Eötvös Loránd University, H-1088 Budapest, Hungary.

DNA recovery from ancient human remains has revolutionized our ability to reconstruct the genetic landscape of the past. Ancient DNA research has benefited from the identification of skeletal elements, such as the cochlear part of the osseous inner ear, that provides optimal contexts for DNA preservation; however, the rich genetic information obtained from the cochlea must be counterbalanced against the loss of morphological information caused by its sampling. Motivated by similarities in developmental processes and histological properties between the cochlea and auditory ossicles, we evaluate the ossicles as an alternative source of ancient DNA. We show that ossicles perform comparably to the cochlea in terms of DNA recovery, finding no substantial reduction in data quantity and minimal differences in data quality across preservation conditions. Ossicles can be sampled from intact skulls or disarticulated petrous bones without damage to surrounding bone, and we argue that they should be used when available to reduce damage to human remains. Our results identify another optimal skeletal element for ancient DNA analysis and add to a growing toolkit of sampling methods that help to better preserve skeletal remains for future research while maximizing the likelihood that ancient DNA analysis will produce useable results.
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http://dx.doi.org/10.1101/gr.260141.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111520PMC
March 2020

The spread of steppe and Iranian-related ancestry in the islands of the western Mediterranean.

Nat Ecol Evol 2020 03 24;4(3):334-345. Epub 2020 Feb 24.

Instituto Internacional de Investigaciones Prehistóricas de Cantabria, Universidad de Cantabria-Gobierno de Cantabria-Banco Santander, Santander, Spain.

Steppe-pastoralist-related ancestry reached Central Europe by at least 2500 BC, whereas Iranian farmer-related ancestry was present in Aegean Europe by at least 1900 BC. However, the spread of these ancestries into the western Mediterranean, where they have contributed to many populations that live today, remains poorly understood. Here, we generated genome-wide ancient-DNA data from the Balearic Islands, Sicily and Sardinia, increasing the number of individuals with reported data from 5 to 66. The oldest individual from the Balearic Islands (~2400 BC) carried ancestry from steppe pastoralists that probably derived from west-to-east migration from Iberia, although two later Balearic individuals had less ancestry from steppe pastoralists. In Sicily, steppe pastoralist ancestry arrived by ~2200 BC, in part from Iberia; Iranian-related ancestry arrived by the mid-second millennium BC, contemporary to its previously documented spread to the Aegean; and there was large-scale population replacement after the Bronze Age. In Sardinia, nearly all ancestry derived from the island's early farmers until the first millennium BC, with the exception of an outlier from the third millennium BC, who had primarily North African ancestry and who-along with an approximately contemporary Iberian-documents widespread Africa-to-Europe gene flow in the Chalcolithic. Major immigration into Sardinia began in the first millennium BC and, at present, no more than 56-62% of Sardinian ancestry is from its first farmers. This value is lower than previous estimates, highlighting that Sardinia, similar to every other region in Europe, has been a stage for major movement and mixtures of people.
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http://dx.doi.org/10.1038/s41559-020-1102-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080320PMC
March 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.
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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.

Science 2019 09;365(6457)

Earth Institute, University College Dublin, Dublin 4, Ireland.

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

Ancient DNA reveals a multistep spread of the first herders into sub-Saharan Africa.

Science 2019 07 30;365(6448). Epub 2019 May 30.

Department of Anthropology, California State University, San Bernardino, CA 92407, USA.

How food production first entered eastern Africa ~5000 years ago and the extent to which people moved with livestock is unclear. We present genome-wide data from 41 individuals associated with Later Stone Age, Pastoral Neolithic (PN), and Iron Age contexts in what are now Kenya and Tanzania to examine the genetic impacts of the spreads of herding and farming. Our results support a multiphase model in which admixture between northeastern African-related peoples and eastern African foragers formed multiple pastoralist groups, including a genetically homogeneous PN cluster. Additional admixture with northeastern and western African-related groups occurred by the Iron Age. These findings support several movements of food producers while rejecting models of minimal admixture with foragers and of genetic differentiation between makers of distinct PN artifacts.
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http://dx.doi.org/10.1126/science.aaw6275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827346PMC
July 2019

The genomic history of the Iberian Peninsula over the past 8000 years.

Science 2019 03;363(6432):1230-1234

Departamento de Prehistoria e Historia Antigua, Universidad Nacional de Educación a Distancia, Valencia, Spain.

We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula. We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming. We reveal sporadic contacts between Iberia and North Africa by ~2500 BCE and, by ~2000 BCE, the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with Steppe ancestry. We show that, in the Iron Age, Steppe ancestry had spread not only into Indo-European-speaking regions but also into non-Indo-European-speaking ones, and we reveal that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia. Additionally, we document how, beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean.
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http://dx.doi.org/10.1126/science.aav4040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436108PMC
March 2019

Cytoreductive surgery and heated intraperitoneal chemotherapy for peritoneal carcinomatosis from rare etiologies.

Am J Surg 2019 05 25;217(5):923-927. Epub 2019 Jan 25.

Department of Surgery and Oncology, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Background: Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) are commonly used in the treatment of peritoneal carcinomatosis (PC) originating from colorectal, appendiceal and ovarian cancers. It is unclear what benefit CRS/HIPEC might have for PC from uncommon etiologies, therefore we sought to describe local practice patterns and evaluate overall survival (OS).

Methods: All patients who had CRS/HIPEC between 2000 and 2016 were identified using our institutional cancer database. Patients with appendiceal, colorectal, and ovarian pathologies were excluded. Kaplan-Meier curves were used to estimate and demonstrate 5-year OS. Cox regression analysis was performed to determine factors associated with OS.

Results: Of all patients treated with CRS/HIPEC at our institution, 38 were treated for PC of rare origin. Etiologies included 23 patients with mesothelioma, 8 with primary peritoneal carcinoma, 4 with small bowel tumours and 3 with gastric cancer. Median OS of 35.4, 20.8, 25.4, and 20.2 months were obtained for each group respectively. 5-year OS for each pathology was 8.7%, 0.0%, 25.0%, and 33.3% respectively with corresponding mean PCI of 31.3, 23.6, 21.5, and 12.7. No independent prognostic factors were significant on Cox regression analysis. Median length of stay was 19 days. Readmission rate within 30 days of discharge was 7.9%. Rate of Grade III/IV complications was 34.2%. No thirty-day mortality.

Conclusion: Survivals beyond 20 months can be obtained with the use of CRS/HIPEC for rare PC etiologies aligning with results of other groups. CRS/HIPEC in well-selected patients demonstrates a clinical benefit and this could be confirmed with a multi-institutional study.
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http://dx.doi.org/10.1016/j.amjsurg.2019.01.011DOI Listing
May 2019

Characterization of the role of EGF-A of low density lipoprotein receptor in PCSK9 binding.

J Lipid Res 2013 Dec 8;54(12):3345-57. Epub 2013 Oct 8.

Departments of Pediatrics and Biochemistry, Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.

Proprotein convertase subtilisin kexin-like 9 (PCSK9) promotes the degradation of low density lipoprotein receptor (LDLR) and plays an important role in regulating plasma LDL-cholesterol levels. We have shown that the epidermal growth factor precursor homology domain A (EGF-A) of the LDLR is critical for PCSK9 binding at the cell surface (pH 7.4). Here, we further characterized the role of EGF-A in binding of PCSK9 to the LDLR. We found that PCSK9 efficiently bound to the LDLR but not to other LDLR family members. Replacement of EGF-A in the very low density lipoprotein receptor (VLDLR) with EGF-A of the LDLR promoted the degradation of the mutant VLDLR induced by PCSK9. Furthermore, we found that PCSK9 bound to recombinant EGF-A in a pH-dependent manner with stronger binding at pH 6.0. We also identified amino acid residues in EGF-A of the LDLR important for PCSK9 binding. Mutations G293H, D299V, L318D, and L318H reduced PCSK9 binding to the LDLR at neutral pH without effect at pH 6.0, while mutations R329P and E332G reduced PCSK9 binding at both pH values. Thus, our findings reveal that EGF-A of the LDLR is critical for PCSK9 binding at the cell surface (neutral pH) and at the acidic endosomal environment (pH 6.0), but different determinants contribute to efficient PCSK9 binding in different pH environments.
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http://dx.doi.org/10.1194/jlr.M041129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826682PMC
December 2013

Application of motion analysis system in pre-impact fall detection.

J Biomech 2008 Jul 26;41(10):2297-304. Epub 2008 Jun 26.

Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore.

The purpose of this study is to investigate unique features of body segments in fall and activities of daily living (ADL) to make automatic detection of fall in its descending phase before the impact. Thus, fall-related injuries can be prevented or reduced by deploying feedback systems before the impact. In this study, the authors propose the following hypothesis: (1) thigh segment normally does not go beyond certain threshold angle to forward and sideways directions in ADL and (2) even if it does, the angular characteristics measured at torso and thigh differ from one another in ADL whereas in the case of fall, they become congruent. These two factors can be used to distinguish fall from ADL in its inception. Vicon 3-D motion analysis system was used in this study. High level of correlation between thigh and torso segments (corr > 0.99) was found for fall activities and low correlation coefficients (mean corr for lateral movements is 0.2338 and for sagittal movements is -0.665) were observed in ADL. By applying the hypothesis, all simulated falls could be detected with no false alarms and around 700ms lead-time before the impact was achieved in pre-impact fall detection. It is the longest lead-time obtained so far in pre-impact fall detection.
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http://dx.doi.org/10.1016/j.jbiomech.2008.03.042DOI Listing
July 2008